1) This document provides guidelines from the American Association for the Study of Liver Diseases (AASLD) and the American College of Gastroenterology on alcoholic liver disease (ALD).
2) It discusses the disease spectrum of ALD, which ranges from fatty liver to cirrhosis. Alcoholic hepatitis is a severe form of ALD with a poor short-term prognosis.
3) Risk factors that influence the development and progression of ALD are identified, including the amount of alcohol consumed, drinking patterns, sex, ethnicity, and nutritional status.
This document provides guidelines for diagnosing and treating alcoholic liver disease (ALD). It discusses the prevalence and natural history of ALD, noting that it ranges from fatty liver to cirrhosis. While the exact prevalence is unknown, an estimated 7.4% of US adults meet criteria for alcohol abuse or dependence. The population risk for ALD mortality relates to national per capita alcohol consumption. The guidelines classify recommendations by class (benefit vs risk) and level (strength of evidence).
This document provides guidelines for the diagnosis and management of autoimmune hepatitis from the American Association for the Study of Liver Diseases (AASLD).
1. Autoimmune hepatitis is a chronic inflammatory liver disease of unknown cause, affecting more women than men. Left untreated, it can lead to cirrhosis and liver failure.
2. The guidelines provide criteria for the diagnosis of definite or probable autoimmune hepatitis based on clinical features, laboratory tests, histology, and serology. Scoring systems are also described to aid in diagnosis.
3. Recommendations are given for treatment with immunosuppressive medications such as prednisone and azathioprine, which can improve symptoms and prevent disease progression
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, costs and patient lifestyle.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, and costs.
This document provides guidelines from the European Association for the Study of the Liver (EASL) on nutrition in chronic liver disease. It finds that malnutrition is frequently a problem for patients with liver cirrhosis and is associated with worse outcomes. All patients with advanced chronic liver disease, especially those with decompensated cirrhosis, should undergo nutritional screening. Those at risk of malnutrition based on the screening should receive a detailed nutritional assessment. The guidelines recommend assessing muscle mass, using global assessment tools, and performing a dietary intake evaluation for those found to be malnourished or at risk. They provide recommendations on nutritional management and screening in specific situations like hepatic encephalopathy or before and after liver transplantation.
This guideline presents recommendations for the management of acute pancreatitis (AP). Key recommendations include: assessing hemodynamic status upon presentation and providing resuscitation as needed; admitting patients with organ failure to intensive care; providing aggressive intravenous hydration within the first 12-24 hours; using ERCP within 24 hours for patients with AP and cholangitis; not routinely using prophylactic antibiotics for severe AP or sterile necrosis; considering infected necrosis in patients not improving after 7-10 days and using antibiotics known to penetrate pancreatic necrosis; and providing enteral nutrition for severe AP to prevent infectious complications while avoiding parenteral nutrition.
This document presents standards of care for diabetes from the American Diabetes Association. It discusses:
1) The classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) The diagnostic criteria for diabetes, which can now include an A1C level of ≥6.5% in addition to fasting plasma glucose and oral glucose tolerance test thresholds.
3) Categories of increased risk for diabetes, called prediabetes, which include impaired fasting glucose, impaired glucose tolerance, and an A1C of 5.7-6.4%.
This document provides an updated practice guideline from the American Association for the Study of Liver Diseases (AASLD) for the treatment of genotype 1 chronic hepatitis C virus infection. The guideline is based on a formal review of recent literature and considers new direct-acting antiviral agents and genetic markers associated with treatment response. Major advances since the previous guideline include the development of direct-acting antiviral protease inhibitors and identification of single-nucleotide polymorphisms related to hepatitis C virus clearance. The guideline provides recommendations for treating genotype 1 infection with current standard of care therapies as well as newer protease inhibitor regimens, noting that additional data is still needed as treatments continue to evolve.
This document provides guidelines for diagnosing and treating alcoholic liver disease (ALD). It discusses the prevalence and natural history of ALD, noting that it ranges from fatty liver to cirrhosis. While the exact prevalence is unknown, an estimated 7.4% of US adults meet criteria for alcohol abuse or dependence. The population risk for ALD mortality relates to national per capita alcohol consumption. The guidelines classify recommendations by class (benefit vs risk) and level (strength of evidence).
This document provides guidelines for the diagnosis and management of autoimmune hepatitis from the American Association for the Study of Liver Diseases (AASLD).
1. Autoimmune hepatitis is a chronic inflammatory liver disease of unknown cause, affecting more women than men. Left untreated, it can lead to cirrhosis and liver failure.
2. The guidelines provide criteria for the diagnosis of definite or probable autoimmune hepatitis based on clinical features, laboratory tests, histology, and serology. Scoring systems are also described to aid in diagnosis.
3. Recommendations are given for treatment with immunosuppressive medications such as prednisone and azathioprine, which can improve symptoms and prevent disease progression
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, costs and patient lifestyle.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, and costs.
This document provides guidelines from the European Association for the Study of the Liver (EASL) on nutrition in chronic liver disease. It finds that malnutrition is frequently a problem for patients with liver cirrhosis and is associated with worse outcomes. All patients with advanced chronic liver disease, especially those with decompensated cirrhosis, should undergo nutritional screening. Those at risk of malnutrition based on the screening should receive a detailed nutritional assessment. The guidelines recommend assessing muscle mass, using global assessment tools, and performing a dietary intake evaluation for those found to be malnourished or at risk. They provide recommendations on nutritional management and screening in specific situations like hepatic encephalopathy or before and after liver transplantation.
This guideline presents recommendations for the management of acute pancreatitis (AP). Key recommendations include: assessing hemodynamic status upon presentation and providing resuscitation as needed; admitting patients with organ failure to intensive care; providing aggressive intravenous hydration within the first 12-24 hours; using ERCP within 24 hours for patients with AP and cholangitis; not routinely using prophylactic antibiotics for severe AP or sterile necrosis; considering infected necrosis in patients not improving after 7-10 days and using antibiotics known to penetrate pancreatic necrosis; and providing enteral nutrition for severe AP to prevent infectious complications while avoiding parenteral nutrition.
This document presents standards of care for diabetes from the American Diabetes Association. It discusses:
1) The classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) The diagnostic criteria for diabetes, which can now include an A1C level of ≥6.5% in addition to fasting plasma glucose and oral glucose tolerance test thresholds.
3) Categories of increased risk for diabetes, called prediabetes, which include impaired fasting glucose, impaired glucose tolerance, and an A1C of 5.7-6.4%.
This document provides an updated practice guideline from the American Association for the Study of Liver Diseases (AASLD) for the treatment of genotype 1 chronic hepatitis C virus infection. The guideline is based on a formal review of recent literature and considers new direct-acting antiviral agents and genetic markers associated with treatment response. Major advances since the previous guideline include the development of direct-acting antiviral protease inhibitors and identification of single-nucleotide polymorphisms related to hepatitis C virus clearance. The guideline provides recommendations for treating genotype 1 infection with current standard of care therapies as well as newer protease inhibitor regimens, noting that additional data is still needed as treatments continue to evolve.
1. This document provides guidelines for the diagnosis, management, and treatment of hepatitis C virus (HCV) infection based on a formal review of recent literature and expert consensus.
2. It recommends screening high-risk groups for HCV infection, including current and former injection drug users, those with HIV, and prior blood transfusion recipients.
3. It also provides guidance on counseling HCV-infected individuals, including advising them to avoid behaviors that may spread the virus and informing them that properly performed tattooing and piercing pose a very low risk of transmission.
This document provides guidelines from the American Diabetes Association for the standards of medical care in diabetes. It discusses the classification and diagnosis of diabetes, including the criteria for diagnosing diabetes based on A1C, fasting plasma glucose, and oral glucose tolerance tests. It also defines categories of increased risk for diabetes, also known as prediabetes. The guidelines are intended to provide clinicians, patients, and others with the components of diabetes care and treatment goals.
Dexamethasone is a corticosteroid that has shown promise in improving outcomes for patients with bacterial meningitis. However, previous studies have found conflicting results on whether it benefits all patients or only certain subgroups. This study conducted a meta-analysis of individual patient data from 5 randomized controlled trials involving 2029 patients to identify which patients are most likely to benefit from dexamethasone treatment. The analysis found that dexamethasone did not significantly reduce death rates or neurological disability overall. It also did not provide significant benefits within any prespecified subgroups based on factors like causative organism, pre-treatment with antibiotics, HIV status, or age. The only benefit seen was a reduction in hearing loss among survivors.
This document presents standards of care for diabetes established by the American Diabetes Association (ADA). It discusses:
1) Classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) Diagnosis of diabetes based on plasma glucose criteria or A1C levels, with a revised grading system to evaluate evidence supporting each recommendation.
3) Screening, diagnostic, and treatment recommendations to improve health outcomes for patients with diabetes.
This study investigated hypocalcemia in patients with acute gastroenteritis at Liaquat University Hospital in Hyderabad, Pakistan. The study included 66 patients with acute gastroenteritis and 66 healthy control subjects. The mean serum calcium level was significantly lower in patients with acute gastroenteritis (6.8455 ± 1.8266 mg/dL) compared to the control group (9.2167 ± 0.4534 mg/dL). Hypocalcemia was observed in 62 (94%) of gastroenteritis patients but only 13 (20%) of controls. The results demonstrated that low serum calcium or hypocalcemia is common in patients with acute gastroenteritis.
This document provides guidelines for the classification, diagnosis, and testing of diabetes and pre-diabetes. It discusses:
1) The classification of diabetes into types 1, 2, gestational, and other specific types.
2) Current diagnostic criteria including A1C, fasting plasma glucose, and oral glucose tolerance tests.
3) Recommendations for testing asymptomatic individuals for pre-diabetes and type 2 diabetes based on risk factors.
This study analyzed clinical outcomes of treated and untreated patients with hepatitis C virus (HCV) infection in two cohorts. It found that HCV patients who did not respond to interferon-alpha based treatment had a significantly increased risk of developing cirrhosis compared to untreated patients, even after adjusting for factors like fibrosis stage and psychosocial risks. Specifically, treatment nonresponders had a 2.35 times higher hazard of cirrhosis in the Veterans Affairs cohort and a 5.9 times higher hazard in the University Hospital cohort compared to untreated patients. However, the overall survival of nonresponders was not significantly different than untreated patients. This suggests that while interferon-alpha treatment failure may accelerate liver fibrosis, it does not necessarily impact overall
This document summarizes the process used to develop a new definition and clinical criteria for identifying septic shock in adults. A task force conducted a systematic review of existing studies, a Delphi consensus process, and analysis of large clinical databases. Based on these analyses, the task force agreed on a new definition of septic shock and identified hypotension requiring vasopressors and an elevated serum lactate level as criteria for identifying adult patients with septic shock. These criteria were validated in separate clinical databases and shown to identify a patient group with significantly higher mortality compared to other commonly reported definitions of septic shock.
These 2012 recommendations update the 2008 American College of Rheumatology guidelines for treating rheumatoid arthritis. The updates include: expanded indications for disease-modifying antirheumatic drugs and biologic agents; guidance on switching between therapies; screening patients starting biologics for tuberculosis reactivation; and use of biologics in patients with hepatitis, congestive heart failure, or malignancy. The recommendations aim to provide guidance for clinicians based on the latest evidence.
Five medical societies from North America, Europe, and Asia have released clinical practice guidelines since 2006 that largely agree intensive hemodialysis should be considered for patients with:
- Large weight gains between treatments
- High rates of fluid removal during treatments
- Poorly controlled blood pressure
- Difficulty achieving their dry weight
- Poor control of minerals like phosphorus or potassium
The guidelines indicate intensive hemodialysis may help patients with these issues by providing more frequent or longer hemodialysis sessions. Physician judgment is also important when determining if intensive hemodialysis is appropriate for a given patient.
This document provides a 3-sentence summary of the consensus statement on the comprehensive type 2 diabetes management algorithm:
The consensus statement presents an updated algorithm for the comprehensive management of type 2 diabetes that incorporates new therapies, management approaches, and clinical data. The algorithm is intended to guide clinicians in developing individualized treatment plans considering a patient's risks, complications, and preferences. It addresses lifestyle therapy, obesity, prediabetes, glucose control, hypertension management, dyslipidemia management, and the attributes and principles for selecting antihyperglycemic therapies.
Circulation 2015-criterios de jones reviewgisa_legal
This document revises the Jones criteria for diagnosing acute rheumatic fever to better align with current evidence and international guidelines. It recognizes that acute rheumatic fever remains a serious health problem globally. The revisions define high-risk populations, acknowledge variability in clinical presentation among these groups, and include Doppler echocardiography as a tool for diagnosing cardiac involvement even without overt symptoms. This represents the first major revision to the Jones criteria by the American Heart Association in over 20 years and applies their classification system for recommendations and evidence levels.
Multiple Chemical Sensitivity & Chronic Fatigue Syndrome in British Gulf War ...v2zq
Multiple Chemical Sensitivity & Chronic Fatigue Syndrome in British Gulf War Veterans - Resources for Healthy Children www.scribd.com/doc/254613619 - For more information, Please see Organic Edible Schoolyards & Gardening with Children www.scribd.com/doc/254613963 - Gardening with Volcanic Rock Dust www.scribd.com/doc/254613846 - Double Food Production from your School Garden with Organic Tech www.scribd.com/doc/254613765 - Free School Gardening Art Posters www.scribd.com/doc/254613694 - Increase Food Production with Companion Planting in your School Garden www.scribd.com/doc/254609890 - Healthy Foods Dramatically Improves Student Academic Success www.scribd.com/doc/254613619 - City Chickens for your Organic School Garden www.scribd.com/doc/254613553 - Huerto Ecológico, Tecnologías Sostenibles, Agricultura Organica www.scribd.com/doc/254613494 - Simple Square Foot Gardening for Schools - Teacher Guide www.scribd.com/doc/254613410 - Free Organic Gardening Publications www.scribd.com/doc/254609890 ~
An 8-week regimen of sofosbuvir plus ledipasvir was found to be effective for many hepatitis C patients in real-world studies, even those who did not meet the official criteria for the shortened treatment. A review of five real-world studies involving over 600 patients found sustained viral response rates of 97% or higher with the 8-week regimen. The results provide reassurance that clinical trial results translate to real-world practice and suggest the criteria for the 8-week regimen could be expanded.
The document provides guidelines for the management of sepsis and septic shock in adults from the Surviving Sepsis Campaign. It recommends that hospitals use a performance improvement program including sepsis screening and standard operating procedures. It recommends against using qSOFA alone as a screening tool due to low sensitivity. It suggests measuring blood lactate in adults suspected of sepsis to help identify those at higher risk of poor outcomes.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, and costs.
Circulation 2015-criterios de jones reviewgisa_legal
This document revises the Jones criteria for diagnosing acute rheumatic fever to better align with current evidence and international guidelines. It recognizes that acute rheumatic fever remains a serious health problem globally. The revisions define high-risk populations, acknowledge variability in clinical presentation among these groups, and include Doppler echocardiography as a tool for diagnosing cardiac involvement even without overt symptoms. This represents the first major revision to the Jones criteria by the American Heart Association in over 20 years and applies their classification system for recommendations and evidence levels.
This document provides guidelines from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) on the management of hyperglycemia in type 2 diabetes. It advocates for a patient-centered approach that considers individual patient factors and preferences. The guidelines acknowledge the heterogeneous nature of type 2 diabetes and recommend treatment be tailored based on a patient's needs, values, and specific disease factors. The guidelines emphasize engaging patients in shared decision-making and pursuing glycemic control through a multifactorial approach that addresses cardiovascular risk factors in addition to blood glucose levels.
This document provides guidelines for the management of acute pancreatitis (AP). It summarizes key recommendations regarding the diagnosis, etiology, risk stratification, and management of AP. The diagnosis of AP is usually established by abdominal pain and elevated serum amylase and/or lipase levels. Contrast-enhanced CT or MRI is only recommended if the diagnosis is unclear or the patient fails to improve. Patients should be stratified based on the presence of organ failure or systemic inflammatory response syndrome and those with organ failure admitted to intensive care. Aggressive intravenous hydration within the first 24 hours and assessment of fluid status is important. Guidelines are also provided for managing gallstone pancreatitis, infectious complications, and interventions.
This document provides an updated clinical practice guideline from the American Society of Clinical Oncology and the American Society of Hematology on the use of erythropoiesis-stimulating agents (ESAs) in adult patients with cancer. The guideline committee reviewed new data published between 2007 and 2010. For patients with chemotherapy-induced anemia and a hemoglobin level under 10g/dL, the committee recommends discussing the potential harms and benefits of ESAs or red blood cell transfusions with patients. The risks and benefits of each option should contribute to shared decisions. The committee cautions against ESA use in other circumstances and provides other recommendations, such as administering ESAs at the lowest effective dose.
This document presents standards of care for diabetes established by the American Diabetes Association (ADA). It discusses:
1) Classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) Diagnosis of diabetes based on plasma glucose criteria or A1C levels, with a revised grading system to evaluate evidence supporting each recommendation.
3) Screening, diagnostic, and treatment recommendations to improve health outcomes for patients with diabetes.
1. This document provides guidelines for the diagnosis, management, and treatment of hepatitis C virus (HCV) infection based on a formal review of recent literature and expert consensus.
2. It recommends screening high-risk groups for HCV infection, including current and former injection drug users, those with HIV, and prior blood transfusion recipients.
3. It also provides guidance on counseling HCV-infected individuals, including advising them to avoid behaviors that may spread the virus and informing them that properly performed tattooing and piercing pose a very low risk of transmission.
This document provides guidelines from the American Diabetes Association for the standards of medical care in diabetes. It discusses the classification and diagnosis of diabetes, including the criteria for diagnosing diabetes based on A1C, fasting plasma glucose, and oral glucose tolerance tests. It also defines categories of increased risk for diabetes, also known as prediabetes. The guidelines are intended to provide clinicians, patients, and others with the components of diabetes care and treatment goals.
Dexamethasone is a corticosteroid that has shown promise in improving outcomes for patients with bacterial meningitis. However, previous studies have found conflicting results on whether it benefits all patients or only certain subgroups. This study conducted a meta-analysis of individual patient data from 5 randomized controlled trials involving 2029 patients to identify which patients are most likely to benefit from dexamethasone treatment. The analysis found that dexamethasone did not significantly reduce death rates or neurological disability overall. It also did not provide significant benefits within any prespecified subgroups based on factors like causative organism, pre-treatment with antibiotics, HIV status, or age. The only benefit seen was a reduction in hearing loss among survivors.
This document presents standards of care for diabetes established by the American Diabetes Association (ADA). It discusses:
1) Classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) Diagnosis of diabetes based on plasma glucose criteria or A1C levels, with a revised grading system to evaluate evidence supporting each recommendation.
3) Screening, diagnostic, and treatment recommendations to improve health outcomes for patients with diabetes.
This study investigated hypocalcemia in patients with acute gastroenteritis at Liaquat University Hospital in Hyderabad, Pakistan. The study included 66 patients with acute gastroenteritis and 66 healthy control subjects. The mean serum calcium level was significantly lower in patients with acute gastroenteritis (6.8455 ± 1.8266 mg/dL) compared to the control group (9.2167 ± 0.4534 mg/dL). Hypocalcemia was observed in 62 (94%) of gastroenteritis patients but only 13 (20%) of controls. The results demonstrated that low serum calcium or hypocalcemia is common in patients with acute gastroenteritis.
This document provides guidelines for the classification, diagnosis, and testing of diabetes and pre-diabetes. It discusses:
1) The classification of diabetes into types 1, 2, gestational, and other specific types.
2) Current diagnostic criteria including A1C, fasting plasma glucose, and oral glucose tolerance tests.
3) Recommendations for testing asymptomatic individuals for pre-diabetes and type 2 diabetes based on risk factors.
This study analyzed clinical outcomes of treated and untreated patients with hepatitis C virus (HCV) infection in two cohorts. It found that HCV patients who did not respond to interferon-alpha based treatment had a significantly increased risk of developing cirrhosis compared to untreated patients, even after adjusting for factors like fibrosis stage and psychosocial risks. Specifically, treatment nonresponders had a 2.35 times higher hazard of cirrhosis in the Veterans Affairs cohort and a 5.9 times higher hazard in the University Hospital cohort compared to untreated patients. However, the overall survival of nonresponders was not significantly different than untreated patients. This suggests that while interferon-alpha treatment failure may accelerate liver fibrosis, it does not necessarily impact overall
This document summarizes the process used to develop a new definition and clinical criteria for identifying septic shock in adults. A task force conducted a systematic review of existing studies, a Delphi consensus process, and analysis of large clinical databases. Based on these analyses, the task force agreed on a new definition of septic shock and identified hypotension requiring vasopressors and an elevated serum lactate level as criteria for identifying adult patients with septic shock. These criteria were validated in separate clinical databases and shown to identify a patient group with significantly higher mortality compared to other commonly reported definitions of septic shock.
These 2012 recommendations update the 2008 American College of Rheumatology guidelines for treating rheumatoid arthritis. The updates include: expanded indications for disease-modifying antirheumatic drugs and biologic agents; guidance on switching between therapies; screening patients starting biologics for tuberculosis reactivation; and use of biologics in patients with hepatitis, congestive heart failure, or malignancy. The recommendations aim to provide guidance for clinicians based on the latest evidence.
Five medical societies from North America, Europe, and Asia have released clinical practice guidelines since 2006 that largely agree intensive hemodialysis should be considered for patients with:
- Large weight gains between treatments
- High rates of fluid removal during treatments
- Poorly controlled blood pressure
- Difficulty achieving their dry weight
- Poor control of minerals like phosphorus or potassium
The guidelines indicate intensive hemodialysis may help patients with these issues by providing more frequent or longer hemodialysis sessions. Physician judgment is also important when determining if intensive hemodialysis is appropriate for a given patient.
This document provides a 3-sentence summary of the consensus statement on the comprehensive type 2 diabetes management algorithm:
The consensus statement presents an updated algorithm for the comprehensive management of type 2 diabetes that incorporates new therapies, management approaches, and clinical data. The algorithm is intended to guide clinicians in developing individualized treatment plans considering a patient's risks, complications, and preferences. It addresses lifestyle therapy, obesity, prediabetes, glucose control, hypertension management, dyslipidemia management, and the attributes and principles for selecting antihyperglycemic therapies.
Circulation 2015-criterios de jones reviewgisa_legal
This document revises the Jones criteria for diagnosing acute rheumatic fever to better align with current evidence and international guidelines. It recognizes that acute rheumatic fever remains a serious health problem globally. The revisions define high-risk populations, acknowledge variability in clinical presentation among these groups, and include Doppler echocardiography as a tool for diagnosing cardiac involvement even without overt symptoms. This represents the first major revision to the Jones criteria by the American Heart Association in over 20 years and applies their classification system for recommendations and evidence levels.
Multiple Chemical Sensitivity & Chronic Fatigue Syndrome in British Gulf War ...v2zq
Multiple Chemical Sensitivity & Chronic Fatigue Syndrome in British Gulf War Veterans - Resources for Healthy Children www.scribd.com/doc/254613619 - For more information, Please see Organic Edible Schoolyards & Gardening with Children www.scribd.com/doc/254613963 - Gardening with Volcanic Rock Dust www.scribd.com/doc/254613846 - Double Food Production from your School Garden with Organic Tech www.scribd.com/doc/254613765 - Free School Gardening Art Posters www.scribd.com/doc/254613694 - Increase Food Production with Companion Planting in your School Garden www.scribd.com/doc/254609890 - Healthy Foods Dramatically Improves Student Academic Success www.scribd.com/doc/254613619 - City Chickens for your Organic School Garden www.scribd.com/doc/254613553 - Huerto Ecológico, Tecnologías Sostenibles, Agricultura Organica www.scribd.com/doc/254613494 - Simple Square Foot Gardening for Schools - Teacher Guide www.scribd.com/doc/254613410 - Free Organic Gardening Publications www.scribd.com/doc/254609890 ~
An 8-week regimen of sofosbuvir plus ledipasvir was found to be effective for many hepatitis C patients in real-world studies, even those who did not meet the official criteria for the shortened treatment. A review of five real-world studies involving over 600 patients found sustained viral response rates of 97% or higher with the 8-week regimen. The results provide reassurance that clinical trial results translate to real-world practice and suggest the criteria for the 8-week regimen could be expanded.
The document provides guidelines for the management of sepsis and septic shock in adults from the Surviving Sepsis Campaign. It recommends that hospitals use a performance improvement program including sepsis screening and standard operating procedures. It recommends against using qSOFA alone as a screening tool due to low sensitivity. It suggests measuring blood lactate in adults suspected of sepsis to help identify those at higher risk of poor outcomes.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, and costs.
Circulation 2015-criterios de jones reviewgisa_legal
This document revises the Jones criteria for diagnosing acute rheumatic fever to better align with current evidence and international guidelines. It recognizes that acute rheumatic fever remains a serious health problem globally. The revisions define high-risk populations, acknowledge variability in clinical presentation among these groups, and include Doppler echocardiography as a tool for diagnosing cardiac involvement even without overt symptoms. This represents the first major revision to the Jones criteria by the American Heart Association in over 20 years and applies their classification system for recommendations and evidence levels.
This document provides guidelines from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) on the management of hyperglycemia in type 2 diabetes. It advocates for a patient-centered approach that considers individual patient factors and preferences. The guidelines acknowledge the heterogeneous nature of type 2 diabetes and recommend treatment be tailored based on a patient's needs, values, and specific disease factors. The guidelines emphasize engaging patients in shared decision-making and pursuing glycemic control through a multifactorial approach that addresses cardiovascular risk factors in addition to blood glucose levels.
This document provides guidelines for the management of acute pancreatitis (AP). It summarizes key recommendations regarding the diagnosis, etiology, risk stratification, and management of AP. The diagnosis of AP is usually established by abdominal pain and elevated serum amylase and/or lipase levels. Contrast-enhanced CT or MRI is only recommended if the diagnosis is unclear or the patient fails to improve. Patients should be stratified based on the presence of organ failure or systemic inflammatory response syndrome and those with organ failure admitted to intensive care. Aggressive intravenous hydration within the first 24 hours and assessment of fluid status is important. Guidelines are also provided for managing gallstone pancreatitis, infectious complications, and interventions.
This document provides an updated clinical practice guideline from the American Society of Clinical Oncology and the American Society of Hematology on the use of erythropoiesis-stimulating agents (ESAs) in adult patients with cancer. The guideline committee reviewed new data published between 2007 and 2010. For patients with chemotherapy-induced anemia and a hemoglobin level under 10g/dL, the committee recommends discussing the potential harms and benefits of ESAs or red blood cell transfusions with patients. The risks and benefits of each option should contribute to shared decisions. The committee cautions against ESA use in other circumstances and provides other recommendations, such as administering ESAs at the lowest effective dose.
This document presents standards of care for diabetes established by the American Diabetes Association (ADA). It discusses:
1) Classification of diabetes into four types: type 1, type 2, other specific types, and gestational diabetes.
2) Diagnosis of diabetes based on plasma glucose criteria or A1C levels, with a revised grading system to evaluate evidence supporting each recommendation.
3) Screening, diagnostic, and treatment recommendations to improve health outcomes for patients with diabetes.
Haochuan Tang
Professor Xiuwu Liu
CHI 253
11/4/2019
Quotation:
Book: Hisa
Chapter 11: The Romance of The Three Kingdoms; Kuan Yu’s downfall and death
Page 48 line 8.
kuan yu's downfall and death are recounted in some of the finest chapters of the novel.an aging warrior, he is reaching the pinnacle of his fame but also exhibiting the most impossible haughtiness and folly.
Question:
What was the purpose of further developing the character even though he was willed with flaws such as his arrogance and irrationality? Acuity to the historical data would be sufficient in the development of Kuan Yu to the reader. The concept of developing a hero escapes the purpose of the narrative; however, it can be speculated that the concept of heroism according to Lo Kuan-chung relies on both historical and folk details.
Week 4: Administration Considerations for
Assessment Tools
Consider the following scenario:
Terrence is considering next steps for a client, Angela, who has come for
therapy at the family counseling center where he works. When Angela
scheduled her appointment on the telephone, she had described her
concerns with marital difficulties, insomnia, and depression. During her first
session, however, Terrence noticed that Angela had a very nervous
demeanor, picked at her skin constantly, and had a rasping cough. When
Terrence asked Angela about her employment, she admitted that she had
lost her job and that her husband was angry about it. She said she was
afraid her husband was on the brink of becoming abusive.
Terrence is not sure what to do first. He suspects Angela might have a
substance addiction, but clearly she has several interlocking problems, and
many are urgent. Should Terrence administer a screening for addiction or a
more general clinical assessment? If he does decide to administer an
addictions assessment, which of the many that are available should he
choose and why?
This week, you differentiate between the use of addictions assessment
tools and clinical assessment tools and review several assessment tools in
order to evaluate one of them.
Screening for
Alcohol Problems
What Makes a Test Effective?
Scott H. Stewart, M.D., and Gerard J. Connors, Ph.D.
Screening tests are useful in a variety of settings and contexts, but not all disorders are
amenable to screening. Alcohol use disorders (AUDs) and other drinking problems are a
major cause of morbidity and mortality and are prevalent in the population; effective
treatments are available, and patient outcome can be improved by early detection and
intervention. Therefore, the use of screening tests to identify people with or at risk for AUDs
can be beneficial. The characteristics of screening tests that influence their usefulness in
clinical settings include their validity, sensitivity, and specificity. Appropriately conducted
screening tests can help clinicians better predict the probability that individual patients do or
do not have ...
This document presents standards of care for diabetes published by the American Diabetes Association. It discusses that diabetes requires ongoing medical care and patient self-management to prevent complications. The standards are intended to provide guidance on treatment goals and quality of care evaluation. The recommendations are based on evidence from screening, diagnostic and therapeutic interventions shown to positively impact health outcomes. The standards are revised annually based on new evidence and committee review.
This document provides guidelines for the diagnosis and treatment of dyslipidemia and prevention of atherosclerosis from the American Association of Clinical Endocrinologists (AACE). It summarizes screening recommendations, risk assessment, and treatment guidelines for various lipid disorders, with special consideration for patients with diabetes, women, and pediatric patients. The guidelines are based on evidence from literature reviews and expert opinion. They are intended to assist endocrinologists in reducing risks and consequences of dyslipidemia by providing a practical guide. The guidelines extend existing guidelines and complement AACE's Diabetes Mellitus Comprehensive Care Plan guidelines.
This document presents standards of care for diabetes published by the American Diabetes Association. It discusses that diabetes requires ongoing medical care and patient self-management to prevent complications. The standards provide clinicians and others components of diabetes care, treatment goals, and ways to evaluate quality of care, while allowing for customization based on individual patient factors. The recommendations are based on evidence from screening, diagnostic and therapeutic interventions shown to positively impact patient health outcomes and be cost-effective.
The Cleveland Clinic Gastrointestinal symptoms in cancer patients with.pdfJaveriana Cali
Gastrointestinal (GI) symptoms are common and detrimental to quality of life in advanced cancer patients. Nausea, vomiting, and diarrhea are prevalent, often caused by medication side effects or the underlying disease. Effective management of GI symptoms requires thorough assessment, evidence-based approaches, and monitoring of both clinical measures and patient-reported outcomes. New drugs and complementary therapies show promise in both symptom management and prevention.
2023 Definitions, phenotypes, and subphenotypes in AKI.pdfJesusPlanelles
The document discusses the need to reclassify acute kidney injury (AKI) to facilitate more targeted and individualized treatment approaches.
Current AKI definitions focus only on functional changes like rises in creatinine, which detect injury too late for early intervention. The document proposes reclassifying AKI based on causal phenotype and subphenotypes defined by biomarkers that reveal specific injury pathways.
Precisely defining AKI phenotypes by cause, such as ischemia or nephrotoxins, and subphenotypes by activated pathophysiological mechanisms, could help triage patients to tailored therapies in a precision medicine approach, rather than just providing supportive care for the broad AKI syndrome.
This document is the February 2015 issue of the UTSW Internal Medicine Journal Watch. It contains summaries of recent articles across various specialties, including endocrinology, rheumatology, health care improvement, general internal medicine, nephrology, infectious diseases, hepatology, and cardiology. There is also an EKG challenge case. The endocrinology section highlights updates to diabetes screening and treatment guidelines from the American Diabetes Association, including changes to blood glucose and blood pressure targets. The health care improvement section discusses a study finding that some health plans are using adverse drug tiering to discourage enrollment by patients with high-cost conditions like HIV.
Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. Get For More Info Visit Us http://www.jcehapatology.com
Future Considerations of Biological Disparities in Drug Development for NAFLD...semualkaira
Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health concern not only in the US but also worldwide due to the
global obesity epidemic. Although the natural course in the majority
of NAFLD patients is relatively benign, those with non-alcoholic
steatohepatitis (NASH) are at an increased risk of disease progression, leading to hepatic fibrosis, cirrhosis, end-stage liver disease
(ESLD), and hepatocellular carcinoma (HCC).
1- Differentiate between primary and secondary sources and provide an.pdfcontact28
1. Differentiate between primary and secondary sources and provide an example for each one. 2.
Describe the similarities and differences between a research paper and a review paper. 4. Is the
following Abstract from a research article? Abstract People of African ancestry (Blacks) have an
increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical
factors. Two variants in the APOL1 gene are now thought to account for much of the racial
disparity associated with hypertensive kidney failure in Blacks. However. this knowledge has not
been translated into clinical care to help improve patient outcomes and address disparities.
GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic
risk information into primary care. Hypertensive, non-diabetic, adults with self-reported African
ancestry. without kidney dysfunction, are recruited from diverse clinical settings and randomized
to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control).
Providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff
return APOL1 results to patients and provide low-literacy educational materials. Real-time
clinical decision support ols alert clinicians of their patients' APOL1 results and associated risk
status at the point of care. Our academiccommunity-clinical partnership designed a study to
generate information about the impact of genetic risk information on patient care (blood pressure
and renal surveillance) and on patient and provider knowledge, attitudes, beliefs, and behaviors.
GUARDD will help establish the effective implementation of APOLL risk-informed
management of hypertensive patients at high risk of CKD, and will provide a robust framework
for future endeavors to implement genomic medicine in diverse clinical practices. It will also add
to the important dialog about factors contributing to and may help eliminate racial disparities in.
kidney disease. True: False 5. Of the 3 titles listed below, which title(s) is suitable for a review
paper: a. Chronic Kidney Disease Diagnosis and Management b. Determining the Effects and
Challenges of Incorporating Genetic Testing into Primary Care Management of Hypertensive
Patients with African Ancestry c. Pharmacist Intervention for Blood Pressure Control in Patients
with Diabetes and/or Chronic Kidney Disease d. all of the above 6. Which reference style is used
for citing electronic journal articles. a. DOI b. APA c. NLM d. MLA e. all of the above f. none of
the above.
C15 ada standards of medical care in diabetes 2012Diabetes for all
This document provides standards of care for diabetes management and treatment. It discusses that diabetes requires ongoing medical care and patient self-management to prevent complications. The standards are intended to guide clinicians and other stakeholders in evaluating quality of care and setting treatment goals, while allowing for flexibility based on individual patient factors. Diagnosis of diabetes can be made based on hemoglobin A1c, fasting plasma glucose, or oral glucose tolerance test results.
This document discusses metabolic syndrome, a cluster of risk factors that increases the risk of cardiovascular disease when associated with insulin resistance. It provides definitions of metabolic syndrome from several major health organizations, which include obesity, dyslipidemia, high blood pressure, and insulin resistance or diabetes as core components. The document emphasizes that regardless of debates around defining metabolic syndrome, patients with multiple risk factors have increased risk of heart disease and should be identified and treated early through preventive healthcare practices and lifestyle changes.
Abstract— Non Alcoholic Fatty Liver Disease is also becoming public health impotance nowadays. So this study was aimed to determine the association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. This study includes a total of 222 subjects were enrolled as per the inclusion/exclusion criteria, out of which 110 cases who had NAFLD with hepatic steatosis on ultrasonography and 112 subjects who did not have NAFLD were considered control. These cases and controls were interrogated and investigated further. Observations were recorded and association of Non Alcoholic Fatty Liver Disease with metabolic syndrome and Cardio-Vascular disease along with assessment of degree of severity of NAFLD with respect to number of components of metabolic syndrome. Statistical methods used were unpaired student’s t-test for continuous variables, Fischer’s and chi-sq test for categorical variables using bivariate analysis by Graph Pad Instat Version 3.10. Risk was assessed in terms of Odd's Ratio. The patients with MS and NAFLD had a higher proportion of CVD compared with those who did not have NAFLD (29.1 vs 18.1 %). This study concludes that NAFLD is significantly associated with MS; most significant with WC, followed by TG and FBS and thus can be considered as hepatic component of MS. This needs more research with large multi-centric prospective studies to evaluate NAFLD as an independent risk factor for CVD.
Similar to Alcoholic liverdisease1 2010[1] - Medicina Interna II (20)
Prevalencia de Alteraciones Electrocardiograficas en Deportistas Profesionale...Matias Fernandez Viña
Este documento resume un estudio sobre la prevalencia de alteraciones electrocardiográficas en deportistas profesionales de un club en San Nicolás, Argentina. El estudio evaluó 124 deportistas de alto rendimiento utilizando electrocardiogramas y encuestas. Encontró que el 59% de los deportistas tenían electrocardiogramas normales, mientras que el 41% mostró alteraciones como bloqueo incompleto de rama derecha (22%), bradicardia sinusal leve (11%) y trastorno de repolarización precoz (10%). Las alteraciones vari
El electrocardiograma (ECG) registra la actividad eléctrica del corazón a través de electrodos colocados en la piel. El ECG proporciona información sobre el ritmo cardíaco, posibles problemas de corazón como infartos o arritmias, y cómo los medicamentos afectan el corazón. Al colocar electrodos en ubicaciones específicas, el ECG puede obtener 12 derivaciones que muestran la actividad eléctrica del corazón desde diferentes ángulos.
La disfagia se refiere a una sensación de atascamiento al pasar los alimentos a través del esófago. Puede ser funcional o orgánica, dependiendo de si es causada por una lesión o alteración funcional. Las causas incluyen enfermedades generales, paraesofágicas o esofágicas. La evaluación incluye el interrogatorio, radiografía esofágica de doble contraste y endoscopia para determinar la causa.
El documento describe la anatomía del corazón. El corazón es un órgano muscular ubicado en el centro del pecho que bombea sangre a través del cuerpo. Tiene cuatro cámaras y cuatro válvulas que controlan el flujo sanguíneo. El sistema de conducción eléctrica coordina las contracciones del corazón.
1) Las náuseas son la sensación de deseo inminente de vomitar y se describen como una sensación desagradable en la garganta y epigastrio. 2) Pueden ser causadas por factores orgánicos como problemas gastrointestinales o fármacos, o factores funcionales como estímulos desagradables o alteraciones emocionales. 3) Los vómitos son la expulsión violenta del contenido gástrico por la boca precedida o no de náuseas, controlados por el centro del vómito en el bulbo raqu
Las bacterias de la familia Mycoplasmataceae son procariotas sin pared celular que son resistentes a antibióticos como los betalactámicos. Incluyen los géneros Mycoplasma y Ureaplasma, que pueden causar infecciones respiratorias y del tracto genital. Mycoplasma pneumoniae causa neumonía atípica transmitida por gotas de Flügge, mientras que Mycoplasma hominis y Ureaplasma urealyticum forman parte de la flora genital asintomática pero pueden caus
El documento resume varias colagenopatías, incluyendo Sjögren, esclerodermia, polimiositis, dermatomiositis, enfermedad mixta del tejido conectivo y vasculitis. Describe los síntomas, criterios de diagnóstico, clasificaciones y opciones de tratamiento para cada una.
La monartritis es una inflamación de una sola articulación que puede ser causada por infecciones, depósitos de cristales o enfermedades autoinmunes. Los síntomas incluyen dolor, hinchazón y calor en la articulación afectada. El diagnóstico se basa en el examen físico, rayos X y análisis del líquido articular. El tratamiento depende de la causa subyacente e incluye antibióticos, drenaje de la articulación y descanso para aliviar la inflamación.
El documento presenta los resultados de una encuesta realizada a 1.958 mujeres con artritis reumatoide en varios países europeos y Estados Unidos. Encontró que la mayoría experimentaba dolor diario a pesar del tratamiento, y que el dolor era un tema importante en las discusiones con sus médicos. Casi un tercio consideraba un "buen día" como uno con alivio rápido del dolor y sin rigidez matutina.
El documento proporciona información sobre las enfermedades de la glándula tiroides. Describe las hormonas producidas por la glándula tiroides, las causas y manifestaciones clínicas del hipotiroidismo y hipertiroidismo, y los valores de laboratorio normales para evaluar las enfermedades tiroideas.
El documento proporciona información sobre el tratamiento de la diabetes. Describe las medidas generales como la educación, dieta, ejercicio y control de factores de riesgo. Explica los tratamientos farmacológicos como la insulina, sulfonilureas, biguanidas, glitazonas y alfa-glucosidasas. También cubre temas como la detección de complicaciones, tipos de insulina y dispositivos de administración.
1) La diabetes es un grupo de trastornos metabólicos caracterizados por la hiperglucemia debido a defectos en la secreción o acción de la insulina.
2) Existen dos tipos principales de diabetes: la tipo 1 causada por destrucción autoinmune de las células beta que producen insulina, y la tipo 2 asociada con resistencia a la insulina.
3) Las complicaciones de la diabetes incluyen problemas cardiovasculares, renales, oculares, neurológicos y de la piel.
Las leucemias y los linfomas son grupos de enfermedades neoplásicas caracterizadas por la proliferación anormal de células de la sangre. Las leucemias involucran las células madre hematopoyéticas en la médula ósea y pueden afectar las series mieloide o linfoide, mientras que los linfomas se originan a partir de los linfocitos B o T. Estas enfermedades pueden causar síntomas como fiebre, hemorragias, infecciones y dolor óseo y su diagnóstico
Las leucemias y los linfomas son grupos de enfermedades neoplásicas caracterizadas por la proliferación anormal de células de la sangre y la médula ósea. Presentan síntomas como fiebre, hemorragias, infecciones y dolor óseo. Su diagnóstico requiere exámenes de sangre y médula ósea para identificar las células anormales. Existen diferentes tipos que varían en su tratamiento y pronóstico.
Las leucemias y los linfomas son grupos de enfermedades neoplásicas caracterizadas por la proliferación anormal de células de la sangre y la médula ósea. Presentan síntomas como fiebre, hemorragias, infecciones y dolor óseo. Su diagnóstico requiere exámenes de sangre y médula ósea para identificar las células anormales. Existen diferentes tipos que varían en su tratamiento y pronóstico.
El documento describe el síndrome purpúrico y los mecanismos de hemostasia primaria y secundaria. Explica cómo evaluar a pacientes con síndrome purpúrico mediante interrogatorio, examen físico y pruebas de laboratorio como recuento de plaquetas, tiempo de sangrado y pruebas de coagulación. También clasifica los tipos de púrpuras y analiza casos clínicos de pacientes con púrpuras trombocitopénicas.
El documento describe diferentes tipos de anemia. Define la anemia y sus manifestaciones clínicas. Explica cómo clasificar las anemias según su causa, como la pérdida de sangre, la disminución de producción o las anemias hemolíticas. Describe en detalle la anemia ferropénica, la anemia megaloblástica, la esferocitosis y otras anemias hemolíticas. Explica los estudios necesarios para diagnosticar cada tipo y los tratamientos correspondientes.
Este documento trata sobre el enfoque del paciente con síndrome anémico. Define la anemia, clasifica los tipos de anemia según su etiología, morfología y otros criterios. Describe las características y causas de las anemias microcíticas, normocíticas y macrocíticas. Explica los exámenes de laboratorio importantes, las manifestaciones clínicas y el enfoque para evaluar y tratar a un paciente con síndrome anémico.
Este documento describe la clasificación y evaluación de la ascitis, así como su tratamiento. La ascitis puede ser no complicada, complicada con infección o síndrome hepatorrenal, o refractaria. La evaluación incluye análisis de sangre, orina y líquido ascítico. El gradiente albúmina sérica-ascítico ayuda a identificar la causa. El tratamiento consiste en restricción de sodio, diuréticos como espironolactona y furosemida, y paracentesis con expansores plasmáticos. La cirugía
El documento describe la cirrosis hepática, una enfermedad crónica del hígado caracterizada por la fibrosis masiva y la formación de nódulos de regeneración. Se clasifica según criterios morfológicos, clínicos y etiológicos. Las causas más frecuentes son el alcoholismo y la hepatitis viral. Los síntomas varían desde leves en la etapa compensada hasta graves complicaciones en la descompensada como hemorragias o insuficiencia hepática. El diagnóstico se realiza mediante análisis de laboratorio, ecografía e hist
A Guide to a Winning Interview June 2024Bruce Bennett
This webinar is an in-depth review of the interview process. Preparation is a key element to acing an interview. Learn the best approaches from the initial phone screen to the face-to-face meeting with the hiring manager. You will hear great answers to several standard questions, including the dreaded “Tell Me About Yourself”.
We recently hosted the much-anticipated Community Skill Builders Workshop during our June online meeting. This event was a culmination of six months of listening to your feedback and crafting solutions to better support your PMI journey. Here’s a look back at what happened and the exciting developments that emerged from our collaborative efforts.
A Gathering of Minds
We were thrilled to see a diverse group of attendees, including local certified PMI trainers and both new and experienced members eager to contribute their perspectives. The workshop was structured into three dynamic discussion sessions, each led by our dedicated membership advocates.
Key Takeaways and Future Directions
The insights and feedback gathered from these discussions were invaluable. Here are some of the key takeaways and the steps we are taking to address them:
• Enhanced Resource Accessibility: We are working on a new, user-friendly resource page that will make it easier for members to access training materials and real-world application guides.
• Structured Mentorship Program: Plans are underway to launch a mentorship program that will connect members with experienced professionals for guidance and support.
• Increased Networking Opportunities: Expect to see more frequent and varied networking events, both virtual and in-person, to help you build connections and foster a sense of community.
Moving Forward
We are committed to turning your feedback into actionable solutions that enhance your PMI journey. This workshop was just the beginning. By actively participating and sharing your experiences, you have helped shape the future of our Chapter’s offerings.
Thank you to everyone who attended and contributed to the success of the Community Skill Builders Workshop. Your engagement and enthusiasm are what make our Chapter strong and vibrant. Stay tuned for updates on the new initiatives and opportunities to get involved. Together, we are building a community that supports and empowers each other on our PMI journeys.
Stay connected, stay engaged, and let’s continue to grow together!
About PMI Silver Spring Chapter
We are a branch of the Project Management Institute. We offer a platform for project management professionals in Silver Spring, MD, and the DC/Baltimore metro area. Monthly meetings facilitate networking, knowledge sharing, and professional development. For more, visit pmissc.org.
Success is often not achievable without facing and overcoming obstacles along the way. To reach our goals and achieve success, it is important to understand and resolve the obstacles that come in our way.
In this article, we will discuss the various obstacles that hinder success, strategies to overcome them, and examples of individuals who have successfully surmounted their obstacles.
In the intricate tapestry of life, connections serve as the vibrant threads that weave together opportunities, experiences, and growth. Whether in personal or professional spheres, the ability to forge meaningful connections opens doors to a multitude of possibilities, propelling individuals toward success and fulfillment.
Eirini is an HR professional with strong passion for technology and semiconductors industry in particular. She started her career as a software recruiter in 2012, and developed an interest for business development, talent enablement and innovation which later got her setting up the concept of Software Community Management in ASML, and to Developer Relations today. She holds a bachelor degree in Lifelong Learning and an MBA specialised in Strategic Human Resources Management. She is a world citizen, having grown up in Greece, she studied and kickstarted her career in The Netherlands and can currently be found in Santa Clara, CA.
Joyce M Sullivan, Founder & CEO of SocMediaFin, Inc. shares her "Five Questions - The Story of You", "Reflections - What Matters to You?" and "The Three Circle Exercise" to guide those evaluating what their next move may be in their careers.
Leadership Ambassador club Adventist modulekakomaeric00
Aims to equip people who aspire to become leaders with good qualities,and with Christian values and morals as per Biblical teachings.The you who aspire to be leaders should first read and understand what the ambassador module for leadership says about leadership and marry that to what the bible says.Christians sh
Learnings from Successful Jobs SearchersBruce Bennett
Are you interested to know what actions help in a job search? This webinar is the summary of several individuals who discussed their job search journey for others to follow. You will learn there are common actions that helped them succeed in their quest for gainful employment.
2. 308 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
Table 1. Grading System for Recommendations estimate worldwide patterns of alcohol consumption and
Classification Description allow comparisons of alcohol related morbidity and mor-
Class I Conditions for which there is evidence and/or general tality.22 The burden of alcohol-related disease is highest in
agreement that a given diagnostic evaluation, the developed world, where it may account for as much as
procedure or treatment is beneficial, useful, and 9.2% of all disability-adjusted life years. Even in develop-
effective.
Class II Conditions for which there is conflicting evidence
ing regions of the world, however, alcohol accounts for a
and/or a divergence of opinion about the major portion of global disease burden, and is projected to
usefulness/efficacy of a diagnostic evaluation, take on increasing importance in those regions over
procedure or treatment.
time.22,23
Class IIa Weight of evidence/opinion is in favor of usefulness/
efficacy.
Class IIb Usefulness/efficacy is less well established by II. Disease Spectrum
evidence/opinion.
Class III Conditions for which there is evidence and/or general The spectrum of alcohol-related liver injury varies
agreement that a diagnostic evaluation/procedure/ from simple steatosis to cirrhosis. These are not necessar-
treatment is not useful/effective and in some
cases may be harmful.
ily distinct stages of evolution of disease, but rather, mul-
tiple stages that may be present simultaneously in a given
Level of Evidence Description
individual.24,25 These are often grouped into three histo-
Level A Data derived from multiple randomized clinical trials logical stages of ALD: fatty liver or simple steatosis, alco-
or meta-analyses.
Level B Data derived from a single randomized trial, or
holic hepatitis, and chronic hepatitis with hepatic fibrosis
nonrandomized studies. or cirrhosis.26 These latter stages may also be associated
Level C Only consensus opinion of experts, case studies, or with a number of histologic changes (which have varying
standard-of-care. degrees of specificity for ALD), including the presence of
Mallory’s hyaline, megamitochondria, or perivenular and
perisinusoidal fibrosis.24
ure to recognize alcoholism remains a significant problem Fatty liver develops in about 90% of individuals who
and impairs efforts at both the prevention and manage- drink more than 60 g/day of alcohol,27 but may also occur
ment of patients with ALD.13,14 Although the exact prev- in individuals who drink less.28 Simple, uncomplicated
alence is unknown, approximately 7.4% of adult fatty liver is usually asymptomatic and self limited, and
Americans were estimated to meet DSM-IV criteria for may be completely reversible with abstinence after about
the diagnosis of alcohol abuse and/or alcohol dependence 4-6 weeks.29 However, several studies have suggested that
in 199415; more recent data suggest 4.65% meet criteria progression to fibrosis and cirrhosis occurs in 5%-15% of
for alcohol abuse and 3.81% for alcohol dependence.16 In patients despite abstinence.30,31 In one study, continued
2003, 44% of all deaths from liver disease were attributed alcohol use ( 40 g/day) increased the risk of progression
to alcohol.17 to cirrhosis to 30%, and fibrosis or cirrhosis to 37%.32
Population level mortality from alcoholic liver disease Fibrosis is believed to start in the perivenular area and
is related to per capita alcohol consumption obtained is influenced by the amount of alcohol ingested.33,34
from national alcoholic beverage sales data. There are Perivenular fibrosis and deposition of fibronectin occurs
conflicting data regarding a possible lower risk of liver in 40%-60% of patients who ingest more than 40-80
injury in wine drinkers.18,19 One epidemiologic study has g/daily for an average of 25 years. Perivenular sclerosis has
estimated that for every 1-liter increase in per capita alco-
hol consumption (independent of type of beverage), there
was a 14% increase in cirrhosis in men and 8% increase in
Table 2. Quantity of Alcohol in a Standard Drink
women.20 These data must be considered in the context of
Region Amount Range
the limitations of measuring alcohol use and defining al-
coholic liver disease. The scientific literature has also used USA 12 g 9.3–13.2 g
Canada 13.6 g 13.6 g
a variety of definitions of what constitutes a standard UK 9.5 g 8–10 g
drink (Table 2). Most studies depend on interviews with Europe 9.8 g 8.7–10.0 g
patients or their families to quantify drinking patterns, a Australia and New Zealand 9.2 g 6.0–11.0 g
Japan 23.5 g 21.2–28.0 g
method that is subject to a number of biases, which may
lead to invalid estimates of alcohol consumption.21 Adapted from Turner.263 To standardize, many authorities recommend conver-
Although there are limitations of the available data, the sion to grams of alcohol consumed. To convert concentrations of alcohol, usually
listed in volume percent (equivalent to the volume of solute/volume of solution
World Health Organization’s Global Alcohol database, 100), the percentage of alcohol by volume (% vol/vol) is multiplied by the specific
which has been in existence since 1996, has been used to gravity of alcohol, 0.79 g/mL.264
3. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 309
been identified as a significant and independent risk factor odds of developing cirrhosis or lesser degrees of liver dis-
for the progression of alcoholic liver injury to fibrosis or ease with a daily alcohol intake of 30 g/day were 13.7
cirrhosis.33,35 Progression of ALD culminates in the de- and 23.6, respectively, when compared with nondrink-
velopment of cirrhosis, which is usually micronodular, ers.50
but may occasionally be mixed micronodular and ma- The type of alcohol consumed may influence the risk
cronodular.36 of developing liver disease. In a survey of more than
A subset of patients with ALD will develop severe al- 30,000 persons in Denmark, drinking beer or spirits was
coholic hepatitis (AH), which has a substantially worse more likely to be associated with liver disease than drink-
short-term prognosis.37 AH also represents a spectrum of ing wine.18
disease, ranging from mild injury to severe, life-threaten- Another factor that has been identified is the pattern of
ing injury, and often presents acutely against a back- drinking. Drinking outside of meal times has been re-
ground of chronic liver disease.38,39 The true prevalence is ported to increase the risk of ALD by 2.7-fold compared
unknown, but histologic studies of patients with ALD to those who consumed alcohol only at mealtimes.52
suggest that AH may be present in as many as 10%-35% Binge drinking, defined by some researchers as five drinks
of hospitalized alcoholic patients.40-42 Typically, symp- for men and four drinks for women in one sitting, has also
tomatic patients present with advanced liver disease, with been shown to increase the risk of ALD and all-cause
concomitant cirrhosis in more than 50%, and superim- mortality.53,54
posed acute decompensation. Even patients with a rela- Women have been found to be twice as sensitive to
tively mild presentation, however, are at high risk of
alcohol-mediated hepatotoxicity and may develop more
progressive liver injury, with cirrhosis developing in up to
severe ALD at lower doses and with shorter duration of
50%.43,44 The likelihood that AH will progress to perma-
alcohol consumption than men.55 Several studies have
nent damage is increased among those who continue to
shown differing blood alcohol levels in women versus
abuse alcohol. Abstinence from alcohol in one small series
men after consumption of equal amounts of alcohol.56
did not guarantee complete recovery. Only 27% of ab-
This might be explained by differences in the relative
staining patients had histologic normalization, whereas
18% progressed to cirrhosis, and the remaining patients amount of gastric alcohol dehydrogenase, a higher pro-
had persistent AH when followed for up to 18 months.45 portion of body fat in women, or changes in alcohol ab-
sorption with the menstrual cycle.57 Based on
III. Risk Factors epidemiological evidence of a threshold effect of alcohol,
a suggested “safe” limit of alcohol intake had been 21
Unlike many other hepatotoxins, the likelihood of de-
units per week in men and 14 units per week in women
veloping progressive alcohol-induced liver disease or cir-
who have no other chronic liver disease58,59 (where a unit
rhosis is not completely dose-dependent, because it occurs
is defined as the equivalent of 8 g of ethanol). However,
in only a subset of patients. A number of risk factors have
other data suggest that a lower quantity may be toxic in
been identified that influence the risk of development and
progression of liver disease. women, implying a lower threshold of perhaps no more
The amount of alcohol ingested (independent of the than 7 units per week.47 A higher risk of liver injury may
form in which it is ingested) is the most important risk be associated with an individual’s racial and ethnic heri-
factor for the development of ALD.46 The relationship tage.60 The rates of alcoholic cirrhosis are higher in Afri-
between the quantity of alcohol ingested and the develop- can-American and Hispanic males compared to
ment of liver disease is not clearly linear.47,48 However, a Caucasian males and the mortality rates are highest in
significant correlation exists between per capita consump- Hispanic males.61 These differences do not appear to be
tion and the prevalence of cirrhosis.49 The risk of devel- related to differences in amounts of alcohol consumed.62
oping cirrhosis increases with the ingestion of 60-80 The presence and extent of protein calorie malnutri-
g/day of alcohol for 10 years or longer in men, and 20 tion play an important role in determining the outcome
g/day in women.6,50 Yet, even drinking at these levels, of patients with ALD. Mortality increases in direct pro-
only 6%-41% develop cirrhosis.6,51 In a population-based portion to the extent of malnutrition, approaching 80%
cohort study of almost 7000 subjects in two northern in patients with severe malnutrition (i.e., less than 50% of
Italian communities, even among patients with very high normal).63 Micronutrient abnormalities, such as hepatic
daily alcohol intake ( 120 g/day), only 13.5% developed vitamin A depletion or depressed vitamin E levels, may
ALD.50 The risk of cirrhosis or noncirrhotic chronic liver also potentially aggravate liver disease.64 Diets rich in
disease increased with a total lifetime alcohol intake of polyunsaturated fats promote alcohol-induced liver dis-
more than 100 kg, or a daily intake 30 g/day.50 The ease in animals,65 whereas diets high in saturated fats may
4. 310 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
be protective. Obesity and excess body weight have been evidence of alcohol abuse, such as questionnaires, infor-
associated with an increased risk of ALD.66,67 mation from family members, or laboratory tests to
In addition to environmental factors, genetic factors strengthen or confirm a clinical suspicion.86
predispose to both alcoholism and ALD.68-70 Children of
alcoholics raised in adopted families had a significantly A. Screening for Alcohol Abuse
higher rate of alcohol dependence than did adopted chil- Clinicians commonly fail to screen patients, and thus
dren of nonalcoholics, who served as controls (18% versus fail to recognize or treat alcoholism appropriately.87 The
5%).71 In population-based studies, monozygotic twins clinical history which may suggest alcohol abuse or alco-
were approximately twice as likely to drink as dizygotic hol dependence includes the pattern, type, and amount of
twins; among those who drank, monozygotic twins were alcohol ingested, as well as evidence of social or psycho-
more likely to have a similar frequency and quantity of logical consequences of alcohol abuse. These may be sug-
alcohol consumption.72 Moreover, monozyotic twins gested by other injuries or past trauma, such as frequent
have a significantly higher prevalence of alcoholic cirrho- falls, lacerations, burns, fractures, or emergency depart-
sis than do dizygotic twins.73 ment visits.88 Biochemical tests have been considered to
Finally, polymorphisms of genes involved in the me- be less sensitive than questionnaires in screening for alco-
tabolism of alcohol (including alcohol dehydrogenase, ac- hol abuse,89,90 but may be useful in identifying re-
etaldehyde dehydrogenase and the cytochrome P450 lapse.91,92 Various questionnaires have been used to detect
system), and in those which regulate endotoxin-mediated alcohol dependence or abuse, and include the CAGE, the
release of cytokines have been associated with ALD.74,75 MAST (Michigan Alcoholism Screening Test), and the
However, to date, specific genetic abnormalities for sus- Alcohol Use Disorders Identification Test (AUDIT).89,93
ceptibility to alcohol abuse and the development of ALD The use of a structured interview, using instruments such
have not yet been firmly established. as the Lifetime Drinking History, is often used as a gold
There is a clear synergistic relationship between standard for quantifying lifetime alcohol consumption.94
chronic viral hepatitis and alcohol, resulting in more ad- The CAGE questionnaire was originally developed to
vanced liver disease jointly than separately. The combina- identify hospitalized inpatients with alcohol problems,
tion of hepatitis C virus and alcohol predisposes to more and remains among the most widely used screening in-
advanced liver injury than alcohol alone,76,77 with disease struments. It has been faulted, however, on several mea-
at a younger age, more severe histological features, and a sures: it focuses on the consequences of alcohol
decreased survival.78 In a large cohort study of the effect of consumption rather than on the amount of actual drink-
heavy alcohol abuse in patients with posttransfusion hep- ing, and it refers to lifetime patterns of behavior, rather
atitis C, the risk of cirrhosis was elevated 30-fold.79 Al- than short-term or recent changes. Its virtues, however,
though the precise toxic threshold for alcohol is not include its ease of implementation: it is short (four ques-
known, and may be lower and nonuniform among pa- tions), simple (yes/no answers), and can be incorporated
tients at risk, it seems prudent in light of these data to into the clinical history or is self-administered as a written
advise patients with hepatitis C to abstain from even mod- document. As a result of its longevity, it has been tested in
erate quantities of alcohol. a wide range of populations.
One meta-analysis of its characteristics, using a cutoff
IV. Diagnosis of more than two positive responses, found an overall
The diagnosis of ALD is based on a combination of pooled sensitivity and specificity of 0.71 and 0.90, respec-
features, including a history of significant alcohol intake, tively.95 The CAGE questionnaire is familiar to most phy-
clinical evidence of liver disease, and supporting labora- sicians, and has been suggested for use in general
tory abnormalities.80 Unfortunately, the ability to detect screening96 (Table 3). The AUDIT is a 10-item question-
these is constrained by patient and physician factors, as naire developed by the World Health Organization to
well as diagnostic laboratory shortcomings. Denial of al-
cohol abuse and underreporting of alcohol intake are
common in these patients.81,82 Physicians underestimate Table 3. The CAGE Questionnaire265
alcohol-related problems and make specific recommenda- 1. Have you ever felt you should cut down on your drinking?
2. Have people annoyed you by criticizing your drinking?
tions even less frequently.83,84 Both the physical findings 3. Have you ever felt bad or guilty about your drinking?
and laboratory evidence for ALD may be nondiagnostic, 4. Have you ever had a drink first thing in the morning to steady your nerves
especially in patients with mild ALD or early cirrhosis.85 or to get rid of a hangover (eye-opener)?
Therefore, the clinician must have a low threshold to raise Scoring: Each response is scored as 0 or 1, with a higher score indicative of
the issue of possible ALD, and has to rely on indirect alcohol-related problems, and a total of 2 or more clinically significant.
5. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 311
Table 4. AUDIT Questionnaire102
Questions 0 1 2 3 4
1. How often do you have a drink Never Monthly or less 2 to 4 times 2 to 3 times 4 or more times
containing alcohol? a month a week a week
2. How many drinks containing 1 or 2 3 or 4 5 or 6 7 to 9 10 or more
alcohol do you have on a typical
day when you are drinking?
3. How often doyou have 5 or more Never Less than monthly Monthly Weekly Daily or almost
drinks on one occasion? daily
4. How often during the last year have Never Less than monthly Monthly Weekly Daily or almost
you found that you were not able daily
to stop drinking once you had
started?
5. How often during the last year have Never Less than monthly Monthly Weekly Daily or almost
you failed to do what was normally daily
expected of you because of
drinking?
6. How often during the last year have Never Less than monthly Monthly Weekly Daily or almost
you needed a first drink in the daily
morning to get yourself going after
a heavy drinking session?
7. how often during the last year have Never Less than monthly Monthly Weekly Daily or almost
you had a feeling of guilt or daily
remorse after drinking?
8. How often during the last year have Never Less than monthly Monthly Weekly Daily or almost
you been unable to remember what daily
happened the night before because
of your drinking?
9. Have you or someone else been No Yes, but not in Yes, during the
injured because of your drinking? the last year last year
10. Has a relative, friend, doctor or No Yes, but not in Yes, during the
other health care worker been the last year last year
concerned about your drinking or
suggested you cut down?
To score the AUDIT questionnaire, sum the scores for each of the 10 questions. A total 8 for men up to age 60, or 4 for women, adolescents, or men over
age 60 is considered a positive screening test.
avoid ethnic and cultural bias97 and focuses on the iden- Regardless of which screening instrument is selected,
tification of heavy drinkers. It has a higher sensitivity and however, it is important for clinicians to incorporate
specificity than shorter screening instruments (with sen- screening into their general practice.98,103 This may be
sitivity ranging from 51%-97%, and specificity of 78%- especially important, because some data suggest that these
96% in primary care).98 It has been suggested that it has screening instruments may improve the ability of physi-
three advantages over other screening tests: it may identify cians to predict long-term clinical outcomes, including
drinkers at risk who are not yet alcohol-dependent; it hospitalization for alcohol-related diagnoses.104
includes a measure of consumption; and lastly, it includes A biomarker in longstanding use, gamma glutamyl
both current and lifetime drinking time spans. It is more transpeptidase (GGT), has been evaluated in a number of
likely to detect problem drinking before overt alcohol settings, including large population surveys.105,106 Unfor-
dependence or abuse might be diagnosed, and thus may tunately, low sensitivity and specificity limit the useful-
be more robust and effective across a variety of popula- ness of elevated GGT to diagnose alcohol abuse,107-109 the
tions.99-101 One possible algorithm for clinicians suggests levels of which may fluctuate with extensive liver inju-
asking about quantity of alcohol consumed, and number ry.110 Lower levels of GGT ( 100) or a total bilirubin/
of heavy drinking days in the preceding year (i.e., 5 GGT ratio 1 have been described as a predictor of
drinks/day for men or 4 drinks/day for women), as well 1-year mortality in patients with alcoholic cirrhosis,110
as a version of the AUDIT questionnaire102 (Table 4). An although this has not consistently added prognostic abil-
AUDIT score of 8, or having had one or more heavy ity to other laboratory tests.111 In combination with other
drinking days constitutes a positive screening test, and biomarkers, however, GGT may add independent infor-
should prompt further evaluation to rule out an alcohol mation in diagnosing alcohol abuse or problem drink-
use disorder.102 ing.112 Macrocytosis is seen in individuals abusing alcohol
6. 312 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
but this condition lacks sensitivity. A combination of the physical findings are more commonly observed in
raised GGT and mean corpuscular volume or changes in ALD (parotid enlargement, Dupuytren’s contracture,
these values over time in hospitalized patients may im- and especially those signs associated with feminization)
prove the sensitivity for diagnosing alcohol abuse. Multi- than in non-ALD, no single physical finding or constel-
ple other candidate biomarkers that may detect alcohol lation of findings is 100% specific or sensitive for ALD.130
use or abuse objectively have been studied.113,114 Carbo- Some of the physical exam features may also carry some
hydrate-deficient transferrin has been the best studied, independent prognostic information, with the presence
but has limited sensitivity and specificity.115 Its test char- of specific features associated with an increased risk of
acteristics are also influenced by a number of other factors, mortality over 1 year. These include (with their associated
including age, sex, body mass index, and other chronic relative risks): hepatic encephalopathy (4.0), presence of
liver diseases.116-118 Despite enthusiasm about a possible visible veins across the anterior abdominal wall (2.2),
quantitative, reliable assay of alcohol consumption or edema (2.9), ascites (4.0), spider nevi (3.3), and weakness
abuse, the lack of sensitivity and specificity prevent reli- (2.1).131 Although this is somewhat helpful clinically,
ance on any single biomarker.119 findings from the physical exam must be interpreted with
caution, because there is considerable heterogeneity in the
B. Diagnosis of ALD assessment of each of these features when different exam-
The diagnosis of ALD is made by documentation of iners are involved.132 Several authors have reported the
alcohol excess and evidence of liver disease.120 No single detection of an hepatic bruit in the setting of AH.133 This
laboratory marker definitively establishes alcohol to be the has been used in some centers as a diagnostic criterion for
etiology of liver disease. Furthermore, alcohol may be one AH.134 However, the sensitivity, as well as the specificity
of a number of factors causing liver injury, and the specific of this finding is uncertain.135 In one series of 280 con-
contributory role of alcohol alone may be difficult to as- secutive hospitalized patients, only 4 of 240 (or 1.7%)
sess in a patient with multifactorial liver disease. A num- with AH and cirrhosis had an audible bruit.136 Caution
ber of laboratory abnormalities, including elevated serum about adopting this as a diagnostic criterion has therefore
aminotransferases, have been reported in patients with been advised.137
alcoholic liver injury, and used to diagnose ALD.121 Se- It is important for physicians caring for these patients
rum aspartate aminotransferase (AST) is typically elevated to recognize that ALD does not exist in isolation, and that
to a level of 2-6 times the upper limits of normal in severe other organ dysfunction related to alcohol abuse may co-
alcoholic hepatitis. Levels of AST more than 500 IU/L or an exist with ALD, including cardiomyopathy,138,139 skeletal
alanine aminotransferase (ALT) 200 IU/L are uncom- muscle wasting,140 pancreatic dysfunction, and alcoholic
monly seen with alcoholic hepatitis (other than alcoholic neurotoxicity.141 Evidence of these must be sought during
foamy degeneration, or concomitant acetaminophen over- the clinical examination, so that appropriate treatment
dose),122 and should suggest another etiology. In about 70% may be provided.142
of patients, the AST/ALT ratio is higher than 2, but this may
be of greater value in patients without cirrhosis.123-125 Ratios D. Hepatic Imaging
greater than 3 are highly suggestive of ALD.126 Imaging studies have been used to diagnose the pres-
ence of liver disease but do not have a role in establishing
C. Physical Examination alcohol as the specific etiology of liver disease. However,
Physical exam findings in patients with ALD may the diagnosis of fatty change, established cirrhosis and
range from normal to those suggestive of advanced cirrho- hepatocellular carcinoma may be suggested by ultra-
sis. As in other forms of chronic liver disease, physical sound, computed tomography scan, or magnetic reso-
exam features generally have low sensitivity, even for the nance imaging (MRI) and confirmed by other laboratory
detection of advanced disease or cirrhosis, although they investigations.143,144 The major value of imaging studies is
may have higher specificity.127 It has been suggested, to exclude other causes of abnormal liver tests in a patient
therefore, that the presence of these features may have who abuses alcohol, such as obstructive biliary pathology,
some benefit in “ruling in” the presence of advanced dis- or infiltrative and neoplastic diseases of the liver.145 MRI
ease.127 Features specific for ALD are perhaps even more has been used as an adjunct to diagnose cirrhosis, and to
difficult to identify. Palpation of the liver may be normal distinguish end-stage liver disease related to viral hepatitis
in the presence of ALD, and does not provide accurate infection from ALD. Specific features that may be sugges-
information regarding liver volume.128 Certain physical tive of alcoholic cirrhosis include a higher volume index of
exam findings have been associated with a higher likeli- the caudate lobe, more frequent visualization of the right
hood of cirrhosis among alcoholics.129 Although some of posterior hepatic notch, and smaller size of regenerative
7. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 313
nodules of the liver in patients with cirrhosis on the basis sicians’ clinical impression may correlate only moderately
of ALD versus chronic viral hepatitis.146 Although well with the histologic findings on liver biopsy. Studies
changes were identified on ultrasound and MRI, it is un- that have included a liver biopsy in all patients with pre-
clear whether these results are generalizable.146,147 sumed AH have shown histologic confirmation in only
70%-80% of patients.156 The incentive to make a defin-
E. Liver Biopsy in ALD itive histologic diagnosis, however, is partly dependent on
Although not essential in the management of ALD, a the possible risks of a biopsy, as well as the risks involved
liver biopsy is useful in establishing the diagnosis.144 As with particular treatments. If no treatment for ALD or
many as 20% of patients with a history of alcohol abuse AH is contemplated, based on noninvasive estimates of an
have a secondary or coexisting etiology for liver disease.148 individual patient’s prognosis, it usually is not necessary
In the absence of decompensated disease, clinical and bio- to make a histologic diagnosis. Alternatively, if an inves-
chemical indicators are poor markers of the severity of tigational treatment or a therapy with associated risk is
liver disease, and a biopsy is useful in establishing the stage contemplated, the risk-benefit ratio involved in pursuing
and severity of liver disease.144,149 a liver biopsy may change.
The histological features of alcohol-induced hepatic Recommendation:
injury vary, depending on the extent and stage of injury. 1. Clinicians should discuss alcohol use with pa-
These may include steatosis (fatty change), lobular in- tients, and any suspicion of possible abuse or excess
flammation, periportal fibrosis, Mallory bodies, nuclear should prompt use of a structured questionnaire and
vacuolation, bile ductal proliferation, and fibrosis or cir- further evaluation (Class I, level C).
rhosis.24 These may coexist in the same biopsy, however, 2. For patients with a history of alcohol abuse or
and are not individually pathognomonic of ALD. The excess and evidence of liver disease, further laboratory
clinical diagnosis of AH is made based on a typical pre- tests should be done to exclude other etiologies and to
sentation, with severe liver dysfunction in the context of confirm the diagnosis (Class I, level C).
excessive alcohol consumption, and the exclusion of other 3. Patients with ALD and suggestive symptoms
causes of acute and chronic liver disease. In the subset of should be screened for evidence of other end-organ
patients with AH, a liver biopsy may demonstrate specific damage, as appropriate (Class I, level C).
histologic features, including confluent parenchymal ne- 4. For patients with a clinical diagnosis of severe
crosis, steatosis, deposition of intrasinusoidal and pericen- AH for whom medical treatment is contemplated, or
tral collagen, ballooning degeneration, and lobular for those in whom reasonable uncertainty exists re-
inflammation affecting the perivenular regions in the ear- garding the underlying diagnosis, a liver biopsy should
liest stages.34 The liver may be infiltrated with polymor- be considered. This decision will depend on local
phonuclear cells, typically clustered around cytoplasmic expertise and ability in performing a liver biopsy in
structures known as Mallory bodies,150 which represent patients with coagulopathy, the patient’s severity of
aggregated cytokeratin intermediate filaments and other illness, and the type of therapy under consideration
proteins. In addition to confirming the diagnosis and (Class I, level C).
staging the extent of disease, specific features on liver bi-
opsy also convey prognostic importance. The severity of V. Prognostic Factors
inflammation (i.e., degree of polymorphonuclear cell in- A. Prognosis in Alcoholic Hepatitis
filtration) and cholestatic changes correlate with increas- Decisions regarding treatment are critically dependent
ingly poor prognosis, and may also predict response to on the ability to estimate a given patient’s prognosis.
corticosteroid treatment in severe AH.151,152 Megamito- Many individual clinical and laboratory features, along
chondria in alcoholic hepatitis may be associated with a with specific histologic features have also been tested as
milder form of AH, a lower incidence of cirrhosis and measures of disease prognosis. In AH, the Maddrey dis-
fewer complications with a good long-term survival.153 criminant function (MDF), a disease-specific prognostic
AH is associated with perivenular and pericellular fibrosis score, has been used to stratify a patient’s severity of ill-
which may be a harbinger of future cirrhosis, especially in ness.157 The initial formula was derived in the context of
patients who continue to abuse alcohol or those who are clinical trials of alcoholic hepatitis, and later modified to:
coinfected with hepatitis C virus.33,154 Mallory bodies, MDF 4.6 (Patient’s prothrombin time control pro-
giant mitochondria, neutrophilic infiltration, and fibrosis thrombin time) total bilirubin (mg/dL).158 Patients
may be seen in conditions other than ALD.155 with a score of greater than or equal to 32 were at the
Although a liver biopsy may not be practical in the highest risk of dying, with a one month mortality as high
management of all patients, it has been shown that phy- as 30%-50%.151 In particular, those with evidence of both
8. 314 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
Table 5. Prognostic Scoring Systems Used for Patients with Alcoholic Hepatitis
Derivation
Name Set Elements Test Characteristics
1. Maddrey (modified) n 66 MDF 4.6 (Patient’s PT control PT) total bilirubin (mg/dL). Poor prognosis if score 32
Discriminant Function
(1989)158
2. MELD score (2001)†160 n 1179 MELD Score 3.8 * loge(bilirubin in mg/dL) 11.2 * loge(INR) Poor prognosis if 18
9.6 * loge(creatinine mg/dL) 6.4
3. Glasgow Alcoholic Hepatitis n 241 Score*: Poor prognosis if score 8 (for
score (2005)161 1 2 3 score calculated on hospital
Age 50 50 – day 1 or day 7)
WCC 15 15 –
Urea (mmol/L) 5 5 –
PT ratio 1.5 1.5–2.0 2
Bilirubin (mg/dL) 7.3 7.3–14.6 14.6
*The GAH score is calculated by summing the points assigned for each of the 5 variables: age, white blood cell count, blood urea nitrogen, PT as a ratio of the patient
to the control, and the bilirubin. This is done on hospital day 1 or on day 7.
†The MELD score has also been used to estimate 90-day mortality166; an online calculator is available: www.mayoclinic.org/meld/mayomodel7.html.
hepatic encephalopathy and an elevated MDF were at Several studies have also demonstrated the utility of
highest risk. Although relatively easy to use, and based on repeat testing and calculation of these indices during the
standard laboratory tests, several drawbacks to the use of course of hospitalization, including MELD or MDF score
the MDF have been noted. Although it is a continuous at one week, and degree of change. A change of 2 points
measure, its interpretation (using a threshold of 32) has in the MELD score in the first week has been shown to
converted it into an essentially categorical method of clas- independently predict in-hospital mortality.164 The
sification. Once patients have exceeded that threshold, GAHS was recently derived, and its test characteristics
their risk for dying is higher, but not specified. Dynamic compared to the MDF and the MELD scores. Although it
models, which incorporate the changes in laboratory had an overall higher accuracy, it was substantially less
studies over time, have also been used to estimate the sensitive for predicting one month and three month mor-
outcome in patients, including the change in bilirubin in tality compared to either the MDF or the MELD.161 The
the first week of hospitalization, which is significantly degree of portal hypertension may be a sensitive marker
associated with outcome of patients with alcoholic hepa- for the severity of liver injury.167 A recently proposed
titis treated with prednisolone.159 scoring system combines measurements of a marker of
Table 5 outlines some of the prognostic scoring sys-
portal hypertension, asymmetric dimethylarginine and its
tems used for patients with alcoholic hepatitis.
stereoisomer, to predict outcomes.168 This combined
Other scoring systems have also been proposed to strat-
score has been compared to the CTP score, MELD, and
ify patients, including the combined clinical and labora-
MDF, and shown to have an overall sensitivity of 73%
tory index of the University of Toronto,131 the Beclere
and specificity of 83%, which was at least as good as other
model,151 the MELD (Model for End-Stage Liver Dis-
ease) score,160 and the Glasgow Alcoholic Hepatitis Score scoring systems.168 These results, however, require further
(GAHS).161 The diagnostic abilities of the latter two validation.
models have been tested against the MDF and other scor- As the goal of early detection of patients at highest risk
ing systems for cirrhosis (such as the Child-Turcotte- of poor outcome requires maximization of the sensitivity
Pugh score, or CTP) in terms of specific test of the test score, it would seem reasonable to use the MDF
characteristics, including sensitivity and specificity, at (with a cutoff of 32, and/or the presence of encephalopa-
least in some populations.162,163 Because of the inherent thy) to select patients for therapy.
trade-offs involved in setting test thresholds, optimal cut Recommendation:
points are not clearly established for each of these indices. 5. Patients presenting with a high clinical suspicion
Some investigators have suggested specific cutoffs for of alcoholic hepatitis should have their risk for poor
these indices, including an MDF 32 or a MELD outcome stratified using the Maddrey Discriminant
score 11, that appear to be roughly equivalent in ability Function, as well as other available clinical data.
to detect patients with a poor prognosis, with similar sen- Evaluating a patient’s condition over time with serial
sitivity and specificity.162 Others have suggested higher calculation of the MELD score is also justified (Class
MELD cutoffs of 18,164 19,165 or 21166 (Table 6). I, level B).
9. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 315
Table 6. Comparisons of Diagnostic Indices
Author Patient Population Outcome AUROC
Sheth 162 N 34 patients with alcoholic hepatitis MELD 11: MELD: 0.82
hospitalized 1997-2000. 21% 30 day mortality Sensitivity 86% MDF: 0.86
Specificity: 81%
MDF 32:
Sensitivity 86%
Specificity 48%
Srikureja164 N 202 AH patients admitted 1997-2002. 29 Admission MELD 18: Admission MELD: 0.89
inpatient deaths Sensitivity 85% Admission CTP: 0.87
Specificity 84% Admission DF: 0.81
Admission MDF 32:
Sensitivity 83%
Specificity 60%
Admission CTP 12:
Sensitivity 76%
Specificity 80%
Dunn166 N 73 AH patients admitted 1995-2001. 16 Admission MELD 21: Admission MELD: 0.83
deaths in 90 days. Outcome: 30 day mortality Sensitivity 75% Admission MDF: 0.74
Specificity 75%
MDF 41:
Sensitivity 75%
Specificity 69
Soultati165 N 34 patients admitted 2000-2005; 2 MELD 30.5: MELD: 0.969
deaths/30 days, 5 deaths/90 days. Outcome: Sensitivity 1 MDF: 0.984
30 day mortality Specificity 0.937
MDF 108.68:
Sensitivity 1
Specificity 0.969
AUROC: area under the ROC curve, with optimal test results closest to 1
VI. Therapy the time course of follow-up and the definition of recidi-
vism (e.g., any alcohol consumption versus moderate to
Therapy of ALD is based on the stage of the disease and
harmful drinking), but over the course of 1 year, relapse
the specific goals of treatment.169,170 Complications of
rates range from 67%-81%.181 Therefore, several medica-
cirrhosis, including evidence of hepatic failure (encepha-
tions have been tried to help sustain abstinence. One of
lopathy) as well as portal hypertension (ascites, variceal
the first agents to be used, disulfiram, was approved by the
bleeding), are treated as in patients with non-ALD, with
U.S. Food and Drug Administration in 1983. However, a
additional attention given to other organ dysfunction as-
review of the published literature concluded that there
sociated specifically with alcohol.170
was little evidence that disulfiram enhances abstinence,182
A. Abstinence and based on its poor tolerability, its use has been largely
Abstinence is the most important therapeutic interven- supplanted by newer agents. Naltrexone, which was ap-
tion for patients with ALD.171 Abstinence has been shown proved in 1995 for the treatment of alcoholism, is a pure
to improve the outcome and histological features of he- opioid antagonist and controls the craving for alcohol.
patic injury, to reduce portal pressure and decrease pro- However, it also has been shown to cause hepatocellular
gression to cirrhosis, and to improve survival at all stages injury. A Cochrane systematic review of the use of nal-
in patients with ALD.171-174 However, this may be less trexone and nalmefene (another opioid antagonist) in 29
likely to occur in female patients.172,175,176 This improve- randomized clinical trials concluded that short-term
ment can be relatively rapid, and in 66% of patients ab- treatment with naltrexone lowers the risk of relapse.183
staining from alcohol, significant improvement was Acamprosate (acetylhomotaurine) is a novel drug with
observed in 3 months.177 Continued alcohol ingestion structural similarities to the inhibitory neurotransmitter
results in an increased risk of portal hypertensive bleeding, gamma amino butyric acid (GABA), and is associated
especially in patients who have previously bled, and wors- with a reduction in withdrawal symptoms.184 In 15 con-
ens both short-term and long-term survival.178 trolled trials, acamprosate has been shown to reduce with-
Recidivism is a major risk in all patients at any time drawal symptoms, including alcohol craving, but its
following abstinence.179,180 Estimates vary, depending on effects on survival are not yet known.185 Its effect is more
10. 316 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
pronounced in maintaining rather than inducing remis- alone. For those with more severe disease and therefore a
sion when used in combination with counseling and sup- more dismal prognosis, however, medical treatment
port. In detoxified alcoholics, it has been shown to should be considered.
decrease the rate of relapse, maintain abstinence, and de- 1. Nutrition Therapy. The presence of significant
crease severity of relapse when it occurs. It has not been protein calorie malnutrition is a common finding in alco-
shown to have a significant impact on alcoholics who have holics, as are deficiencies in a number of vitamins and
not been detoxified or become abstinent. Whether it has trace minerals, including vitamin A, vitamin D, thiamine,
any additional effect in combination with naltrexone is folate, pyridoxine, and zinc.193 In a Veterans Administra-
controversial. A recent large randomized controlled clin- tion Cooperative study of 363 patients with alcoholic
ical trial did not suggest substantial benefit of acamprosate hepatitis, 100% of patients were found to have protein
compared to naltrexone or to intensive counseling in and/or combined protein calorie malnutrition, based on
maintaining abstinence.186 There is a paucity of data anthropometric and laboratory testing.194 Moreover, the
about the use of these interventions in patients with ad- severity of malnutrition correlated with disease severity
vanced liver disease. One randomized clinical trial in pa- and outcomes.194
tients with cirrhosis suggested benefit in achieving and This early finding was the motivation for a number of
maintaining abstinence with the use of baclofen, a -ami- clinical trials of anabolic steroids, nutritional supplemen-
nobutyric acid B receptor agonist.187 tation, or aggressive enteral feeding. Several of these stud-
Recommendations: ies showed improvement in biochemical markers of liver
6. In patients with evidence of alcohol-induced function or nutritional parameters, but were unable to
liver disease, strict abstinence must be recommended, demonstrate an improvement in short-term survival.195
because continued alcohol use is associated with dis- At least in some trials, however, subgroups of patients
ease progression (Class I, level B). who achieved nutritional goals and positive nitrogen bal-
7. Naltrexone or acamprosate may be considered in ance had improved survival compared to those who did
combination with counseling to decrease the likelihood of not.196 As an example, in one study the mortality rate was
relapse in patients with alcohol abuse/dependence in 3.3% in the 30 patients in whom positive nitrogen bal-
those who achieve abstinence (Class I, level A). ance was achieved, but 58% in patients who remained in
negative nitrogen balance.196
B. Therapy for Alcoholic Hepatitis A recent study of nutritional therapy compared the
The cornerstone of therapy of alcoholic hepatitis is outcomes of 35 patients randomized to 1 month of en-
abstinence, although even patients who become abstinent teral tube feeding of 2000 kcal/day versus 40 mg of pred-
remain at increased risk of developing cirrhosis. However, nisone/day.197 No difference in mortality was noted, but
the risk of cirrhosis is clearly higher in those who continue the time course of deaths was different, with the patients
to drink,188,189 particularly among women.175,190 Al- randomized to enteral feeding dying at a median of 7 days,
though there are no clear dose– effect data, a threshold versus 23 days in the steroid treated group. Patients
exists for the development of alcoholic hepatitis, with risk treated with nutritional support who survived past the
increasing with consumption beyond 40 g of alcohol per first month seemed to have a decreased mortality com-
day.46,191 Furthermore, after an episode of AH, there is no pared to the steroid-treated patients (8% versus 37%).197
safe amount of alcohol consumption which can be recom- Although technically a negative study, the similar overall
mended, as alcoholic hepatitis can persist or redevelop. mortality rate in the treatment groups suggests a role for
There is a significant risk of recidivism in patients who nutritional intervention,198 particularly in light of the rel-
attempt to cut back but not stop drinking altogether.192 atively benign risk:benefit ratio. Based on these data,
Complete abstinence is therefore a reasonable lifetime other societies have recommended oral or parenteral sup-
recommendation. plements for patients with AH at risk of undernutri-
The need to consider therapy is less urgent in patients tion.199
with alcoholic hepatitis who have a low risk of complica- 2. Steroids. The most extensively studied interven-
tions as defined by an MDF score of 32, without he- tion in alcoholic hepatitis is the use of steroids, based on
patic encephalopathy, or a low MELD score (e.g., MELD 13 clinical trials that date back almost 40 years (Table 7).
18), or GAHS score of 8. This is particularly true in Most of these trials were small, and therefore had only
those whose liver score improves during hospitalization, limited statistical power to detect even moderate treat-
with a decrease in total bilirubin, as they will likely im- ment effects; five suggested an improvement in outcome,
prove spontaneously with abstinence and supportive care with decreased short term mortality in steroid-treated pa-
11. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 317
Table 7. Clinical Trials of Steroids in Patients with Alcoholic Hepatitis.
No. of Deaths: Deaths:
Author Date Patients Intervention placebo steroid
Porter266 1971 20 Prednisolone: 40 mg IV 10 days, then tapered: 4 7/9 6/11
mg/day 1 week, 2 mg/day 11 days, then 2
mg every 3rd day 15 days
Helman267 1971 37 Prednisolone: 40 mg/day 4 weeks, then tapered 6/17 1/20
over 2 weeks
Campra268 1973 45 Prednisone: 0.5 mg.kg 3 weeks, then 0.25 mg/kg 9/25 7/29
3 weeks
Blitzer269 1977 33 Prednisolone:40 mg/day 14 days, then 20 mg/day 5/16 6/12
4 days; 10 mg/day 4 day; 5 mg/day 4
days
Lesesne270 1978 14 Prednisolone: 40 mg/day 30 days, then tapered 7/7 2/7
over 2 weeks
Shumaker271 1978 27 Prednisolone: 80 mg/day 4-7 days, then tapered 7/15 6/12
off over 4 weeks
Maddrey157 1978 55 Prednisolone: 40 mg/day 30 days 6/31 1/24
Depew272 1980 28 Prednisolone: 40 mg/day 28 days, then tapered 7/13 8/15
over 14 days
Theodossi273 1982 55 Prednisolone: 1 g 3 days 16/28 17/27
Mendenhall274 1984 178 Prednisolone: 60 mg 4 days; 40 mg/day 4 days; 50/88 55/90
30 mg/day 4 days; 20 mg/day 4 days; 10
mg/day 7 days; 5 mg/day 7 days
Bories275 1987 45 Prednisolone: 40 mg/day 30 days 2/21 1/24
Carithers158 1989 66 Prednisolone: 32 mg/day 28 days, then 16 mg/day 11/31 2/35
7 days, then 8 mg/day 7 days
Ramond276 1992 61 Prednisolone: 40 mg/day 28 days 16/29 4/32
tients compared to placebo-treated patients, whereas trials in patients with comparable measures of disease se-
eight showed no effect. It is important to note, however, verity (i.e., an MDF 32). The result showed a signifi-
that these trials used varying inclusion and exclusion cri- cant increase in short-term survival among treated
teria, dosing, and were done in a variety of patient popu- patients compared to control patients: 84.6% versus
lations. Three meta-analyses have analyzed data from 65%.207 This represents a modest absolute reduction in
these trials and showed an improvement in survival in risk, but a 30% relative risk reduction, and translates into
treated patients200-202; one meta-regression, however, us- a number needed to treat of 5, i.e., five patients need to be
ing different statistical weighting of the varying trials, was treated to avert one death. This last meta-analysis also
unable to show any difference.203 The most recent meta- excluded a recent trial comparing steroids to a combina-
analysis of these data did not show a statistically signifi- tion of antioxidants, which showed a similar protective
cant effect of steroids on mortality among all patients effect of corticosteroids among treated patients.208 Al-
treated, although it did demonstrate an effect of steroids though it is possible that antioxidants themselves may be
in the subgroup of patients with hepatic encephalopathy detrimental,209 the doses used seem unlikely to account
and/or a MDF score 32.204 The presence of substantial for the differences in survival, and the consistency of the
statistical heterogeneity in this subgroup of studies pre- data suggest a protective effect of steroids.
vented the authors from reporting an overall beneficial Although the doses and durations of steroid treatment
effect. The implication of this finding is unclear, as statis- used in the clinical trials were variable, the best available
tical heterogeneity among subgroups is a function of both evidence suggests a dose of prednisolone (40 mg/day for 4
clinical differences and/or methodologic differences weeks then tapered over 2-4 weeks, or stopped, depending
among studies, and these analyses may be reflect bias or on the clinical situation) should be used in favor of pred-
confounding.205 One potential approach to resolve this is nisone.210 It is important to recognize that the efficacy of
the use of individual patient data across clinical trials, steroids has not been evaluated in patients with severe
which represents the “gold standard” approach to meta- alcoholic hepatitis and concomitant pancreatitis, gastro-
analysis.206 Although it is impractical to retrieve and com- intestinal bleeding, renal failure, or active infection,
bine primary data from all the clinical trials in this field, which were exclusion criteria in many of the early studies
where large variation in studies over time exists, this ap- of alcoholic hepatitis.
proach was pursued with the use of a combined dataset, An important issue in all studies of medical therapy,
using pooled primary data from three placebo controlled and one that has been recognized for some time in this
12. 318 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
literature, is the possibility that these therapies may not be substantial decreases in other prognostic markers, includ-
effective at an advanced stage of disease. Just as there is a ing cytokine levels and MDF scores were seen in patients
threshold for the use of steroids (i.e., identifying patients treated with combination therapy. Another trial, per-
at high risk of mortality defined by a MDF score 32 ), formed at 19 centers in France, randomized 36 patients
there may also be a ceiling beyond which medical thera- with biopsy proven alcoholic hepatitis and an MDF 32
pies aimed at decreasing the inflammatory cascade may to prednisolone (40 mg/day for 4 weeks), versus pred-
cause more harm than benefit. One study examined this nisolone along with infliximab (10 mg/kg, given at study
issue, and suggested that patients with a MDF 54 were entry, and again at 2 weeks and 4 weeks after entry).216
at a higher mortality risk from use of steroids than from The trial was stopped prematurely after seven deaths had
not being treated.211 This cutoff, however, needs to be occurred in the infliximab group, compared with three in
confirmed. the prednisolone arm. Four of the seven deaths in the
One recently derived model used six variables to pre- infliximab arm were related to infectious etiologies, com-
dict 6-month mortality in patients who were universally pared to one in the prednisolone group. The design, and
treated with steroids (including age, renal insufficiency in particular, the dose of infliximab chosen in the study,
(serum creatinine 1.3 or creatinine clearance 40), has been criticized as predisposing to these infections.217
albumin, prothrombin time, bilirubin, and change in bil- The utility of etanercept (given six times over 3 weeks)
irubin over 1 week), and showed an improved prognostic was tested in 48 patients with moderate to severe alcoholic
ability compared to MDF or GAHS scores.212 This hepatitis (MELD score 15); unfortunately, no signifi-
model, available on the internet (www.lillemodel.com) cant difference in 1-month mortality was seen in the
may allow identification of patients who remain at high treated patients compared to patients given placebo, and
risk to be treated with other interventions. an increased mortality was seen at 6 months.218
3. Anticytokine Therapy. A wealth of evidence sug- Although a strong rationale remains for the use of anti-
gests that dysregulated cytokines, including tumor necro- TNF therapy in alcoholic hepatitis, there is also a theoret-
sis factor alpha (TNF ) and a host of downstream ical basis for minimizing TNF inhibition, because it plays
cytokines play a pivotal role in the pathophysiology of a role in liver regeneration as well as apoptosis.219 Thus, in
AH. Thus, several agents have been studied that impact light of the poor clinical outcomes observed in the largest
the immunologic milieu, targeting specific cytokines, and of the infliximab trials and the etanercept study, the use of
TNF in particular. these parenteral TNF inhibitors should be confined to
Among the first agents to be studied was pentoxifyl- clinical trials, and recommendations regarding specific
line, an oral phosphodiesterase inhibitor which also in- therapy will need to await the results of these trials. There
hibits the production of TNF , among other cytokines. A are no substantive clinical data comparing the use of ste-
randomized placebo controlled clinical trial tested pen- roids or nutrition to specific anti-TNF therapies.
toxifylline in 101 patients with clinical evidence of severe 4. Combination Therapy. Although it is assumed
AH.213 The in-hospital mortality in the treated patients that each of these different treatments may operate via
was 40% lower than in the placebo arm, with the bulk of independent mechanisms, there are only minimal data
the reduction related to a substantially lower likelihood of regarding the comparative benefit of sequential therapies
developing hepatorenal syndrome (HRS). HRS was re- or combined approaches. One study tested the use of
sponsible for 50% of the 12 deaths in the treatment arm, pentoxifylline in 29 patients with severe AH (MDF 32)
compared to 91.7% of the 24 deaths in the placebo group. who did not respond to steroids based on a drop in bili-
Other specific inhibitors of TNF that have been stud- rubin level after 1 week of prednisolone treatment. Com-
ied include infliximab, a monoclonal chimeric anti-TNF pared to previously treated patients (who were continued
antibody, and etanercept, a fusion protein containing the on steroids despite lack of bilirubin response), there was
ligand-binding portion of the human TNF receptor fused no improvement in 2-month survival, thus arguing
to the Fc portion of human immunoglobulin G1.214 In against a two-step strategy with an early switch to pentoxi-
the first clinical trial of infliximab, 20 patients with biopsy fylline.220 Several older studies had examined the role of
proven alcoholic hepatitis and an MDF score between 32 anabolic steroids with nutritional interventions (based on
and 55 (based on the original Maddrey score, which dem- the presumption that both interventions acted via a sim-
onstrated an increased mortality at a score 93) were ilar mechanism, i.e., correction of protein calorie malnu-
randomized to either 5 mg/kg of infliximab plus 40 mg/ trition).221 One pilot study evaluated the role of steroids
day of prednisone (n 11) or to prednisone alone.215 No in combination with enteral nutrition in 13 patients with
substantial difference in overall mortality was found, but severe AH, and found an overall mortality of 15%—pos-
13. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 319
Fig. 1. Proposed algorithm for alcoholic hepatitis.
sibly an improvement from expected.222 With the advent A proposed treatment algorithm for alcoholic hepatitis
of new therapies, it is necessary to reconsider the risk- is shown in Fig. 1.
benefit ratio of medical treatment. It has been suggested Recommendations:
that it may be possible to use less toxic therapies at a lower 8. All patients with alcoholic hepatitis should be
threshold of disease severity.223 However, the exact role of counseled to completely abstain from alcohol (Class I,
these new therapies, and the threshold for their use, is still level B).
undefined. 9. All patients with alcoholic hepatitis or advanced
5. Other Treatments. Many other therapeutic inter- ALD should be assessed for nutritional deficiencies
ventions have been studied in alcoholic hepatitis, but have (protein-calorie malnutrition), as well as vitamin and
not been able to show convincing benefit, including trials mineral deficiencies. Those with severe disease should
of antioxidants (vitamin E, silymarin, combination anti- be treated aggressively with enteral nutritional ther-
oxidants), antifibrotics (colchicine), antithyroid drugs apy (Class I, level B).
(propylthiouracil [PTU]), promoters of hepatic regener- 10. Patients with mild-moderate alcoholic hepati-
ation (insulin and glucagons), anabolic steroids (oxan-
tis— defined as a Maddrey score of <32, without
drolone and testosterone), as well as calcium channel
hepatic encephalopathy, and with improvement in
blockers (amlodipine), polyunsaturated lecithin, and a
serum bilirubin or decline in the MDF during the first
number of complementary and alternative medicines (re-
week of hospitalization—should be monitored closely,
viewed in O’Shea and McCullough224). In addition to
medical treatment directed at the underlying pathophys- but will likely not require nor benefit from specific
iologic abnormalities, several studies have tested other ag- medical interventions other than nutritional support
gressive interventions in patients with AH, such as a and abstinence (Class III, level A).
molecular adsorbent recirculating system.225 Although 11. Patients with severe disease (MDF score of
the results of early studies were optimistic, with better >32, with or without hepatic encephalopathy) and
than predicted outcomes in treated patients, a further case lacking contraindications to steroid use should be
series was less promising.226 Case reports have also de- considered for a four week course of prednisolone (40
scribed the outcome of patients with severe AH treated mg/day for 28 days, typically followed by discontinu-
with leukocytapharesis after failing to improve substan- ation or a 2-week taper) (Class I, level A).
tially on steroids.227,228 These reports are promising, but 12. Patients with severe disease (i.e., a MDF > 32)
recommendations regarding their appropriate use must could be considered for pentoxifylline therapy (400 mg
await results of comparative studies of outcomes in these orally 3 times daily for 4 weeks), especially if there are
patients. contraindications to steroid therapy (Class I, level B).
14. 320 O’SHEA, DARASATHY, AND MCCULLOUGH HEPATOLOGY, January 2010
Fig. 2. Proposed therapeutic algorithm for the long-term management of alcoholic liver disease.
VII. Long-Term Management of ALD reduce hospitalizations for infections over a 1-year peri-
od.231
A proposed algorithm for the management of ALD is Long-term aggressive nutritional therapy by the enteral
shown in Fig. 2. or oral route in patients with alcoholic cirrhosis is sup-
ported by studies that have shown improved nutritional
1. Nutritional Therapy status.232,233 Although controversial, this may possibly
Protein calorie malnutrition is common in ALD, is prevent complications of cirrhosis.195,234 Multiple feed-
associated with an increased rate of major complications ings, emphasizing breakfast and a nighttime snack, with a
of cirrhosis (infection, encephalopathy, and ascites), and regular oral diet at higher-than-usual dietary intakes (1.2-
indicates a poor prognosis.194 1.5 g/kg for protein and 35-40 kcal/kg for energy) seem
A total of 13 studies (seven randomized and six open- beneficial.235,236 Finally, during intermittent acute illness
label studies) have examined the effect of oral or enteral or exacerbations of the underlying chronic liver disease,
nutritional supplementation in patients with alcoholic above normal protein intake (1.5 g/kg body weight), and
cirrhosis, with interventions that ranged from 3 days to 12 kilocalorie intake (40 kcal/kg) improves protein calorie
months (reviewed in Stickel et al.229). Most of these stud- malnutrition,234 and should be considered in the treat-
ies are limited by small sample sizes and short durations of ment of these patients.
therapy. In one study, enteral feeding for 3-4 weeks in 35 Recommendation:
hospitalized, severely malnourished or decompensated 13. Patients with alcoholic cirrhosis should receive
patients with alcoholic cirrhosis seemed to improve sur- frequent interval feedings, emphasizing a night time
vival (P 0.065), hepatic encephalopathy, liver tests and snack and morning feeding, to improve nitrogen bal-
Child-Pugh score, as compared with controls receiving a ance (Class I, level A).
standard oral diet.197 In longer-term studies, equinitrog-
enous amounts of dietary branched chain amino acids 2. Medical Therapies
(BCAA) were compared with casein supplements for 3-6 A number of other agents have been tested in patients
months in patients with chronic hepatic encephalopa- with ALD. These include PTU, which was thought to
thy,230 and shown to improve encephalopathy, nitrogen decrease the hypermetabolic state induced by alco-
balance and serum bilirubin compared with casein. Sup- hol.237,238 A Cochrane review of 6 randomized controlled
plemental protein and 1000 kcal in decompensated pa- trials of PTU in alcoholic liver disease, with a total of 710
tients with alcoholic cirrhosis have also been shown to patients administered either PTU or placebo did not
15. HEPATOLOGY, Vol. 51, No. 1, 2010 O’SHEA, DARASATHY, AND MCCULLOUGH 321
show any benefit of PTU over placebo on the total or liver cantly influence the course of patients with alcoholic liver
related mortality, complications of liver disease or liver disease.254
histology in patients with alcoholic liver disease.239 A pos- Recommendations:
sible benefit of supplementation with S-adenosyl L-methi- 14. PTU and colchicine should not be used in the
onine (SAMe), a precursor to glutathione, has also been treatment of patients with ALD; SAMe should be used
studied extensively.240 One trial demonstrated a statisti- only in clinical trials (Class III, level A).
cally significant improvement in survival in patients with 15. The use of complementary or alternative med-
Childs A and B cirrhosis randomized to SAMe compared icines in the treatment of either acute or chronic
to placebo.241 Despite a strong theoretical rationale, and a alcohol-related liver disease has shown no convincing
number of supportive clinical trials,240,242 a Cochrane re- benefit and should not be used out of the context of
view of published data, based on nine randomized con- clinical trial (Class III, level A).
trolled trials with 434 patients in different stages of ALD,
did not demonstrate any significant benefit of SAMe on VIII. Liver Transplantation for ALD
total mortality, liver related mortality, complications or ALD is the second most common indication for liver
liver transplantation in patients with ALD.243 transplantation (LT) for chronic liver disease in the West-
Colchicine, which has both anti-inflammatory and an- ern world.255 Despite this, it is estimated that as many as
tifibrotic properties, has also been tested in alcoholic cir- 95% of patients with end-stage liver disease related to
rhosis after several small clinical trials, had suggested alcohol are never formally evaluated for candidacy for
improvement in fibrosis on serial liver biopsies in treated liver transplantation.256 This is attributed to perceptions
patients.244,245 However, a systematic meta analysis by the that ALD is self-induced, the possibility of recidivism or
Cochrane group of 15 randomized trials with 1714 pa- noncompliance, and the shortage of organs.179
tients (including patients with alcoholic fibrosis, alcoholic A 6-month period of abstinence has been recom-
hepatitis, and/or alcoholic cirrhosis as well as patients mended as a minimal listing criterion.257 This time period
with viral induced or cryptogenic fibrosis and/or cirrho- allows chemical dependency issues to be addressed; in
sis)246 showed no benefit of treatment on overall mortal- patients with recent alcohol consumption, it may also
ity, liver related mortality, liver tests or histology. In allow sufficient clinical improvement to make LT unnec-
addition, there was an increased risk of adverse effects essary. This requirement for a fixed abstinence period has
related to colchicine therapy. not been shown to accurately predict future drinking by
Emerging data suggest a role for TNF- mediated ap- alcoholic candidates for LT.258 Despite some data sug-
optosis in alcoholic hepatitis and, therapy targeting this gesting that patients with ALD were more ill at the time of
cytokine to inhibit apoptosis may be effective.247 Thalid- LT, and likely to have prolonged intensive care unit stays
omide, misoprostol, adiponectin and probiotics have and increased blood product requirements,259 overall sur-
been shown in preliminary reports to have anticytokine vival rates are generally similar between alcohol-related
properties.248-251 Although promising, these treatments and non–alcohol-related LT recipients.260
can not be considered as standard treatment for ALD and Patients who underwent LT for alcoholic liver disease
AH until further evidence of efficacy has been obtained. are highly likely to drink after transplantation.260 It has
been suggested that the consequences of alcohol use are
3. Complementary and Alternative Medicine minimal for many recipients, because the amounts con-
Treatment Options sumed are small and infrequent, but there are little reliable
Various alternative treatment options have been tested data to support this contention. Rates of recidivism be-
in the therapy of ALD. Silymarin, the presumed active tween 11%-49% (defined as any alcohol consumption
ingredient in milk thistle, is postulated to protect patients after transplantation) at 3-5 years after LT have been re-
from ALD on the basis of its antioxidant properties. Six ported.179,261 In general, however, only a small fraction of
published trials of the use of silymarin in patients with those who undergo liver transplantation for ALD revert to
ALD252 have tested its effects on normalizing liver tests heavy alcohol use or abuse.256 Poor follow-up and non-
and improving liver histology. One study suggested a pos- compliance with therapy are observed in only a minority
sible survival benefit compared to placebo.253 However, a of patients, and graft rejection rates are similar for patients
Cochrane systematic review and meta analysis of the 13 with ALD compared to those without ALD.255,260
published studies of silymarin in ALD and other liver An important issue that is still unresolved is the role of
diseases determined that the overall methodological qual- LT in patients with alcoholic hepatitis, who are generally
ity of the studies was low. Based on the few high quality excluded from transplant.257 In one study using retro-
trials, it was concluded that milk thistle does not signifi- spective histological analysis of the explanted liver, super-