The document summarizes guidelines for treating chronic hepatitis C. It discusses that hepatitis C virus infects 150-180 million people worldwide. Treatment aims to eradicate the virus and improve outcomes. Guidelines recommend treating all patients who are HCV RNA positive due to the natural progression of infection. Contraindications include decompensated cirrhosis and pregnancy. The goals of therapy are to eliminate HCV and slow disease progression to reduce risks like hepatocellular carcinoma. Sustained virological response is associated with improved outcomes like reduced liver-related mortality and cancer development.
This patient has chronic hepatitis C genotype 2 infection, hypertension, and GERD. He has fatigue and eye symptoms and a history of IV drug use suspected as the cause of his hepatitis C infection. His hepatitis C viral load is elevated and he has no cirrhosis. Treatment with 12 weeks of sofosbuvir and ribavirin is planned to achieve sustained virologic response and prevent progression of liver disease. His hypertension is also being monitored and managed.
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
This document discusses the long-term benefits of antiviral treatment for hepatitis B. It provides information on different phases of hepatitis B infection and when treatment is indicated. It also summarizes the approved antiviral drugs for treating chronic hepatitis B, including nucleoside analogs, nucleotide analogs, and cytokines. The document discusses the differences in lifecycles and mechanisms of HIV, HBV, and HCV. It then reviews the efficacy and resistance profiles of different antiviral drugs over time, highlighting the low resistance of tenofovir.
This document discusses hepatitis B and C virus (HBV, HCV) prevalence and treatment in the context of HIV coinfection. It provides the following key points:
1. HBV and HCV affect hundreds of millions of people globally, with higher prevalence in HIV-positive individuals. HIV exacerbates HBV disease progression and hampers HCV treatment.
2. Tenofovir is the recommended treatment for HBV in HIV coinfection, shown to be effective in clinical trials. Lamivudine has limitations due to resistance but may be used with tenofovir.
3. HCV treatment has advanced greatly with direct-acting antivirals like sofosbuvir and daclatasvir, achieving high
This document summarizes hepatitis C treatments and outreach efforts. It discusses current and upcoming antiviral treatments including simeprevir, sofosbuvir, and direct-acting antivirals. It also describes side effects of pegylated interferon and ribavirin treatments. The document estimates hepatitis C prevalence in Lambeth and the potential impact of untreated infection based on natural disease progression models. It overviews the antiviral therapy outreach service collaboration between Kings College Hospital and South London and Maudsley to engage patients in drug and alcohol centers through peer advocacy.
This study evaluated the safety and efficacy of pegylated interferon alpha-2a (PEG-IFN) monotherapy in 78 hepatitis C virus (HCV) positive hemodialysis patients. An early viral response was seen in 61.5% of patients at 12 weeks. However, only 19.2% had undetectable HCV RNA levels at end of treatment. A sustained viral response was achieved in 14.1% of the initial population. Adherence was poor, with 32% unable to complete the 48-week treatment due to adverse effects. Adverse events were common, occurring in 83% of patients. The incidence of serious adverse events was high at 0.19 per patient-year. The study
This document discusses hepatitis C recurrence after liver transplantation. It notes that hepatitis C recurrence is a major issue, accounting for two-thirds of graft loss. Five years post-transplant, 30% of patients have cirrhosis of the graft. The document examines factors that influence recurrence like fibrosis stage and viral load at one year post-transplant. It also discusses using antiviral treatment before and after transplant to improve outcomes.
This patient has chronic hepatitis C genotype 2 infection, hypertension, and GERD. He has fatigue and eye symptoms and a history of IV drug use suspected as the cause of his hepatitis C infection. His hepatitis C viral load is elevated and he has no cirrhosis. Treatment with 12 weeks of sofosbuvir and ribavirin is planned to achieve sustained virologic response and prevent progression of liver disease. His hypertension is also being monitored and managed.
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
This document discusses the long-term benefits of antiviral treatment for hepatitis B. It provides information on different phases of hepatitis B infection and when treatment is indicated. It also summarizes the approved antiviral drugs for treating chronic hepatitis B, including nucleoside analogs, nucleotide analogs, and cytokines. The document discusses the differences in lifecycles and mechanisms of HIV, HBV, and HCV. It then reviews the efficacy and resistance profiles of different antiviral drugs over time, highlighting the low resistance of tenofovir.
This document discusses hepatitis B and C virus (HBV, HCV) prevalence and treatment in the context of HIV coinfection. It provides the following key points:
1. HBV and HCV affect hundreds of millions of people globally, with higher prevalence in HIV-positive individuals. HIV exacerbates HBV disease progression and hampers HCV treatment.
2. Tenofovir is the recommended treatment for HBV in HIV coinfection, shown to be effective in clinical trials. Lamivudine has limitations due to resistance but may be used with tenofovir.
3. HCV treatment has advanced greatly with direct-acting antivirals like sofosbuvir and daclatasvir, achieving high
This document summarizes hepatitis C treatments and outreach efforts. It discusses current and upcoming antiviral treatments including simeprevir, sofosbuvir, and direct-acting antivirals. It also describes side effects of pegylated interferon and ribavirin treatments. The document estimates hepatitis C prevalence in Lambeth and the potential impact of untreated infection based on natural disease progression models. It overviews the antiviral therapy outreach service collaboration between Kings College Hospital and South London and Maudsley to engage patients in drug and alcohol centers through peer advocacy.
This study evaluated the safety and efficacy of pegylated interferon alpha-2a (PEG-IFN) monotherapy in 78 hepatitis C virus (HCV) positive hemodialysis patients. An early viral response was seen in 61.5% of patients at 12 weeks. However, only 19.2% had undetectable HCV RNA levels at end of treatment. A sustained viral response was achieved in 14.1% of the initial population. Adherence was poor, with 32% unable to complete the 48-week treatment due to adverse effects. Adverse events were common, occurring in 83% of patients. The incidence of serious adverse events was high at 0.19 per patient-year. The study
This document discusses hepatitis C recurrence after liver transplantation. It notes that hepatitis C recurrence is a major issue, accounting for two-thirds of graft loss. Five years post-transplant, 30% of patients have cirrhosis of the graft. The document examines factors that influence recurrence like fibrosis stage and viral load at one year post-transplant. It also discusses using antiviral treatment before and after transplant to improve outcomes.
Discussion of the current medications of chronic hepatitis treatment in the Egyptian market as well as our protocol of management in the Viral Hepatitis Treatment Centers in Egypt. Discussion of the latest recommendations of AASLD/IDSA and EASL are presented
March 192015talkforresidents final03232015 (1)katejohnpunag
This document provides an update on viral hepatitis and discusses two case studies. It begins by describing a 71-year-old male presenting with jaundice who is diagnosed with acute hepatitis A infection based on a reactive HAV IgM test. It then reviews hepatitis A virus and the diagnosis and management of acute hepatitis A. The second case discusses a 26-year-old male diagnosed with chronic hepatitis B infection based on positive HBsAg, anti-HBc IgM, and HBV DNA tests. The document concludes by discussing chronic hepatitis B infection and approved treatments.
Hospital Medicine Pearls, VA ACP Meeting 2014Jon Sweet
This document summarizes recent evidence from studies on various topics in hospital medicine:
1. For patients with atherosclerotic renal artery stenosis, renal artery stenting provides no benefit over optimal medical therapy alone and should not be performed.
2. For COPD exacerbations, a 5-day course of prednisone is as effective as the typical 14-day course with fewer steroid-related side effects.
3. Restrictive transfusion strategies (transfusing at Hb <7 g/dL) reduce mortality, rebleeding and complications compared to liberal strategies in patients with upper GI bleeding and acute MI.
4. For overt hepatic encephalopathy, rifaximin added to lactulose
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
This document discusses common mistakes made in diagnosing celiac disease and how to avoid them. It outlines 10 specific mistakes: 1) Evaluating patients for celiac disease after they have already started a gluten-free diet, 2) Diagnosing based only on symptom resolution after starting a gluten-free diet, and 3) Taking an insufficient number of biopsy samples or lacking biopsy orientation. The document provides details on each mistake and recommendations for proper diagnosis.
1. Chronic Hepatitis B (CHB) is caused by the HBV virus and can be either acute or chronic. It infects the liver and causes inflammation and necrosis.
2. Initial assessment of patients with CHB includes medical history, physical exam, liver disease markers and severity indicators, and testing of close contacts.
3. Treatment indications include elevated HBV DNA and ALT levels, cirrhosis, and family history of HCC. The preferred treatments are entecavir, tenofovir, and tenofovir alafenamide which have a high genetic barrier to resistance.
This document provides a summary of the methods used to develop recommendations for testing, managing, and treating hepatitis C virus (HCV) infection from the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA). An expert panel reviews evidence from various sources to develop recommendations that are rated based on strength. The guidance aims to provide up-to-date advice for healthcare providers as new therapies become available.
Recent guidelines in the management of chronic hepatitisShivshankar Badole
This document provides guidelines for the management of chronic hepatitis B (CHB) infection. It outlines the initial evaluation of HBsAg positive patients including laboratory tests and imaging/staging studies. It describes the phases of CHB infection and recommends treatment based on phase. Approved antiviral drugs are discussed along with monitoring on treatment. Treatment guidelines are provided for immune active CHB, immune tolerant CHB, HBeAg positive CHB that seroconvert, and HBeAg negative CHB. It also covers management of cirrhosis, viral breakthrough, pregnancy, and more.
This document discusses various types and classifications of pneumonia, including community acquired pneumonia (CAP), hospital acquired pneumonia (HAP), healthcare associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP). It then presents four clinical case studies of patients presenting with pneumonia and discusses the likely pathogens involved, appropriate testing, and treatment recommendations for each case. Key considerations included distinguishing between various pneumonia types and selecting initial empiric antibiotic therapy based on likely pathogens and patient risk factors or comorbidities.
Hepatitis (C) Story …. Past & Present & future
Most Recant Updating Guidelines by ASSLD & FDA
RAVS &How to deal with It ----12/7/2016.....
((Residents Lectures))
Adherence to treatment and quality of life during hepatitis C therapy:a prosp...Michel Rotily
Adherence to treatment and quality of life during hepatitis C therapy:a prospective, real-life, observational study by Patrick Marcellin, Michel Chousterman, Thierry Fontanges, Denis Ouzan, Michel Rotily, Marina Varastet,Jean-Philippe Lang, Pascal Melin and Patrice Cacoub, for the CheObs Study Group published in Liver Int 2011
This study evaluated a 12-week, all-oral, fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO regimen) in 415 noncirrhotic patients with chronic HCV genotype 1 infection. The primary outcome was sustained virologic response 12 weeks after treatment (SVR12) in treatment-naive patients (n=312). A key secondary outcome was SVR12 in treatment-experienced patients (n=103). Overall SVR12 was observed in 379 patients (91.3%), including 287 treatment-naive patients (92.0%) and 92 treatment-experienced patients (89.3%). The DCV-TRIO
This study evaluated the efficacy and safety of the combination of daclatasvir and sofosbuvir for 12 weeks or 8 weeks in previously untreated patients with HIV-HCV coinfection, and for 12 weeks in previously treated patients. Among previously untreated patients with HCV genotype 1, the rate of sustained virologic response was 96.4% for those treated for 12 weeks and 75.6% for those treated for 8 weeks. Rates of sustained virologic response across all genotypes were 97.0% for 12 weeks of treatment and 76.0% for 8 weeks. The most common side effects were fatigue, nausea, and headache, and there were no treatment discontinuations due to side effects. HIV viral suppression
This study assessed the efficacy and safety of the all-oral combination of daclatasvir plus asunaprevir for chronic hepatitis C virus genotype 1b infection. It included 307 treatment-naive patients, 205 previous non-responders to interferon-based therapy, and 235 patients ineligible or intolerant to interferon-based therapy. Treatment with daclatasvir plus asunaprevir for 12-24 weeks provided sustained virologic response in 90% of treatment-naive patients, 82% of previous non-responders, and 82% of ineligible/intolerant patients. The regimen was well tolerated with few serious adverse events or discontinuations across the cohorts. This study supports the use
D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 DuffusDSHS
The document discusses guidelines for initiating highly active antiretroviral treatment (HAART) based on CD4 count and viral load. Guidelines from 1998-2009 increasingly recommended treating HIV at higher CD4 counts and without a specific viral load threshold. Studies show the magnitude of CD4 increase is greatest when starting HAART at low counts, but normalization is more likely the earlier therapy begins. A CD4 count below 350 cells/mm3 increases the risk of cardiovascular and other non-AIDS complications.
This document discusses strategies for screening, diagnosing, and treating hepatitis B virus (HBV) infection. It notes that around 400 million people worldwide have chronic HBV infection, and 500,000 die yearly from related complications like cirrhosis and liver cancer. Proper identification of infected individuals and assessment of disease status is important to reduce the disease burden and optimize treatment outcomes. Initial evaluation of patients with chronic HBV should include medical history, physical exam, liver biopsy if needed, and laboratory tests of liver function and HBV markers. Monitoring HBV DNA levels and liver enzymes over time is also important for assessing disease status and treatment response.
A power point presentation on Hepatitis C virus on epidemiology, presentation, diagnosis and current treatment strategies we are practicing in BSMMU at a international standerd.
1) The document outlines the consensus approach to managing non-variceal upper GI bleeding, including risk stratification, endoscopic treatment, and the role of PPIs.
2) Early endoscopy within 24 hours allows for safe discharge of low risk patients and improves outcomes for high risk patients through endoscopic hemostasis.
3) Combination endoscopic therapy with injection followed by thermal treatment is the most effective approach for achieving hemostasis.
4) High dose intravenous PPIs reduce recurrent bleeding rates and improve mortality when used in conjunction with endoscopic hemostasis in patients with high risk stigmata.
The document discusses the risks of upper gastrointestinal adverse effects from NSAID use. It summarizes that:
1) NSAIDs can cause gastric mucosal damage through inhibition of both COX-1 and COX-2 enzymes and their topical irritant effects.
2) NSAID-associated gastroduodenal damage is dependent on gastric luminal pH, with more damage occurring at lower pH levels.
3) NSAID use is associated with increased risks of upper GI symptoms like dyspepsia, peptic ulcers, and complications from ulcers like bleeding. COX-2 selective NSAIDs still carry risks, especially in high-risk patients.
4) Upper GI side effects from
Discussion of the current medications of chronic hepatitis treatment in the Egyptian market as well as our protocol of management in the Viral Hepatitis Treatment Centers in Egypt. Discussion of the latest recommendations of AASLD/IDSA and EASL are presented
March 192015talkforresidents final03232015 (1)katejohnpunag
This document provides an update on viral hepatitis and discusses two case studies. It begins by describing a 71-year-old male presenting with jaundice who is diagnosed with acute hepatitis A infection based on a reactive HAV IgM test. It then reviews hepatitis A virus and the diagnosis and management of acute hepatitis A. The second case discusses a 26-year-old male diagnosed with chronic hepatitis B infection based on positive HBsAg, anti-HBc IgM, and HBV DNA tests. The document concludes by discussing chronic hepatitis B infection and approved treatments.
Hospital Medicine Pearls, VA ACP Meeting 2014Jon Sweet
This document summarizes recent evidence from studies on various topics in hospital medicine:
1. For patients with atherosclerotic renal artery stenosis, renal artery stenting provides no benefit over optimal medical therapy alone and should not be performed.
2. For COPD exacerbations, a 5-day course of prednisone is as effective as the typical 14-day course with fewer steroid-related side effects.
3. Restrictive transfusion strategies (transfusing at Hb <7 g/dL) reduce mortality, rebleeding and complications compared to liberal strategies in patients with upper GI bleeding and acute MI.
4. For overt hepatic encephalopathy, rifaximin added to lactulose
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
This document discusses common mistakes made in diagnosing celiac disease and how to avoid them. It outlines 10 specific mistakes: 1) Evaluating patients for celiac disease after they have already started a gluten-free diet, 2) Diagnosing based only on symptom resolution after starting a gluten-free diet, and 3) Taking an insufficient number of biopsy samples or lacking biopsy orientation. The document provides details on each mistake and recommendations for proper diagnosis.
1. Chronic Hepatitis B (CHB) is caused by the HBV virus and can be either acute or chronic. It infects the liver and causes inflammation and necrosis.
2. Initial assessment of patients with CHB includes medical history, physical exam, liver disease markers and severity indicators, and testing of close contacts.
3. Treatment indications include elevated HBV DNA and ALT levels, cirrhosis, and family history of HCC. The preferred treatments are entecavir, tenofovir, and tenofovir alafenamide which have a high genetic barrier to resistance.
This document provides a summary of the methods used to develop recommendations for testing, managing, and treating hepatitis C virus (HCV) infection from the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA). An expert panel reviews evidence from various sources to develop recommendations that are rated based on strength. The guidance aims to provide up-to-date advice for healthcare providers as new therapies become available.
Recent guidelines in the management of chronic hepatitisShivshankar Badole
This document provides guidelines for the management of chronic hepatitis B (CHB) infection. It outlines the initial evaluation of HBsAg positive patients including laboratory tests and imaging/staging studies. It describes the phases of CHB infection and recommends treatment based on phase. Approved antiviral drugs are discussed along with monitoring on treatment. Treatment guidelines are provided for immune active CHB, immune tolerant CHB, HBeAg positive CHB that seroconvert, and HBeAg negative CHB. It also covers management of cirrhosis, viral breakthrough, pregnancy, and more.
This document discusses various types and classifications of pneumonia, including community acquired pneumonia (CAP), hospital acquired pneumonia (HAP), healthcare associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP). It then presents four clinical case studies of patients presenting with pneumonia and discusses the likely pathogens involved, appropriate testing, and treatment recommendations for each case. Key considerations included distinguishing between various pneumonia types and selecting initial empiric antibiotic therapy based on likely pathogens and patient risk factors or comorbidities.
Hepatitis (C) Story …. Past & Present & future
Most Recant Updating Guidelines by ASSLD & FDA
RAVS &How to deal with It ----12/7/2016.....
((Residents Lectures))
Adherence to treatment and quality of life during hepatitis C therapy:a prosp...Michel Rotily
Adherence to treatment and quality of life during hepatitis C therapy:a prospective, real-life, observational study by Patrick Marcellin, Michel Chousterman, Thierry Fontanges, Denis Ouzan, Michel Rotily, Marina Varastet,Jean-Philippe Lang, Pascal Melin and Patrice Cacoub, for the CheObs Study Group published in Liver Int 2011
This study evaluated a 12-week, all-oral, fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO regimen) in 415 noncirrhotic patients with chronic HCV genotype 1 infection. The primary outcome was sustained virologic response 12 weeks after treatment (SVR12) in treatment-naive patients (n=312). A key secondary outcome was SVR12 in treatment-experienced patients (n=103). Overall SVR12 was observed in 379 patients (91.3%), including 287 treatment-naive patients (92.0%) and 92 treatment-experienced patients (89.3%). The DCV-TRIO
This study evaluated the efficacy and safety of the combination of daclatasvir and sofosbuvir for 12 weeks or 8 weeks in previously untreated patients with HIV-HCV coinfection, and for 12 weeks in previously treated patients. Among previously untreated patients with HCV genotype 1, the rate of sustained virologic response was 96.4% for those treated for 12 weeks and 75.6% for those treated for 8 weeks. Rates of sustained virologic response across all genotypes were 97.0% for 12 weeks of treatment and 76.0% for 8 weeks. The most common side effects were fatigue, nausea, and headache, and there were no treatment discontinuations due to side effects. HIV viral suppression
This study assessed the efficacy and safety of the all-oral combination of daclatasvir plus asunaprevir for chronic hepatitis C virus genotype 1b infection. It included 307 treatment-naive patients, 205 previous non-responders to interferon-based therapy, and 235 patients ineligible or intolerant to interferon-based therapy. Treatment with daclatasvir plus asunaprevir for 12-24 weeks provided sustained virologic response in 90% of treatment-naive patients, 82% of previous non-responders, and 82% of ineligible/intolerant patients. The regimen was well tolerated with few serious adverse events or discontinuations across the cohorts. This study supports the use
D1 Highly Active Antiretroviral Treatment (HAART) DHHS Guidelines 2009 DuffusDSHS
The document discusses guidelines for initiating highly active antiretroviral treatment (HAART) based on CD4 count and viral load. Guidelines from 1998-2009 increasingly recommended treating HIV at higher CD4 counts and without a specific viral load threshold. Studies show the magnitude of CD4 increase is greatest when starting HAART at low counts, but normalization is more likely the earlier therapy begins. A CD4 count below 350 cells/mm3 increases the risk of cardiovascular and other non-AIDS complications.
This document discusses strategies for screening, diagnosing, and treating hepatitis B virus (HBV) infection. It notes that around 400 million people worldwide have chronic HBV infection, and 500,000 die yearly from related complications like cirrhosis and liver cancer. Proper identification of infected individuals and assessment of disease status is important to reduce the disease burden and optimize treatment outcomes. Initial evaluation of patients with chronic HBV should include medical history, physical exam, liver biopsy if needed, and laboratory tests of liver function and HBV markers. Monitoring HBV DNA levels and liver enzymes over time is also important for assessing disease status and treatment response.
A power point presentation on Hepatitis C virus on epidemiology, presentation, diagnosis and current treatment strategies we are practicing in BSMMU at a international standerd.
1) The document outlines the consensus approach to managing non-variceal upper GI bleeding, including risk stratification, endoscopic treatment, and the role of PPIs.
2) Early endoscopy within 24 hours allows for safe discharge of low risk patients and improves outcomes for high risk patients through endoscopic hemostasis.
3) Combination endoscopic therapy with injection followed by thermal treatment is the most effective approach for achieving hemostasis.
4) High dose intravenous PPIs reduce recurrent bleeding rates and improve mortality when used in conjunction with endoscopic hemostasis in patients with high risk stigmata.
The document discusses the risks of upper gastrointestinal adverse effects from NSAID use. It summarizes that:
1) NSAIDs can cause gastric mucosal damage through inhibition of both COX-1 and COX-2 enzymes and their topical irritant effects.
2) NSAID-associated gastroduodenal damage is dependent on gastric luminal pH, with more damage occurring at lower pH levels.
3) NSAID use is associated with increased risks of upper GI symptoms like dyspepsia, peptic ulcers, and complications from ulcers like bleeding. COX-2 selective NSAIDs still carry risks, especially in high-risk patients.
4) Upper GI side effects from
This document lists the top locations on Instagram in 2013, which included major shopping malls, landmarks, and tourist destinations in cities like Bangkok, New York, Las Vegas, Los Angeles, and Orlando. Live photo links are provided for each location's Instagram photos from that year.
Japanese encephalitis is a mosquito-borne viral disease that infects horses, pigs, and humans. It is caused by the Japanese encephalitis virus, a flavivirus transmitted primarily by Culex mosquitoes. The disease is endemic in parts of Asia and the Pacific. Birds act as the natural reservoir host and pigs amplify the virus. Humans and horses are dead-end hosts and can experience neurological symptoms. There is no treatment for the virus and vaccination is the most effective way to prevent disease in humans and animals.
Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by the bacteria Mycobacterium leprae. It primarily affects the nerves, skin, and mucous membranes of the body. The disease is transmitted through droplets from the nose and mouth of infected individuals during close and frequent contact. Symptoms include skin lesions and loss of sensation. Leprosy is classified based on clinical features into paucibacillary or multibacillary types. Diagnosis involves examination of skin and nerve lesions along with skin smears. Treatment involves multidrug therapy to cure the disease and prevent nerve damage and disability.
32 Ways a Digital Marketing Consultant Can Help Grow Your BusinessBarry Feldman
How can a digital marketing consultant help your business? In this resource we'll count the ways. 24 additional marketing resources are bundled for free.
The document provides guidance on treating hepatitis C, defining sustained virologic response, identifying appropriate treatment candidates, and differentiating treatment by genotype. It discusses factors that affect treatment response, common side effects of treatment medications like peginterferon and ribavirin, and screening and monitoring processes during treatment. The future of hepatitis C treatment involves adding protease inhibitors telaprevir or boceprevir to peginterferon and ribavirin regimens.
This document discusses advances in treatment for hepatitis C virus (HCV) infection. It provides information on:
- The primary goals of HCV treatment as viral eradication and prevention of liver disease progression.
- Definitions of sustained virological response (SVR) and response rates achieved with pegylated interferon and ribavirin treatment.
- New direct-acting antiviral drugs in development that target specific steps in the HCV lifecycle, including protease, polymerase, and NS5A inhibitors.
Antinuclear antibody positivity in chronic hepatitis c patientsRashed Hassen
This study aimed to evaluate the significance of antinuclear antibody (ANA) positivity in chronic hepatitis C patients and its impact on histopathology and early virological response to antiviral therapy. The study found that ANA positivity was associated with more advanced liver fibrosis but did not affect treatment response rates. While ANA levels increased in most ANA-positive patients during therapy, this increase correlated with achieving early virological response. Overall, ANA positivity alone did not predict treatment outcome, and independent predictors of response were body mass index, fibrosis stage, ALT levels, and viral load.
The document provides information on the management of Hepatitis B. It discusses the virology of HBV, epidemiology, natural history, goals of treatment, criteria for treatment, treatment options and monitoring. Key points include:
- HBV is a DNA virus that causes both acute and chronic hepatitis. Approximately 240 million people globally have chronic HBV infection.
- Natural history depends on when infection is acquired. Risk of chronic infection is highest with infection at birth.
- Treatment goals are to prevent progression of disease and development of complications like cirrhosis and liver cancer.
- Treatment is recommended for those with HBeAg-positive chronic hepatitis B with HBV DNA >20,000 IU/mL and elevated
This document discusses factors related to prognosis in patients co-infected with HIV and hepatitis C virus (HCV) based on results from the HEPAVIH cohort study. It finds that FibroScan score, albumin levels, platelet count, and age are independently associated with risk of liver complications or liver-related death. The risk of any complication or death from any cause is estimated at 10% after 5 years. Liver disease accounted for 27% of deaths. Effective treatment of HIV and HCV can reduce liver-related mortality in co-infected patients.
This document discusses the management of variceal bleeding, specifically focusing on esophageal and gastric varices. It provides an overview of endoscopic and medical therapies for controlling acute esophageal variceal bleeding such as endoscopic band ligation, sclerotherapy, and pharmacologic therapies like octreotide. For gastric varices, it describes different classification systems and challenges in managing bleeding, noting endoscopic therapies like sclerotherapy, ligation, and glue injection can control acute bleeding but have high rebleeding risks. It emphasizes a multidisciplinary approach is often needed for gastric variceal management.
1) A 29-year-old woman presented with jaundice, abdominal pain, and nausea/vomiting. Her liver enzymes were elevated and ultrasound showed a normal liver. She was diagnosed with acute hepatitis A.
2) A 38-year-old man with a history of elevated liver enzymes presented with mildly elevated enzymes. He tested positive for hepatitis B and C markers, indicating chronic hepatitis C infection.
3) Hepatitis C is a major cause of liver disease in the US, infecting an estimated 4 million people, with 30,000 new infections annually and 12,000-15,000 deaths from hepatitis C each year.
This document summarizes a seminar on the management of hepatitis C. It discusses the virology of hepatitis C virus and outlines guidelines for patient evaluation, counseling, and antiviral therapy. The summary focuses on the evolution of hepatitis C treatment from interferon-based regimens to highly effective all-oral direct-acting antiviral combination therapies that achieve over 95% cure rates.
BCC4: Pierre Janin on 4 Newer Agents for Hepatitis CSMACC Conference
Janin speaks on the dawn of a revolution for treating Hepatitis C. This was recorded at Bedside Critical Care Conference 4. Full postings can be found at www.intensivecarenetwork.com
Hepatitis C is a global problem caused by the hepatitis C virus (HCV). HCV is a blood-borne virus that infects approximately 200 million people worldwide. Laboratory testing plays an important role in diagnosing HCV, evaluating patients for treatment, monitoring patients during treatment, and following up after treatment. There are 6 major genotypes of HCV with genotypes 1 and 4 being more difficult to treat and less responsive to interferon-based therapy.
This document provides information about hepatitis, including its definition, causes, history, clinical features, and treatments. The main causes of hepatitis include viral hepatitis from hepatotropic viruses like HAV, HBV, HCV, HDV, and HEV, as well as non-infectious causes like alcohol, drugs, autoimmune reactions, and metabolic disorders. The document describes the characteristics of different viral hepatitises and recommendations for evaluation, prevention, and treatment of acute and chronic hepatitis.
Hepatitis C is a global health problem that causes 700,000 deaths per year. In Bangladesh, 1% of the population has HCV. New guidelines recommend screening high-risk groups and treating with direct-acting antiviral drugs, which have cure rates over 90% and shorter treatment durations compared to previous interferon-based regimens. Proper treatment can prevent cirrhosis, liver cancer and death from HCV. While challenges remain, scientists hope to eliminate HCV globally by 2030 with new pan-genotypic drugs. Prevention through injection safety, screening blood products, and educating healthcare workers is also important to control the disease.
HBV has been associated with humans for over 1,000 years. Recent evidence from a mummified Korean child who tested positive for HBV DNA establishes that HBV has been present in humans for at least 500 years. Treatment guidelines recommend antiviral therapy for patients with chronic HBV based on HBV DNA levels and ALT levels. Tenofovir and entecavir are preferred first-line treatments due to their superior efficacy, tolerability and low resistance profiles. Long-term antiviral therapy can reduce the risk of liver decompensation, hepatocellular carcinoma, and death in patients with chronic HBV.
This document discusses the management of cirrhosis of the liver to improve survival. It defines cirrhosis as a chronic progressive disease characterized by degeneration and destruction of liver cells. Major causes include alcohol, viral hepatitis, and unknown causes. Complications can include ascites, jaundice, hepatic encephalopathy, and bleeding varices. Prognosis is assessed using scoring systems like Child-Pugh and MELD scores. Management involves treating the underlying cause, managing complications, nutrition support, and procedures like TIPS or liver transplant if needed. Specific treatments are discussed for conditions like alcoholic cirrhosis, viral hepatitis B and C, and autoimmune hepatitis.
The document discusses human immunodeficiency virus (HIV) including its epidemiology, transmission, clinical presentation, diagnostics, lifecycle, treatment goals, and antiretroviral therapy options. It provides details on the natural history of HIV infection and progression to AIDS if left untreated, as well as factors that influence disease progression. Guidelines for initiating antiretroviral therapy and recommendations for initial treatment regimens are summarized.
The document provides information on the diagnosis and management of autoimmune hepatitis. It discusses the epidemiology, pathogenesis, clinical presentations, diagnostic criteria, investigations including liver biopsy, and treatment approaches. Some key points include:
- There are two peaks of onset, in the second decade and 50-60 years of age. It predominantly affects females.
- Diagnosis is one of exclusion and relies on scoring systems like the revised IAIHG criteria to determine definite or probable autoimmune hepatitis.
- Liver biopsy can help diagnose, exclude other causes, monitor disease, and assess response to treatment. Histological features include interface hepatitis and lymphocytic infiltration.
- Treatment involves immunosuppression with corticosteroids and azath
This document discusses HIV and hepatitis C, and how treatment has improved outcomes. It presents two case studies of patients with advanced HIV presenting with opportunistic infections who were successfully treated. It also summarizes research showing that early antiretroviral therapy improves survival for patients with HIV/AIDS or opportunistic infections like PCP, and that cure of hepatitis C through direct-acting antivirals reduces mortality and complications like liver cancer. While treatment access has increased globally, challenges remain in testing and treating all those in need.
This study evaluated the efficacy and safety of a 12-week, all-oral, fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir for the treatment of chronic hepatitis C virus genotype 1 infection in noncirrhotic patients. The study found high rates of sustained virologic response at 12 weeks post-treatment (SVR12) in both treatment-naive (92.0%) and treatment-experienced (89.3%) patients. Adverse events were generally mild and few led to treatment discontinuation. The results demonstrate that this ribavirin-free, direct-acting antiviral regimen achieved high SVR12 rates in noncirrhotic patients with
Similar to Guidelines hep c palestine may 2010 (20)
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Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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Guidelines hep c palestine may 2010
1. The First Congress of the Palestinian Society of Gastroenterology (20-22) May 2010
Recent guidelines/strategies in
chronic hepatitis C therapy
Antonio Ascione MD
Consultant Hepatologist
Center for liver diseases
Fatebenefratelli Hospital
Naples - ITALY
2. The overall prevalence, according to
the WHO, is around 3%
(range 1–10%).
Hepatitis C virus (HCV) infection is a
worldwide problem with at least 150–180
million of people chronically infected.
3. Outcomes of HCV Infection
100 acute HCV infections
20% recovery 80% persistent infections
20 patients 80 patients
Alcohol 30% stable, chronic, 40% variable 30% severe
HBV nonprogressive progression progressive hepatitis
HIV
Iron 24 patients 32 patients 24 patients
Steatosis
Antiviral therapy
56 patients
End-stage disease, HCC, Treatment Sustained
liver transplantation, failure (~40%) response (~60%)
death
13% LIVER RELATED 22 patients 34 patients
DEATHS IN 20 YRS
4. Development of therapies for HCV chronic
hepatitis (SVR)
66%
Achille’s heel of guidelines:
• Fixed dose of the drugs
• Fixed lenght of treatment
• Characteristics of host response not
taken into consideration
5. Which Patients Should Be Treated ?
X
HCV carriers older than 65y NO / YES
HCV carriers with normal ALT NO / YES
HCV carriers with abnormal ALT
• Mild histology NO / YES
Decision should depend on:
- Age < 40-45 yrs
- ALT profile > x 3 - 4
- Histologic activity
- HCV Genotype 2/3
• Moderate / severe YES
6. LONG-TERM OUTCOME AFTER ANTIVIRAL
THERAPY OF DECOMPENSATED CIRRHOTIC
PATIENTS WITH HEPATITIS C VIRUS INFECTION
IACOBELLIS Angelo, et al.
Division of Gastroenterology and Digestive Endoscopy,
“Casa Sollievo della Sofferenza” Hospital, IRCCS, S. Giovanni Rotondo
Results. Among 75 treated patients, 24 individuals (32%) achieved an SVR.
Conclusions. In cirrhotic patients secondary to HCV infection who have
progressed to a stage of liver decompensation, attaining an SVR
after antiviral therapy has a substantial positive impact on
the long-term prognosis.
Accepted as oral presentation,
MASL First meeting, Napoli (ITALY), June 13-15,2010
7. Typical exclusion criteria in RCTs of therapy
in chronic hepatitis C
Age> 65 yrs Depression
Low hemoglobin (<12 g/dl) Psychiatric disease
Low WBC count (<3,000/mm3) Coronary artery dis
Neutropenia (<1,500/mm3) Cerebrovascular dis
Thrombocytopenia (< 100,000/ Neurologic illness
mm3) Seizure disorders
Decompensated liver disease Alcohol abuse
Bilirubin >2.0 mg/dL IV drug use
Albumin <3.5 g/dL Methadone treatment
Prothr time >2 sec prolonged Hemophilia
Creatinine >1.5 mg/dL Hemoglobinopathy
Alphafetoprotein >50 mg/dL Autoimmunity
HBsAg+ Thyroid diseases
Any other known liver disease Institutionalization
8. Schedules for Naive
Patients
PEG-IFN α2a 180 μg/week or
HCV - 1/4
Ribavirin 1000 (</=75 Kg) - 1.200 (>75 Kg) / d
x 48 weeks
TREATMENT MUST BE
PEG-IFN α2b 1.5 µg/Kg/wk
PERSONALIZED AND
Ribavirin 800/1400 according body weight
GUIDED BY THE
HCV - 2/3 RESPONSE TO THERAPY
PEGs same dosages, less ribavirin
x 24 weeks
DURATION: shorter ? Longer ?
11. Which patient must be
treated?
All those who show signs of progressive
liver disease and have no
contraindications to the treatment
(Consensus NIH, EASL, APASLD, AISF)
All patients HCV-RNA positive should be
evaluated for therapy because of the
natural history of HCV chronic infection
12. HIPPOCRATES
(Kos ~460 - Larissa~ 377 B.C.)
PRIMUM
NON
NOCERE
A fundamental medical precept: first do not harm
13. CONTRAINDICATIONS
PEG-IFN
Autoimmune liver diseases
IN decompensation in patients with cirrhosis
Hepatic
FEMALE UNDER THERAPY
Neonates and infants
CHECK MONTLY
Hypersensitivity
THE PREGNANCY TEST
PEG-IFN PLUS RIBAVIRIN
Pregnant women
Men whose partners are pregnant
Hemoglobinopathies (thalassemia)
Hypersensitivity
14. WARNINGS
PEGINTERFERON CAN CAUSE
May cause or aggravate fatal or life-threatening neuropsychiatric,
autoimmune, ischemic, and infectious disorders. Monitor closely with
periodic clinical and laboratory evaluations and withdraw therapy in
patients with persistently severe or worsening signs or symptoms of these
conditions
RIBAVIRIN CAN CAUSE
Hemolytic anemia. The anemia associated with ribavirin therapy may
result in a worsening of cardiac disease
Ribavirin is genotoxic and mutagenic and should be considered a potential
carcinogen
Ribavirin may cause birth defects and/or death of the fetus. Extreme care
must be taken to avoid pregnancy in female patients and in female
partners of male patients
Ribavirin is not effective as monotherapy
15. Side effects
Nearly all patients experience one or more AE
Most common are: flu like syndrome, fatigue,
The patientarthralgias, insommia,
pyrexia, myalgia, headache,
should
know everything
anorexia, ansiety, depression, irritability,
psychiatric reactions
since the beginning
Other common symptoms are: anorexia, nausea,
vomiting, diarrea, pruritus, alopecia, injection site
reactions
16. Goals of Therapy in HCV hepatitis
• Primary goal
– Eradicate HCV infection SVR
• Secondary goals
– Slow disease progression
– Improve histology
– Reduce risk of hepatocellular carcinoma
– Improve health-related quality of life
Lindsay et al. Hepatology. 2002;36:S114-S120.
17. Sustained virological response to
interferon-alpha is associated
with improved outcome in HCV-
related cirrhosis: a retrospective
study.
S. Bruno, T. Stroffolini, S. Bollani, A. Ascione,
G. Mazzella, L. Benvegnù, A. Mangia, P Andreone,
M. Persico, G. F. Gaeta, P. Almasio on behalf of the
AISF Group
HEPATOLOGY 2007;45:579-87.
18. Kaplan Meier curves of liver-related mortality
according to the achievement of SVR
1,0 SVR
,8
No SVR
p<0.001 by Log Rank test
,6
,4
,2
0,0
0 24 48 72 96 120 144 168
Patients at risk months
SVR 199 194 185 173 118 73 23
19. Kaplan Meier curves of HCC development
according to the achievement of SVR
1,0
Surveillance is
,8 mandatory for these
subjects
,6
p<0.001 by Log Rank test
,4
No SVR
,2
SVR
0,0
0 24 48 72 96 120 144 168
Patients at risk months
SVR 199 194 185 173 117 72 21
20. Survival
Sustained virological responders
p=0.02 log rank test
Survival probability (%)
Treatment failure
MONTHS
Picciotto FP et al, J Hepatol. 2007;46:459-65.
21. Effects of IFN Treatment on HRQOL
Baseline to 48-week mean changes
30
25 Virologic Responders (41) Virologic Non Responders (396)
20
15
10
5
0
Phys. Role-ph. Bodily Gen. Vitality Soc. Role emot. Mental
Funct. pain Health Funct. Health
(Multicenter Italian Study, 2004)
22. Histological Response Among
Sustained Virological Responders
100
83%
Histological Response (%)
79%
80
62 / 75
Patients With
19 / 24 P = 0.76
60
40
20
0
IFN α-2a PEG (40kDa) IFN α-2a
3 MIU 180 µg
J. Heathcote et al, NEJM, 2000
23. The effect of peginterferon α-2a on liver histology in chronic
hepatitis C: a meta analysis of individual patients data
Subgroup analysis of patients with cirrhosis (n=198)
66.1%
4 4
Before 3 24.2% 3 3 After
1 9.6 % 1 1
0 0% 0 0
SVR the only predictor for staging improvement
Cammà et al, Hepatology, 2004
27. Short term reponse of HCV-RNA to IFN
Direct
antiviral Immune
action Clearance
Null-responder
Serum HCV RNA
1st phase Flat partial responder
Slow partial responder
2nd phase
detection limit
0 1 2 3 7 14 21 28
Days Rapid virological responder
or SUPERESPONDERS
28. Patterns of Virological Response
Initial Response to
Post treatment observation
response treatment
HCV RNA
“Nonresponse”
Based on EVR
Complete EVR (cEVR)
RVR EVR LLD
Partial EVR (pEVR)
SVR
WEEKS 0 1 4 12 18 24 48
72
Modified from Pawlotsky JM, Hepatology vol. 32, #5, 2000
29. New Definitions of Response to
Treatment
Rapid Virologic
HCV RNA undetectable by Week 4
Response (RVR)
Early Virologic
≥ 2 log decline in HCV RNA by Week 12
Response (EVR)
End of Treatment
Undetectable HCV RNA at end of treatment
(EOT) Response
Partial Virologic ≥ 2 log decline in HCV RNA by Week 12, but HCV
Response RNA detectable at Week 24
Sustained
Virologic HCV RNA negativity 12-24 weeks after treatment end
Response (SVR)
30.
31. Quantitative HCV-RNA (IU/mL) Tests
Dynamic Ranges of Assays
SuperQuant™
100 copies/mL 100 million copies/mL
ROCHE
COBAS
TaqMan™ 15 IU/mL 100 million IU/mL
HCV Test
Roche COBAS AMPLICOR™
HCV MONITOR Test, v2.0 600 IU/mL 500 000 IU/mL
Roche AMPLICOR HCV
MONITOR® Test, v2.0 600 IU/mL 850 000 IU/mL
Bayer bDNA 3.0 615 IU/mL 7.7 million IU/mL
Disclaimer: Information on this slide represents my opinions, not those of Roche
32. RVR is an Important Predictor of SVR
• Methods
− Subanalysis of 3 phase III trials:
ACCELERATE, Fried, Hadziyannis
− 1.383 patients treated for 24 (G2/3) or 48
(G1/4) weeks with Pegasys 180 mcg/wk plus
ribavirin 800 mg/d (G2/3) or 1.000/1.2000 mg/d
(G1/4)
Fried WW et al, presented at EASL 2008, April 23-27, 2008, Milan, Italy, Abstract #7
33.
34.
35.
36.
37. STOPPING RULES TELL YOU
TO STOP TREATMENT IF AT
W12
HCV-RNA IS STILL POSITIVE
38.
39. Why an RVR/EVR-guided Approach Makes Sense
● Simplification of treatment in pts with a
good prognostic profile (=RVR)
● Intensification of treatment in pts with a
poor prognostic profile (non-RVR + EVR)
● Motivation of patients achieving early
responses
40. HOW CAN WE OBTAIN
BETTER RESULTS?
• PAY ATTENTION TO THE BAD
FRIENDS
• ADHERENCE TO PRESCRIBED
THERAPY
• RIBAVIRIN ANEMIA AND
LEUKOPENIA
• TREAT SIDE EFFECTS!
41. BAD FRIENDS
• ALCOHOL
• OVERWEIGHT
• IRON
• STEATOSIS
• METABOLIC DISORDERS
44. How can we improve treatment
outcomes?
Identify and
Genotype is the most important
manage predictors
of poor response
baseline predictor of response
Use on-treatment 1. Response-guided therapy (RGT)
predictors of
2. Optimisation of ribavirin dosing
response and
optimise ribavirin
Treatment options for
New strategies
non-responders
Future strategies New molecules
46. CONCLUSIONS
• Safety comes first! Check contraindications.
• Follow carefully the patient for side effects:
don’t reduce/stop therapy too early: don’t
run away. Compliance is crucial.
• Follow the on-treatment virological response
in order to decide the duration of therapy
• RVR is highly predictive of success.
• Use an appropriate test for HCV-RNA
quantification.
• Optimize the treatment with the drugs now
available (PEG+RIBA).
47. Island of Procida (Napoli - ITALY)
CorricellaFisherman’s Port at sunrise
Materiale per Roma
Grazie
49. PEGINTERFERON PLUS RIBAVIRIN
IS THE STANDARD OF CARE FOR
HCV CRHONIC INFECTION
Many side effects:
Anemia caused by Ribavirin and PEG-IFN
Neutropenia caused by PEG-IFN
Thrombocytopenia caused by PEG-IFN
50. SYMPTOMS ASSOCIATED WITH:
• Anemia
– Fatigue, impaired QoL, and reduced adherence
– Can increase risk of myocardial ischemia, other
cardiovascular abnormalities
• Higher risk in patients with chronic obstructive pulmonary disease
• Neutropenia
– Can predispose to infection (very rare in
immunocompetent)
• Thrombocytopenia
– Can predispose to bleeding (very rare)
52. General Guidelines for RBV Dose Reduction
or Discontinuation
Laboratory Manufacturer Package Insert
values
Recommendations
Hemoglobin
No change in RBV dose if patient has minimal symptoms
< 11.0 but
> 10 g/dL In a symptomatic anemic patient, consider RBV dose reduction by
200 mg/day and/or starting an erythropoietic growth factor
Decrease RBV by 200 mg/day and/or consider starting an erythropoietic
< 10.0 but growth factor
> 8.5 g/dL Recheck hemoglobin levels at least every 2 wks or more frequently if
indicated
< 8.5 g/dL Discontinue until resolution
In patients with stable underlying cardiac disease, reduce
ribavirin by 200 mg/day if ≥ 2 g/dL drop in hemoglobin occurs
over a 4-week period. If the hemoglobin level is < 12 g/dL
after 4 weeks of dose reduction, discontinue RBV until
resolution and reevaluation.
53. Laboratory Values Manufacturer Package Insert Recommendations
LABORATORY MANUFACTURER PACKAGE INSERT
VALUES RECOMMENDATIONS
White blood cell count
< 1.5 x 109/L PegIFN alfa-2b: reduce dose by 50% and re-evaluate
< 1.0 x 109/L PegIFN alfa-2b: discontinue until resolution
Absolute neutrophil count
PegIFN alfa-2a: reduce dose to 135 µg/wk and re-evaluate
< 0.75 x 109/L
PegIFN alfa-2b: reduce dose by 50% and re-evaluate
< 0.50 x 109/L PegIFN alfa or cIFN: discontinue until resolution
Platelet count
< 80,000/mm3 PegIFN alfa-2b: reduce dose by 50% and re-evaluate
PegIFN alfa-2a: reduce dose to 90 µg/wk and re-evaluate
< 50,000/mm3
PegIFN alfa-2b or cIFN: discontinue until resolution
< 25,000/mm3 PegIFN alfa-2a: discontinue until resolution
54. HOW TO MANAGE ANEMIA IN
CLINICAL PRACTICE ?
Full blood count at week 2
Hb >11 Hb <10
Check in 2 weeks
Reduce dose of
RBV
And check weekly
If Hb>10
follow up every 2 w Accurate evaluation of
the patient (age, heart
problems, SVR?
55. HOW TO MANAGE NEUTROPENIA
IN CLINICAL PRACTICE ?
Full blood count at week 2
Neutrophils >750 mm3 Neutrophils <750 mm3
Reduce dose and check
Check in 2 weekly
weeks
If N between 750 and If N still < 750 give
If N >750 follow-up 1000 Continue same dose for 2 w
every 2 weeks If N > 1000 go back With weekly check
If N >750 increase dose
to initial dose
and check weekly
56. Granulocyte colony-stimulating
factor ( G-CSF): FILGRASTIM ,
LENOGRASTIM,PEGFILGRASTIM
300 µg SC TIW Cost: 183,26 Euro
Should not be given as primary
therapy to prevent pegIFN alfa dose
reductions
57. Maintaining Patients on HCV Treatment: Strategies for Successful Retreatment
Phase II Study: Eltrombopag Increased
Platelet Counts at All Doses Evaluated
Significantly more patients with HCV-associated
thrombocytopenia achieved ≥ 100,000 cells/μL at Week 4 by
LOCF analysis in all eltrombopag dose groups compared with
placebo (P ≤ .001)
Median Platelet Count, x 103/µL (Range)
Treatment Week Eltrombopag Eltrombopag Eltrombopag
Placebo
30 mg/day 50 mg/day 75 mg/day
Baseline, N = 74 55 (27-75) 59 (34-94) 52 (26-66) 54 (28-75)
Week 4 53 (34-74) 137 (40-528) 214 (47-499) 209 (78-527)
Best responses with eltrombopag 75 mg/day
– 91% of this group able to initiate HCV therapy
– 65% of this group able to complete 12 weeks of therapy
McHutchison JG, et al. N Engl J Med. 2007;357:2227-2236. clinicaloptions.com/hep
58. Maintaining Patients on HCV Treatment: Strategies for Successful Retreatment
Hematologic AEs Associated With HCV
Therapy
Anemia Neutropenia Thrombocytopenia
Definition Hemoglobin < 12 g/dL Absolute neutrophil count Platelets < 75,000/mL
> 3 g/dL decrease in Hb < 750 cells/mL
Etiology RBV: hemolysis Interferon: bone marrow Interferon: bone marrow
IFN: bone marrow suppression suppression
suppression
Monitor Monitor labs closely first Monitor labs closely first Monitor platelet counts closely
weeks weeks during the first weeks
Assess severity of symptoms Assess severity of symptoms Assess for gum bleeding,
bruising, nose bleeds
Dose Adjust Adjust ribavirin dose Adjust interferon dose Adjust interferon dose
Consider Epoetin alfa 40,000 units SC Granulocyte colony-stimulating Administration of oprelvekin is
Pharmacologic weekly or darbepoetin alfa 3 factor 300 µg SC TIW associated with edema in the
Intervention* µgKg SC every other week Should not be given as lower extremities and cannot
primary therapy to prevent be recommended
pegIFN alfa dose reductions Phase II studies of 75 mg/day
eltrombopag shows promise
*Off-label use.
PEG-Intron [package insert]. Kenilworth, NJ: Schering Corp; March 2008. Pegasys [package insert].
Nutley, NJ: Roche Pharmaceuticals; January 2008. Soza A, et al. Hepatology. 2002;36:
1273-1279. McHutchison JG, et al. N Engl J Med. 2007;357:2227-2236. clinicaloptions.com/hep
59. Maintaining Patients on HCV Treatment: Strategies for Successful Retreatment
Hematologic AEs Associated With HCV
Therapy
Anemia Neutropenia Thrombocytopenia
Definition Hemoglobin < 12 g/dL Absolute neutrophil count Platelets < 75,000/mL
> 3 g/dL decrease in Hb < 750 cells/mL
Etiology RBV: hemolysis Interferon: bone marrow Interferon: bone marrow
IFN: bone marrow suppression suppression
suppression
Monitor Monitor labs closely first Monitor labs closely first Monitor platelet counts closely
weeks weeks during the first weeks
Assess severity of symptoms Assess severity of symptoms Assess for gum bleeding,
bruising, nose bleeds
Dose Adjust Adjust ribavirin dose Adjust interferon dose Adjust interferon dose
Consider Epoetin alfa 40,000 units SC Granulocyte colony-stimulating Administration of oprelvekin is
Pharmacologic weekly or darbepoetin alfa 3 factor 300 µg SC TIW associated with edema in the
Intervention* µgKg SC every other week Should not be given as lower extremities and cannot
primary therapy to prevent be recommended
pegIFN alfa dose reductions Phase II studies of 75 mg/day
eltrombopag shows promise
*Off-label use.
PEG-Intron [package insert]. Kenilworth, NJ: Schering Corp; March 2008. Pegasys [package insert].
Nutley, NJ: Roche Pharmaceuticals; January 2008. Soza A, et al. Hepatology. 2002;36:
1273-1279. McHutchison JG, et al. N Engl J Med. 2007;357:2227-2236. clinicaloptions.com/hep
60. Virological Response: NEW definitions
Rapid virological response
HCV-RNA undetectable at week 4
SHORTER IFN/RIBA REGIMEN (?)
Early virological response
HCV-RNA undetectable at week 12
12 WEEKS RULE FOR STOPPING THERAPY
62. Importance of Highly Sensitive HCV-RNA
Assays for IFN-treatment:
48 vs. 72 Weeks of Treatment
W 12: < 2 log HCV RNA Reduction
W 24: 24% HCV RNA negative (< 50
IU/ml)
48 Weeks of Therapy 72 Weeks of Therapy
Relapse: 87% Relapse: 46%
Berg et al. Gastroenterology 2006
63. SUSTAINED VIROLOGICAL RESPONSE
** Manns * Fried * Hadzyiannis * DITTO
• ALL
NON RESPONDERS
54% 56% 63% 66%
~45%
• Gen 1 42% 46% 52% 60%
AF ALL TREATED
• G1 HVL 30% 41% 47%
PATIENTS
• >800.000 UI/ml
HVL 42% 53% 66%
*Pegasys 180 mcg + 1000-1200 mg x 48 weeks
**Pegintron 1.5 mcg/Kg + 800 mg x 48 weeks
64. Why does HCV treatment fail?
Host factors Virus
• Race ? • Genotype
• Age • Viral load
(patient/infection)
• Gender
• High estrogens
levels Reasons for
• Body weight treatment failure
• Fibrosis
• Siderosis
• Steatosis
• Diabetes
• Active drug abuse
• Concomitant Treatment
disease • Poor adherence to therapy
• COINFECTIONS • Discontinuation for side effects
• ALCOHOL • Use of a less than effective regimen (dose/duration)
Editor's Notes
Slide . Projection of Lifetime Outcomes in HCV Infection Efforts to portray the natural history of HCV infection are complicated by a number of factors, including the asymptomatic nature of the early disease process and the lack of awareness among the general population, especially in less developed nations. This slide depicts the natural history of HCV infection as proposed by Alter and Seeff in a review of long-term outcomes data. This projection of the lifetime outcomes in HCV infection is based on a composite of available data and the most accurate estimates of the frequency of events that enhance liver disease progression. Alter and Seeff have incorporated data from retrospective, prospective, and cohort studies in their examination of the outcomes in HCV infection. Alter HF, Seeff LB. Semin Liver Dis. 2000;20:17 – 35.
Più frequenti criteri di esclusione adottai nei tials Petrtanto tutte le persone con tali criteri di esclusione non sono studiati nei trials E sulle persone con tali carrateristiche later funziona, funzionerebbe, funzionerà????
Goals of Therapy Clinically relevant goals for treatment of HCV are classified as primary or secondary. The primary goal is the eradication of the virus as evidenced by negative HCV RNA. The secondary goals include the histologic improvement of hepatic inflammation and fibrosis as evidenced by delayed fibrosis and progression to cirrhosis and prevention of hepatic decompensation and HCC. Reference Lindsay KL. Introduction to therapy of hepatitis C. Hepatology . 2002;36:S114-S120.
New Definitions of Early Virologic Response to Antiviral Therapy for Hepatitis C Patients who achieve an Early Virologic Response (EVR) can be further categorized as achieving a complete EVR (cEVR) or partial EVR (pEVR). Patients who achieve pEVR (detectable but ≥ 2 log 10 drop in HCV RNA at week 12), can be categorized as slow responders or partial responders. Slow responders are those patients who have ≥ 2 log 10 drop in HCV RNA at week 12 and are HCV RNA negative at week 24. Partial responders, on the other hand, remain HCV RNA positive at week 24. References Marcellin P, Jensen DM, Hadziyannis SJ, Ferenci P. Differentiation of early virologic response (EVR) into RVR, complete EVR (cEVR) and partial EVR (pEVR) allows for a more precise prediction of SVR in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (Pegasys) and ribavirin (Copegus). Presented at AASLD 2007. Oct. 2-6, 2007; Boston, MA. Poster #1308. Sánchez-Tapias JM, Ferenci P, Diago M, et al. How can we identify HCV genotype 1 patients who may benefit from an extended treatment duration with peginterferon alfa-2a (40KD) (Pegasys) plus ribavirin (Copegus)? Presented at EASL 2007. April 11-15, 2007; Barcelona, Spain. Poster #641. M10, S04
Slide . Quantitative HCV tests: dynamic ranges Results of viral load tests can be expressed in terms of copies per mL (which are not interchangeable between assays), and international units (IU) per mL (which can be used to make direct comparisons among assays). Assays to detect anti-HCV in patients on antiviral therapy include the COBAS AMPLICOR™ HCV MONITOR Test, v2.0 , a quantitative test used to determine the concentration of HCV RNA with a range of detection from 600 IU/mL to 500 000 IU/mL, and the AMPLICOR HCV MONITOR ® Test, v2.0 with a range of detection from 600 IU/mL to 850 000 IU/mL. 1 These tests have a qualitative lower limit of detection of approximately 50 IU/mL. 2 The COBAS TaqMan™ HCV Test has a lower limit of detection of 30 IU/mL and an upper limit of 200 million IU/mL. Another quantitative assay for monitoring viral concentrations of HCV is SuperQuant™, which has a quantitative range of 100 copies/mL to 100 million copies/mL of HCV RNA. 3 The Bayer Versant HCV RNA 3.0 Quantitation by bDNA (branched-chain DNA) assay has a quantitative range of 615 IU/mL to 7.7 million IU/mL. The Bayer Versant transcription mediated amplification (TMA) viral load test is a qualitative HCV assay that uses molecular diagnostics technology called TMA to detect the presence of HCV RNA. Its lower limit of detection is less than 50 IU/mL. 4 1. Roche Molecular Diagnostics. 2. Strader D, et al. Hepatology 2004; 39: 1147 3. National Genetics Institute. SuperQuant™ 4. Pawlotsky, J-M. Hepatology 2002; 36: S65
RVR Important Predictor of SVR: Results SVR rates were similar across genotypes in patients achieving an RVR. Multiple logistic regression analysis confirmed that RVR predicted SVR. In patients with an RVR, genotype was not a significant predictor of SVR. Reference Fried MW, Hadziyannis SJ, Shiffman M, Messinger D, Zeuzem S. Rapid virological response is a more important predictor of sustained virological response (SVR) than genotype in patients with chronic hepatitis C virus infection. Presented at EASL 2008. April 23-27, 2008; Milan, Italy. Abstract #7. F22
Predictors of Week 12 Response and SVR by Magnitude of Response at Week 4: Methods This retrospective analysis of 2 phase III studies in HCV genotype 1 patients treated with Pegasys plus RBV sought to determine whether magnitude of response at 4 weeks predicts response at 12 weeks and SVR in patients who do not achieve rapid virologic response. References Marcellin P, Reau N, Ferenci P, Jensen DM. Refined prediction of week 12 response and SVR based on the virological response at week 4 in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS). Presented at AASLD 2008. Nov 1-4, 2008; San Francisco, CA. Poster #1853. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med . 2002;347(13):975-982. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon alfa-2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140(5):346-355. F25, H01, M14
Virologic Response Rates in G1 Patients With and Without an RVR A total of 90 patients (16%) had an RVR at week 4. When grouped according to RVR status (RVR vs no RVR) patients without an RVR were much less likely to be HCV RNA negative at week 12 and to attain SVR. Reference Marcellin P, Reau N, Ferenci P, Jensen DM. Refined prediction of week 12 response and SVR based on the virological response at week 4 in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS). Presented at AASLD 2008. Nov 1-4, 2008; San Francisco, CA. Poster #1853. M14
Predictors of Week 12 Response and SVR by Magnitude of Response at Week 4: Methods This retrospective analysis of 2 phase III studies in HCV genotype 1 patients treated with Pegasys plus RBV sought to determine whether magnitude of response at 4 weeks predicts response at 12 weeks and SVR in patients who do not achieve rapid virologic response. References Marcellin P, Reau N, Ferenci P, Jensen DM. Refined prediction of week 12 response and SVR based on the virological response at week 4 in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS). Presented at AASLD 2008. Nov 1-4, 2008; San Francisco, CA. Poster #1853. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med . 2002;347(13):975-982. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon alfa-2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140(5):346-355. F25, H01, M14
Virologic Response Rates at Weeks 12 and 72 in Genotype 1 Patients When patients without RVR were subdivided according to the magnitude of reduction in HCV RNA levels between baseline and week 4, probability of SVR correlated with degree of response at week 4, with the highest likelihood of SVR occurring in those with unquantifiable (77%) or > 3 log 10 drop (61%) at week 4. There was a similar trend in the proportion of patients within each subgroup who were HCV RNA-negative at week 12. Reference Marcellin P, Reau N, Ferenci P, Jensen DM. Refined prediction of week 12 response and SVR based on the virological response at week 4 in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS). Presented at AASLD 2008. Nov 1-4, 2008; San Francisco, CA. Poster #1853. M14
Predictors of Week 12 Response and SVR by Magnitude of Response at Week 4: Conclusions Rapid virologic response is a good predictor of SVR in patients treated with peginterferon alfa-2a and ribavirin. Even in patients without RVR, degree of decline in HCV RNA levels between baseline and week 4 can be useful in predicting SVR. Unquantifiable ( ≥ 50, but < 600 IU/mL) HCV RNA or > 3 log 10 drop in HCV RNA levels are highly predictive of SVR. Reference Marcellin P, Reau N, Ferenci P, Jensen DM. Refined prediction of week 12 response and SVR based on the virological response at week 4 in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS). Presented at AASLD 2008. Nov 1-4, 2008; San Francisco, CA. Poster #1853. M14
Patients With a Durable SVR at Mean 4.1 (0.4 – 7) Years Follow-up The vast majority of patients who achieved an SVR had a durable response at a mean follow-up of 4 years irrespective of their disease status or treatment regimen. Reference Swain M, Lai MY, Shiffman ML, et al. Durable sustained virological response (SVR) after treatment with peginterferon alfa-2a (40KD) (Pegasys) alone or in combination with ribavirin (Copegus): 5-year follow-up and the criteria of a cure. Presented at EASL 2007. April 11-15, 2007; Barcelona, Spain. Abstract #1. S52
LOCF, last observation carry-forward. The results showed that there was no change in platelet levels at Week 4 compared with baseline levels in placebo patients; however, for patients who received 30 mg/day, 50 mg/day, or 75 mg/day eltrombopag, there was a significant increase in platelet counts up to levels that enabled the majority of patients to complete HCV treatment.
AEs, adverse events; Hb, hemoglobin; IFN, interferon; pegIFN, peginterferon; PI, package insert; RBV, ribavirin; SC, subcutaneous; TIW, 3 times each week. This slide lists some of the definitions related to hematologic adverse events as outlined in package inserts. In dealing with these events, growth factors are not used very often, with approximately 5% to 10% of patients receiving erythropoietin, and even fewer receiving filgrastim
AEs, adverse events; Hb, hemoglobin; IFN, interferon; pegIFN, peginterferon; PI, package insert; RBV, ribavirin; SC, subcutaneous; TIW, 3 times each week. This slide lists some of the definitions related to hematologic adverse events as outlined in package inserts. In dealing with these events, growth factors are not used very often, with approximately 5% to 10% of patients receiving erythropoietin, and even fewer receiving filgrastim
Slide . Quantitative HCV tests: dynamic ranges Results of viral load tests can be expressed in terms of copies per mL (which are not interchangeable between assays), and international units (IU) per mL (which can be used to make direct comparisons among assays). Assays to detect anti-HCV in patients on antiviral therapy include the COBAS AMPLICOR™ HCV MONITOR Test, v2.0 , a quantitative test used to determine the concentration of HCV RNA with a range of detection from 600 IU/mL to 500 000 IU/mL, and the AMPLICOR HCV MONITOR ® Test, v2.0 with a range of detection from 600 IU/mL to 850 000 IU/mL. 1 These tests have a qualitative lower limit of detection of approximately 50 IU/mL. 2 The COBAS TaqMan ™ HCV Test has a lower limit of detection of 30 IU/mL and an upper limit of 200 million IU/mL. Another quantitative assay for monitoring viral concentrations of HCV is SuperQuant™, which has a quantitative range of 100 copies/mL to 100 million copies/mL of HCV RNA. 3 The Bayer Versant HCV RNA 3.0 Quantitation by bDNA (branched-chain DNA) assay has a quantitative range of 615 IU/mL to 7.7 million IU/mL. The Bayer Versant transcription mediated amplification (TMA) viral load test is a qualitative HCV assay that uses molecular diagnostics technology called TMA to detect the presence of HCV RNA. Its lower limit of detection is less than 50 IU/mL. 4 1. Roche Molecular Diagnostics. 2. Strader D, et al. Hepatology 2004; 39: 1147 3. National Genetics Institute. SuperQuant™ 4. Pawlotsky, J-M. Hepatology 2002; 36: S65