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
Hepatotoxicity, or liver toxicity, can result from anti-tuberculosis (TB) drugs and is known as drug-induced hepatitis (DIH). Patients at high risk include those with pre-existing liver conditions, alcohol use, and advanced TB. Monitoring of liver enzymes is important for high risk patients during TB treatment. Symptoms of DIH include fatigue, nausea, and jaundice. Diagnosis involves abnormal liver enzymes and symptom resolution after stopping anti-TB drugs. Management consists of gradual dose escalation while monitoring for toxicity.
Toxic hepatitis can be caused by alcohol, drugs, chemicals or supplements. Acetaminophen is a common cause when taken in high doses, as it is metabolized to a toxic metabolite that depletes glutathione stores. Diagnosis involves a history of exposures, physical exam noting jaundice potentially, and liver function tests showing elevated ALT and bilirubin. Treatment focuses on stopping the toxin and using N-acetylcysteine for acetaminophen toxicity to replenish glutathione within 8-24 hours of overdose. Prevention requires limiting intake, not exceeding medication directions, avoiding alcohol with medications, and following dosage guidelines.
This document summarizes drug-induced liver injury (DILI). It notes that DILI occurs in 1 in 10,000 to 100,000 people and can cause significant morbidity and mortality. The document outlines various risk factors for DILI, including female sex, age, nutritional status, preexisting liver disease, and concomitant drug usage. It also describes the clinical spectrum of DILI, from elevated liver enzymes to fulminant hepatic failure, and specific types of injury like acute hepatocellular, cholestatic, and mixed injury patterns.
Hepatotoxicity is chemically-driven liver damage caused by drugs or other exposures. The liver plays an important role in metabolizing chemicals and is susceptible to toxicity from overdoses of certain agents or even therapeutic levels sometimes. Hepatotoxicity can be classified as intrinsic or idiosyncratic, with the latter divided into allergic and non-allergic types. The liver is vulnerable to injury from substances due to its unique metabolism and blood flow from the GI tract. Damage to liver cells can release oxidative compounds and disrupt mitochondria, further harming the liver. Common symptoms include jaundice, fatigue, nausea and dark urine. Acetaminophen overdose is a major cause of acute liver failure and often
Hepatotoxicity can be caused by carbon tetrachloride, acetaminophen, ethanol, and aflatoxins. Carbon tetrachloride and aflatoxins cause liver damage through toxic free radicals produced during metabolism. Acetaminophen overwhelms the liver's glutathione reserves, producing a toxic metabolite. Ethanol induces cytochrome P450 enzymes that produce toxic radicals, depleting glutathione and causing lipid peroxidation and cell damage. Clinical signs include nausea, vomiting, mental status changes, and liver failure. Treatment focuses on supportive care, activated charcoal or N-acetylcysteine to prevent further toxicity. There are no antidotes for aflatoxins.
Drugs are a major cause of liver injury, accounting for 20-40% of instances. Certain groups are at higher risk, such as those with preexisting liver disease, genetic factors affecting drug metabolism, or who consume alcohol. Drugs can cause liver injury through various mechanisms, including disrupting hepatocytes, bile ducts, or mitochondrial function. Clinical manifestations range from asymptomatic elevated enzymes to fulminant hepatic failure.
This document discusses hepatotoxicity and liver injury. It covers clinical chemistry markers of liver injury including ALT, SDH, ALP, total bile acids, and bilirubin. It provides examples of clinical chemistry profiles that could indicate hepatocellular injury, cholestasis, or biliary obstruction. Organ weights and histopathological assessments are also important for evaluating hepatotoxicity. The liver has complex cellular architecture and various cell types can be involved in injury responses.
Hepatotoxicity, or liver toxicity, can result from anti-tuberculosis (TB) drugs and is known as drug-induced hepatitis (DIH). Patients at high risk include those with pre-existing liver conditions, alcohol use, and advanced TB. Monitoring of liver enzymes is important for high risk patients during TB treatment. Symptoms of DIH include fatigue, nausea, and jaundice. Diagnosis involves abnormal liver enzymes and symptom resolution after stopping anti-TB drugs. Management consists of gradual dose escalation while monitoring for toxicity.
Toxic hepatitis can be caused by alcohol, drugs, chemicals or supplements. Acetaminophen is a common cause when taken in high doses, as it is metabolized to a toxic metabolite that depletes glutathione stores. Diagnosis involves a history of exposures, physical exam noting jaundice potentially, and liver function tests showing elevated ALT and bilirubin. Treatment focuses on stopping the toxin and using N-acetylcysteine for acetaminophen toxicity to replenish glutathione within 8-24 hours of overdose. Prevention requires limiting intake, not exceeding medication directions, avoiding alcohol with medications, and following dosage guidelines.
This document summarizes drug-induced liver injury (DILI). It notes that DILI occurs in 1 in 10,000 to 100,000 people and can cause significant morbidity and mortality. The document outlines various risk factors for DILI, including female sex, age, nutritional status, preexisting liver disease, and concomitant drug usage. It also describes the clinical spectrum of DILI, from elevated liver enzymes to fulminant hepatic failure, and specific types of injury like acute hepatocellular, cholestatic, and mixed injury patterns.
Hepatotoxicity is chemically-driven liver damage caused by drugs or other exposures. The liver plays an important role in metabolizing chemicals and is susceptible to toxicity from overdoses of certain agents or even therapeutic levels sometimes. Hepatotoxicity can be classified as intrinsic or idiosyncratic, with the latter divided into allergic and non-allergic types. The liver is vulnerable to injury from substances due to its unique metabolism and blood flow from the GI tract. Damage to liver cells can release oxidative compounds and disrupt mitochondria, further harming the liver. Common symptoms include jaundice, fatigue, nausea and dark urine. Acetaminophen overdose is a major cause of acute liver failure and often
Hepatotoxicity can be caused by carbon tetrachloride, acetaminophen, ethanol, and aflatoxins. Carbon tetrachloride and aflatoxins cause liver damage through toxic free radicals produced during metabolism. Acetaminophen overwhelms the liver's glutathione reserves, producing a toxic metabolite. Ethanol induces cytochrome P450 enzymes that produce toxic radicals, depleting glutathione and causing lipid peroxidation and cell damage. Clinical signs include nausea, vomiting, mental status changes, and liver failure. Treatment focuses on supportive care, activated charcoal or N-acetylcysteine to prevent further toxicity. There are no antidotes for aflatoxins.
Drugs are a major cause of liver injury, accounting for 20-40% of instances. Certain groups are at higher risk, such as those with preexisting liver disease, genetic factors affecting drug metabolism, or who consume alcohol. Drugs can cause liver injury through various mechanisms, including disrupting hepatocytes, bile ducts, or mitochondrial function. Clinical manifestations range from asymptomatic elevated enzymes to fulminant hepatic failure.
This document discusses hepatotoxicity and liver injury. It covers clinical chemistry markers of liver injury including ALT, SDH, ALP, total bile acids, and bilirubin. It provides examples of clinical chemistry profiles that could indicate hepatocellular injury, cholestasis, or biliary obstruction. Organ weights and histopathological assessments are also important for evaluating hepatotoxicity. The liver has complex cellular architecture and various cell types can be involved in injury responses.
The document discusses hepatotoxicity or liver damage. It begins by explaining the liver's role in detoxification and how certain toxins can damage the liver. It then describes the location of the liver and several mechanisms by which chemicals can injure liver cells. Common signs of liver damage include jaundice, fatigue and nausea. Many drugs, toxins, infections and other agents are identified that can cause liver damage through different pathological forms. Treatment focuses on removing the toxic agent and providing supportive care, with transplants as a last resort for severe liver failure.
The document discusses hepatotoxicity, or liver injury caused by chemicals. The liver is the primary site of drug metabolism and many drugs can cause liver damage. Hepatotoxicity can be direct, through overdose, or idiosyncratic, through hypersensitivity reactions. Liver function tests are used to detect abnormalities and extent of damage. Several drugs are described that can cause hepatotoxicity through different mechanisms, such as paracetamol causing centrizonal necrosis, isoniazid causing multilobular necrosis, and halothane causing an immune response through metabolite binding. Regular monitoring of liver enzymes is recommended when taking hepatotoxic drugs.
The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms.
Alcohol consumption can lead to various liver diseases known as alcoholic liver disease (ALD). Chronic heavy drinking is responsible for 50% of chronic liver disease cases in India. Symptoms of ALD may not appear until the disease is advanced and include fatigue, abdominal swelling and pain, and jaundice. Alcohol is metabolized in the liver, producing reactive oxygen species that can cause oxidative stress, fatty liver, inflammation, fibrosis and eventually cirrhosis over many years. Diagnosis involves assessing drinking history, symptoms, lab tests and biopsy. Treatment focuses on abstaining from alcohol. Corticosteroids and antioxidants may help in some cases. Liver transplantation is an option for end-stage ALD but is not usually recommended for
This document provides information on various types of lipoproteins:
- It defines lipoproteins as biochemical assemblies containing both lipids and proteins that allow fats to move through water.
- It classifies lipoproteins based on density, electrophoretic mobility, and apolipoprotein content into chylomicrons, VLDL, IDL, LDL, and HDL.
- It describes the structure of lipoproteins consisting of a nonpolar lipid core surrounded by a surface layer of amphipathic lipids and proteins.
- It details the functions and metabolism of various lipoproteins including their role in transporting lipids between tissues and organs.
The document summarizes the different types of liver injury and conditions that can result from toxic effects on the liver. It discusses how chemicals can cause hepatocellular degeneration through damaging mitochondria, plasma membranes, the endoplasmic reticulum, or nucleus of liver cells. This can lead to fibrosis, cirrhosis, or liver tumors over time. Other toxic effects include cholestasis (decreased bile flow), sinusoidal damage, peliosis hepatis (blood-filled cysts), and fatty liver caused by lipid accumulation within liver cells. The document provides examples of chemicals that can induce each type of toxic liver effect.
Cardiotoxicity refers to heart damage caused by certain chemotherapy drugs, heavy metals, and other toxins. Three main mechanisms of cardiotoxicity are discussed: interfering with aerobic metabolism in the heart, altering myocardial conduction, and directly damaging heart muscle cells. Symptoms of cardiotoxicity include fatigue, shortness of breath, and swelling. Diagnosis involves physical exams, imaging tests like echocardiograms and MUGA scans, and blood tests. Prevention strategies center around modifying drug treatment plans, using protective medications like dexrazoxane, and controlling risk factors after treatment through medications like ACE inhibitors and beta-blockers.
in this presentation, the light is focused on discussing the Reactive oxygen species, oxidative stress, how it forms, how it affects the body and what are the diseases that correlate with oxidative stress.
nevertheless, how it can be balanced by the antioxidants and what is their role in oxidative stress.
Tetrodotoxin is a potent neurotoxin found in marine animals like pufferfish. It blocks sodium channels, preventing action potentials and paralyzing neurons and muscles. Poisoning symptoms range from numbness to respiratory failure and death. The toxin is produced by various bacteria in marine life. While rare, poisoning is more common where pufferfish is regularly consumed. There is no antidote, so treatment focuses on supportive care and monitoring until the toxin is cleared from the body.
This document provides an outline and objectives for a nursing assignment on the assessment and management of patients with hepatic disorders. It covers topics such as the anatomy and physiology of the liver, causes of liver disease, signs and symptoms of hepatic dysfunction including jaundice, portal hypertension and ascites. It also discusses management of conditions like hepatic encephalopathy, bleeding esophageal varices, hepatitis, cirrhosis and cancer of the liver. Nursing interventions are focused on activity tolerance, nutrition, skin integrity and preventing complications.
Free radicals in human diseases and the roleMohammed Sakr
Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Free radicals are a main cause of cardiovascular diseases, cancer, aging and immune defense disorders. Foods like berries and carrot protect us against free radicals.
Just regarded to those who trying to learn somethings.. . thanks to those who read this slide... Just pray for me , for my parents and for my teachers...
Oxidative stress occurs due to an imbalance between free radicals and antioxidants in the body. Free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS) can be generated endogenously through normal metabolism or exogenously through environmental exposures. They damage cells and tissues through lipid peroxidation and reactions with DNA, proteins, and other molecules. Antioxidants help reduce oxidative stress by scavenging or preventing the formation of free radicals. Common antioxidants include enzymes like superoxide dismutase, catalase, and glutathione peroxidase as well as vitamins C and E. However, antioxidants can also act as pro-oxidants in high amounts or conditions of high oxygen pressure.
This seminar discusses oxygen free radicals and their scavengers. It defines free radicals as atoms or groups of atoms with unpaired electrons that are highly reactive. The body produces free radicals during normal processes like energy production, but they can also be generated by external factors like pollution and smoking. Free radicals can damage cells by stealing electrons from nearby molecules and initiating chain reactions. The body has antioxidant defenses against free radicals like superoxide dismutase, glutathione, and catalase that neutralize them. However, excessive free radical production or insufficient antioxidants can lead to oxidative stress and cell/tissue damage implicated in diseases.
The document discusses various aspects of detoxification including:
1. Detoxification is the process by which toxic substances are rendered less harmful and more water soluble through biochemical transformations in the body.
2. Xenobiotics are compounds that are foreign to the body which can be ingested through foods, drugs, or produced endogenously.
3. Biotransformation is the process by which substances are chemically changed in the body, either activating or inactivating them, through phase 1 and phase 2 reactions like oxidation, reduction, and conjugation.
This document discusses a lecture on hypercholesterolemia and atherosclerosis. It begins with learning objectives about understanding the pathobiology and risk factors of hypercholesterolemia and atherosclerosis. It then defines hyperlipidemia and its causes, describing how elevated LDL-C promotes cardiovascular disease. The document discusses the classification, indications, mechanisms and adverse effects of drug treatments for hyperlipidemia, focusing on statins, bile acid sequestrants, ezetimibe, fibrates and omega-3 fatty acids.
This document discusses hepatotoxicity (liver toxicity or damage). It begins by describing the liver's important roles and how an imbalance between protective and aggressive forces can lead to hepatotoxicity from environmental and chemical agents. Common mechanisms of hepatotoxicity include inflammation, immunomodulation, and oxidative stress. Several drugs are described as potential causes of hepatotoxicity, including acetaminophen, carbontetrachloride, ethanol, and some antitubercular drugs. Signs and symptoms of hepatotoxicity and treatments such as supportive care or liver transplant are also summarized. A case study describes hepatotoxicity resulting from antitubercular therapy.
This document discusses drug-induced liver injury (DILI). It begins by stating that multiple drugs can cause hepatotoxicity through various mechanisms. It then discusses the epidemiology of DILI, noting that its worldwide annual incidence is estimated between 1.3 to 19.1 per 100,000 exposed individuals. The document outlines the pathogenesis, clinical presentation, diagnosis, classification, histology, and management of DILI. Regarding histology, it describes various patterns of injury that can be seen such as hepatocellular necrosis, cholestasis, steatosis, and sinusoidal obstruction syndrome. The primary treatment for DILI is withdrawal of the causative drug, with specific therapies for certain cases like
The document discusses hepatotoxicity or liver damage. It begins by explaining the liver's role in detoxification and how certain toxins can damage the liver. It then describes the location of the liver and several mechanisms by which chemicals can injure liver cells. Common signs of liver damage include jaundice, fatigue and nausea. Many drugs, toxins, infections and other agents are identified that can cause liver damage through different pathological forms. Treatment focuses on removing the toxic agent and providing supportive care, with transplants as a last resort for severe liver failure.
The document discusses hepatotoxicity, or liver injury caused by chemicals. The liver is the primary site of drug metabolism and many drugs can cause liver damage. Hepatotoxicity can be direct, through overdose, or idiosyncratic, through hypersensitivity reactions. Liver function tests are used to detect abnormalities and extent of damage. Several drugs are described that can cause hepatotoxicity through different mechanisms, such as paracetamol causing centrizonal necrosis, isoniazid causing multilobular necrosis, and halothane causing an immune response through metabolite binding. Regular monitoring of liver enzymes is recommended when taking hepatotoxic drugs.
The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms.
Alcohol consumption can lead to various liver diseases known as alcoholic liver disease (ALD). Chronic heavy drinking is responsible for 50% of chronic liver disease cases in India. Symptoms of ALD may not appear until the disease is advanced and include fatigue, abdominal swelling and pain, and jaundice. Alcohol is metabolized in the liver, producing reactive oxygen species that can cause oxidative stress, fatty liver, inflammation, fibrosis and eventually cirrhosis over many years. Diagnosis involves assessing drinking history, symptoms, lab tests and biopsy. Treatment focuses on abstaining from alcohol. Corticosteroids and antioxidants may help in some cases. Liver transplantation is an option for end-stage ALD but is not usually recommended for
This document provides information on various types of lipoproteins:
- It defines lipoproteins as biochemical assemblies containing both lipids and proteins that allow fats to move through water.
- It classifies lipoproteins based on density, electrophoretic mobility, and apolipoprotein content into chylomicrons, VLDL, IDL, LDL, and HDL.
- It describes the structure of lipoproteins consisting of a nonpolar lipid core surrounded by a surface layer of amphipathic lipids and proteins.
- It details the functions and metabolism of various lipoproteins including their role in transporting lipids between tissues and organs.
The document summarizes the different types of liver injury and conditions that can result from toxic effects on the liver. It discusses how chemicals can cause hepatocellular degeneration through damaging mitochondria, plasma membranes, the endoplasmic reticulum, or nucleus of liver cells. This can lead to fibrosis, cirrhosis, or liver tumors over time. Other toxic effects include cholestasis (decreased bile flow), sinusoidal damage, peliosis hepatis (blood-filled cysts), and fatty liver caused by lipid accumulation within liver cells. The document provides examples of chemicals that can induce each type of toxic liver effect.
Cardiotoxicity refers to heart damage caused by certain chemotherapy drugs, heavy metals, and other toxins. Three main mechanisms of cardiotoxicity are discussed: interfering with aerobic metabolism in the heart, altering myocardial conduction, and directly damaging heart muscle cells. Symptoms of cardiotoxicity include fatigue, shortness of breath, and swelling. Diagnosis involves physical exams, imaging tests like echocardiograms and MUGA scans, and blood tests. Prevention strategies center around modifying drug treatment plans, using protective medications like dexrazoxane, and controlling risk factors after treatment through medications like ACE inhibitors and beta-blockers.
in this presentation, the light is focused on discussing the Reactive oxygen species, oxidative stress, how it forms, how it affects the body and what are the diseases that correlate with oxidative stress.
nevertheless, how it can be balanced by the antioxidants and what is their role in oxidative stress.
Tetrodotoxin is a potent neurotoxin found in marine animals like pufferfish. It blocks sodium channels, preventing action potentials and paralyzing neurons and muscles. Poisoning symptoms range from numbness to respiratory failure and death. The toxin is produced by various bacteria in marine life. While rare, poisoning is more common where pufferfish is regularly consumed. There is no antidote, so treatment focuses on supportive care and monitoring until the toxin is cleared from the body.
This document provides an outline and objectives for a nursing assignment on the assessment and management of patients with hepatic disorders. It covers topics such as the anatomy and physiology of the liver, causes of liver disease, signs and symptoms of hepatic dysfunction including jaundice, portal hypertension and ascites. It also discusses management of conditions like hepatic encephalopathy, bleeding esophageal varices, hepatitis, cirrhosis and cancer of the liver. Nursing interventions are focused on activity tolerance, nutrition, skin integrity and preventing complications.
Free radicals in human diseases and the roleMohammed Sakr
Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Free radicals are a main cause of cardiovascular diseases, cancer, aging and immune defense disorders. Foods like berries and carrot protect us against free radicals.
Just regarded to those who trying to learn somethings.. . thanks to those who read this slide... Just pray for me , for my parents and for my teachers...
Oxidative stress occurs due to an imbalance between free radicals and antioxidants in the body. Free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS) can be generated endogenously through normal metabolism or exogenously through environmental exposures. They damage cells and tissues through lipid peroxidation and reactions with DNA, proteins, and other molecules. Antioxidants help reduce oxidative stress by scavenging or preventing the formation of free radicals. Common antioxidants include enzymes like superoxide dismutase, catalase, and glutathione peroxidase as well as vitamins C and E. However, antioxidants can also act as pro-oxidants in high amounts or conditions of high oxygen pressure.
This seminar discusses oxygen free radicals and their scavengers. It defines free radicals as atoms or groups of atoms with unpaired electrons that are highly reactive. The body produces free radicals during normal processes like energy production, but they can also be generated by external factors like pollution and smoking. Free radicals can damage cells by stealing electrons from nearby molecules and initiating chain reactions. The body has antioxidant defenses against free radicals like superoxide dismutase, glutathione, and catalase that neutralize them. However, excessive free radical production or insufficient antioxidants can lead to oxidative stress and cell/tissue damage implicated in diseases.
The document discusses various aspects of detoxification including:
1. Detoxification is the process by which toxic substances are rendered less harmful and more water soluble through biochemical transformations in the body.
2. Xenobiotics are compounds that are foreign to the body which can be ingested through foods, drugs, or produced endogenously.
3. Biotransformation is the process by which substances are chemically changed in the body, either activating or inactivating them, through phase 1 and phase 2 reactions like oxidation, reduction, and conjugation.
This document discusses a lecture on hypercholesterolemia and atherosclerosis. It begins with learning objectives about understanding the pathobiology and risk factors of hypercholesterolemia and atherosclerosis. It then defines hyperlipidemia and its causes, describing how elevated LDL-C promotes cardiovascular disease. The document discusses the classification, indications, mechanisms and adverse effects of drug treatments for hyperlipidemia, focusing on statins, bile acid sequestrants, ezetimibe, fibrates and omega-3 fatty acids.
This document discusses hepatotoxicity (liver toxicity or damage). It begins by describing the liver's important roles and how an imbalance between protective and aggressive forces can lead to hepatotoxicity from environmental and chemical agents. Common mechanisms of hepatotoxicity include inflammation, immunomodulation, and oxidative stress. Several drugs are described as potential causes of hepatotoxicity, including acetaminophen, carbontetrachloride, ethanol, and some antitubercular drugs. Signs and symptoms of hepatotoxicity and treatments such as supportive care or liver transplant are also summarized. A case study describes hepatotoxicity resulting from antitubercular therapy.
This document discusses drug-induced liver injury (DILI). It begins by stating that multiple drugs can cause hepatotoxicity through various mechanisms. It then discusses the epidemiology of DILI, noting that its worldwide annual incidence is estimated between 1.3 to 19.1 per 100,000 exposed individuals. The document outlines the pathogenesis, clinical presentation, diagnosis, classification, histology, and management of DILI. Regarding histology, it describes various patterns of injury that can be seen such as hepatocellular necrosis, cholestasis, steatosis, and sinusoidal obstruction syndrome. The primary treatment for DILI is withdrawal of the causative drug, with specific therapies for certain cases like
Drug induced liver injury Dr Suresh GorkaSuresh Gorka
Drug-induced liver injury (DILI) can present in various forms from asymptomatic elevation of liver enzymes to jaundice and acute liver failure. DILI is most commonly caused by antimicrobials worldwide and antituberculosis drugs in India. The mechanisms of DILI include intrinsic toxicity, idiosyncratic reactions, mitochondrial toxicity, and defects in bile transport. Diagnosing DILI requires excluding other causes of hepatitis since it is a diagnosis of exclusion. A liver biopsy may be considered to help identify chronic DILI or autoimmune features.
Overview of Drug induced liver injury EASL 2019 guidelinesAhmed Elmoughazy
1. Drug-induced liver injury (DILI) has an incidence of 14 to 19 cases per 100,000 persons and is responsible for 3 to 5% of hospital admissions for jaundice.
2. DILI can be caused by direct hepatotoxicity from intrinsically toxic agents or idiosyncratic hepatotoxicity from agents that rarely cause injury.
3. Risk factors for DILI include old age, female sex, metabolic syndrome, and chronic hepatitis B or C. Drugs that cause DILI often have hepatic metabolism by cytochrome P450 enzymes and form reactive metabolites.
Type A and Type B adverse drug reactions can both cause liver injury. Type A reactions are intrinsic and dose-dependent, such as acetaminophen toxicity. Type B reactions are idiosyncratic and result from unpredictable factors in susceptible individuals. Risk factors for Type B reactions include medications that produce toxic metabolites, pre-existing liver disease, concomitant medications, age, and genetics. Resources like LiverTox help clinicians identify and manage drug-induced liver injury.
ACLF is acute liver failure resulting from an acute insult in a patient with chronic liver disease or cirrhosis. It can develop from reactivation of hepatitis B, hepatitis E infection, alcohol consumption, drug-induced liver injury, variceal bleeding, or bacterial infections in cirrhotic patients. ACLF severity is classified from grades 1 to 3 based on the number of organ failures. Treatment involves nutritional support, antibiotics for infections, albumin administration, and renal replacement therapy for kidney failure. Liver transplantation or artificial liver support devices may be considered for severe cases, though overall mortality remains high.
“Comparitive Study of Prevalence of Hyperlactatemia in HIV / AIDS Patients re...IOSR Journals
Hyperlactatemia is one of the important metabolic abnormalities in HIV infected patients. The
prevalence of hyperlactatemia in natural course of HIV disease is approximately about 2%. Aim of this study is
to estimate the prevalence of hyperlactatemia in HIV patients receiving two antiretroviral regimens, advocated
by NACO by monitoring the plasma lactate levels. This study was taken up with 200 patients to compare the
prevalence of hyperlactatemia of two commonly used NACO regimens (zidovudine+ lamivudine+ nevirapine)
Vs (stavudine+ lamivudine+ nevirapine). The plasma lactate levels were estimated between 9th to 18thmonth
after initiation of antiretroviral therapy. The comparision and correlation between plasma lactate levels, CD4
counts and haemoglobin percentage in both regimens was done. There was statistically significant rise in the
plasma lactate levels (p<0.05) in both regimens. The increase in plasma lactate levels is more in stavudine
group compared to zidovudine group. There was low degree of positive correlation between plasma lactate and
haemoglobin in Stavudine group but negative correlation between Plasma lactate and CD4 counts in both
groups. More focus is needed on Pharmacovigilance of NRTIs induced hyperlactatemia especially Stavudine.
This document discusses drug-induced liver injury (DILI) caused by anti-tuberculosis drugs. It notes that isoniazid, rifampicin, and pyrazinamide, which are essential first-line drugs for tuberculosis treatment, can all cause hepatotoxicity. It outlines the mechanisms of anti-TB drug toxicity including direct toxicity, idiosyncratic reactions, and enzyme induction. Risk factors for anti-TB DILI are described. Diagnosis involves criteria such as elevated liver enzymes and bilirubin levels as well as tools like the RUCAM scoring system. Management recommendations include monitoring liver function tests during treatment, criteria for stopping drugs, second-line drug regimens after stopping first
ADRs
Classifications of ADRs
Thompson and DoTS system classification
Factors: age, gender, Co-morbidities, ethnicity, Pharmacogenetics,G6PD deficiency, porphyrias
Immunological reactions
Classifications
Epidemiology and pharmacovigilance of ADRs
Yellow card scheme,
Thalidomide tragedy
Factors that may raise or suppress suspicion of a drug
Synthetic Drugs/Hormones - Boon or Bane- Concept of Dooshivisha and Gara VishaIJARIIT
21st century is the world full of synthetics and everyone are living in the influence of synthetic substances. Altered life
styles, food habits and irregular sleep pattern had resulted not only Non communicable disease but also resulting in reduced
immunity and is risking the person more for infections. Pharma Industry has grown as big as hierarchy in recent centauries
and introduces new chemical molecules quoting as capable for treating diabetes, hypertension etc. But bitter truth is prolonged
usage these medications itself has adverse effect on liver and kidneys causes hepatotoxicity and nephrotoxicity or organs
specific toxicity.
This document discusses non-alcoholic fatty liver disease (NAFLD), which ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. It occurs without significant alcohol use or other known causes. Risk factors include obesity, dyslipidemia, and type 2 diabetes. Due to the rise in metabolic syndrome, NAFLD is now the most common cause of chronic liver disease. Genetic and metabolic factors like insulin resistance and inflammation contribute to its development and progression. Liver biopsy is still the gold standard for diagnosis but carries risks, so noninvasive imaging methods are being developed and studied.
The essay discusses obesity, specifically childhood obesity, as a growing problem in the US and West Virginia. West Virginia has the 2nd highest obesity rate in the US at 35.7% as of 2014. Childhood obesity has doubled for children ages 6-11 and quadrupled for ages 12-19 in the last 30 years. The essay will examine factors contributing to West Virginia's high obesity rates.
This document provides an overview of sepsis, including its epidemiology, etiology, signs and symptoms, diagnosis, management, and complications. It begins with an introduction defining sepsis as an unbalanced immune response to infection that can damage tissues and organs. It then discusses the typical bacterial causes of sepsis and risk factors. The document presents a case report of a child treated for sepsis and concludes that sepsis can damage multiple organs and in serious cases may require advanced organ support.
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.
The liver performs many essential functions, including processing nutrients, manufacturing bile, and breaking down toxic substances. Inflammation of the liver can interfere with these processes. Drugs are a common cause of liver injury, with over 900 drugs reported to cause hepatotoxicity. Risk factors for drug-induced liver injury include both drug-related factors like dose and concomitant medications, as well as host-related factors like age, sex, preexisting liver disease, and genetic differences affecting drug metabolism. Common drugs that can damage the liver include antibiotics, antipsychotics, statins, antifungals, antihypertensives, and herbal supplements.
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.
Prof. a. el sebaeii.fluid management in patients with akiwessam1071
Acute renal failure (ARF) is common in intensive care units (ICUs) and is associated with high mortality. Early fluid management is important to prevent and treat ARF. While aggressive hydration and maintaining adequate blood pressure can help prevent ARF, both overhydration and underhydration should be avoided as they can worsen renal function. No intravenous fluid is ideal, and fluid choice and management should be tailored to the individual patient based on their fluid status and needs. Early initiation of renal replacement therapy should be considered for patients with complications from ARF such as fluid overload or electrolyte abnormalities.
This document summarizes key factors related to drug rechallenge following drug-induced liver injury (DILI). It finds that nearly 50 drugs are associated with positive rechallenge, defined as ALT levels 3-5x upper limits of normal. Drugs that cause mitochondrial impairment or immunoallergic injury in vitro have higher positive rechallenge rates, as do those with a daily dose over 50mg. Personal factors like genetics and environment also influence outcomes. Drugs associated with DILI in clinical trials tend to have higher ALT elevations than placebos. While rechallenge carries risks, it may be considered for critical medications if alternatives are unavailable and patients can be closely monitored. More data is still needed to better understand outcomes and identify re
Non Alcoholic Fatty Liver Disease: A New Urban Epidemic.KETAN VAGHOLKAR
This document discusses non-alcoholic fatty liver disease (NAFLD), which has become very common in urban populations. NAFLD ranges from simple fatty liver to non-alcoholic steatohepatitis (NASH), which is characterized by fatty changes, inflammation, and fibrosis that can progress to cirrhosis. The main causes are obesity, insulin resistance, and dyslipidemia. Weight loss and improving insulin sensitivity through diet and exercise are the primary treatment approaches. Medications like vitamin E, pioglitazone, and metformin may also provide benefits, but more research is still needed on medical therapies for NAFLD.
Similar to An Update on Drug-induced Liver Injury (20)
5. JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
Table 3 Types of idiosyncratic drug-induced liver injury (Adapted from Ref. 29).
Basis for injury Latency period Dose related Skin rashes, fever, Rechallenge Drugs
LNE, eosinophilia
Hypersensitivity 1–6 weeks No Yes No Phenytoin
Carbamazepine
Lamotrigine
Metabolic 1–52 weeks, variable Yes No Yes INH, PZA
Abbreviations: LNE: lymph node enlargement, INH: isoniazid, PZA: pyrazinamide.
Several causality assessment methods have been estab- exclusion of competing non drug causes, previous history
lished as tools in the accurate diagnosis of DILI. The earli- of the culprit drug causing hepatotoxicity, and response to
est by Naranjo et al is a generic assessment tool for adverse rechallenge.23 Each of these domains are assigned points
drug reaction (ADR) and is not limited to DILI.33 Al- ranging from À3 to +3 depending upon the probability
though simple to use, it was primarily designed for use of a drug's involvement in DILI and the final score tallied
in clinical trials, much less in clinical practise and has to yield scores between À7 and +14. The final scores are
been supplanted by others, which are more specific for graded into five categories of likelihood of disease: Highly
DILI. These include the Roussel Uclaf Causality Assess- probable; score >8, probable; score 6–8, possible; score 3–5,
ment Method (RUCAM),23 Maria and Victorino (M and unlikely; score 1–2, excluded; score <0.23 Shortcomings
V) method34 and the more recent DILIN (Drug-Induced persist in the revised RUCAM scoring system lending itself
Liver Injury Network) expert opinion.35 The DILIN expert to a degree of subjectivity and ambiguity. Points allocated
opinion scale although has a better predictive value is lim- for rechallenge, age criteria and multiple drugs are some of
ited by the need for a group of experts for validation and the shortcomings.
hence difficult in a hospital settings or in solo practise. Maria and Victorino scale (M and V scale) was devised as
When RUCAM was compared with M and V method, RU- an alternative to RUCAM.34 Also called the Clinical Diag-
CAM was more reliable and correlated better than expert nostic Scale (CDS) it has 5 domains, the striking feature
review.38 The RUCAM by contrast can be used by non- of which was the inclusion of the category of extra hepatic
DILI
experts and physicians in solo practice. Established in manifestation with symptoms of hypersensitivity or im-
1993, it has its limitations, which include the allocation mune allergy such as fever, skin rashes, eosinophilia and ar-
of negative points for multiple drugs and for rechallenge, thralgia. Excluded were factors such as alcohol, age,
often resulting in underestimating causality. This is partic- competing drugs, pregnancy, and the pattern of liver dis-
ularly problematic for drugs used in the treatment of tu- ease such as hepatocellular, cholestatic and mixed. Lucena
berculosis, which includes three hepatotoxic drugs et al performed a comparison between the 2 models and
namely, isoniazid (INH), rifampicin (RIF), and pyrazina- concluded that RUCAM had an overall better performance
mide (PZA). When given together, it is impossible to iden- and was more reliable and consistent.38 More recently
tify the implicated drug in cases of hepatotoxicity. Rockey et al compared the DILIN expert opinion criteria
Furthermore, most patients ($90%) when rechallenged with RUCAM, and found that the DILIN expert opinion
with these drugs tolerate the drugs without developing process produced higher agreement rates and likelihood
DILI. The mechanism of tolerance is not clear unknown scores; however, there was considerable interobserver vari-
and the reasons behind the breakdown of tolerance is a sub- ation with a kappa score of 0.28–0.38.35 A recent expert
ject of much investigation.25,26 meeting in 2011, observed that RUCAM with certain mod-
A recent publication has attempted to rectify some of ifications was still the most widely used causality assess-
the limitations with RUCAM.27 For example, in patients ment method.27
with DILI exposed to combination antituberculous agents
(isoniazid, rifampicin and pyrazinamide), all 3 drugs are
taken as a single entity in causality assessment.26 This ap- PATHOGENESIS OF DRUG-INDUCED
pears reasonable given the interactive and overlapping tox- HEPATITIS
icities between the individual drugs. The exact mechanism of DILI is unknown.39–45 They
Roussel Uclaf Causality Assessment Method (RUCAM): depend upon whether the hepatotoxicity is predictable or
The RUCAM was established following an international idiosyncratic (Table 4). The predictable (or dose depen-
meeting of 12 European and American experts organized dent) hepatotoxicity exemplified by paracetamol toxicity
by the Council for International Organization of Medical has been extensively investigated in animal models. Al-
Sciences (CIOMS) in 1990.23 The RUCAM score has a set though safe in appropriate doses, paracetamol produces
of 7 domains which include time of onset of liver disease, massive hepatocellular necrosis when consumed in large
duration of disease, risk factors, concurrent use of drugs, doses. Its toxic metabolite N-acetyl-p-benzoquinone imine
Journal of Clinical and Experimental Hepatology | September 2012 | Vol. 2 | No. 3 | 247–259 251
7. JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
MITOCHONDRIAL HEPATOTOXICITY the RUCAM score. Recent reports show that no age is ex-
Drugs responsible for mitochondrial toxicity include tetra- empt from DILI. Reports from Scandinavian countries
cycline, valproate, amiodarone, and nucleoside analogs and Japan had a disproportionately large number of el-
such as zalcitabine, didanosine, stavudine, lamivudine, zi- derly people with DILI. This is likely due to the demo-
dovudine and abacavir.51 Mitochondrial toxicity is charac- graphics of those countries and cannot be generalized
teriZed by mild elevation of liver enzymes with (See Table 1). Interestingly drug-induced acute liver fail-
microvesicular steatosis; yet can be accompanied by lactic ure (DIALF) is commonly seen in the relatively young in
acidosis and acute liver failure. Valproate hepatotoxicity India.14,17 Although considered rare, two reports of
may also results in mitochondrial dysfunction due to inhi- DILI in children have recently been described.16,59
bition of mitochondrial beta-oxidation of fatty acids.52 Report from India show that both children and adults
are at risk. In the Indian series, the investigators
observed DILI in 8.7% of their children ranging from 3
PATHOGENESIS OF DRUG-INDUCED years to 17.16 Combination antituberculosis drugs and
CHOLESTASIS antiepileptics were the leading causes in children.16 The
Drug-induced cholestasis may result from defect in bile increasing recognition of children is further corroborated
formation in the hepatocyte or impairment of bile secre- from the DILIN.59 The type of drugs producing DILI in
tion or flow at the bile duct level. The retention of bile acids children and adults appears geographically linked. Anti-
leads to liver injury. At the histopathologic level, drug- tuberculosis drugs are the commonest cause of DILI
induced cholestasis may be bland or canalicular.29 In bland and DIALF in India14,17; contrastingly, antibiotics are
cholestasis there is no histological evidence of inflamma- the commonest cause of DILI in the West followed by
tion, whereas in the latter bile duct and surrounding hepa- paracetamol as a cause of DIALF.12
tocellular inflammation and necrosis may be present.53
Bland cholestasis is produced by inhibition of bile salt Gender
pumps or transporters and is exemplified by drugs such Women are generally considered more at risk for DILI.
as anabolic steroids, estrogens, danazol, cyclosporine, gli- Studies from Japan and Sweden found women constitut-
benclamide and rifampicin. In hepatocanalicular cholesta- ing 58% and 56% of all cases of DILI respectively and again
DILI
sis, the drug metabolite undergoes canalicular excretion, may suggest demographic peculiarity of those coun-
exposing the ductular cells to toxic injury and the tries.20,21 This was not corroborated by series from Spain
onslaught of immune cells. Examples include amoxicil- (49%),18 USA (48%)19 and India (42%).9 However, women
lin–clavulanic acid, chlorpromazine, and erythromycin appear more at risk for DIALF across most studies.14,18,19
antibiotics. Cholangiocyte injury from the toxic metabo-
lites excreted in bile is exemplified by flucloxacillin and ter-
binafine.54,55 This type of injury has a small but definite Alcohol
risk of developing into vanishing bile duct syndrome. While alcohol is believed to be a risk factor for DILI, its ex-
Both genetic and environmental factors in concert play act role is debatable. It is unclear which attribute of alco-
a role in drug-induced cholestasis. The rate limiting step holism is contributory: whether current or past use or
in bile formation is considered to be bile salt export pump the presence of underlying liver disease. Chronic use of al-
(BSEP) mediated translocation of bile salts across the cana- cohol particularly with under nutrition depletes glutathi-
licular hepatocyte membrane.56 Polymorphism of the bile one stores but a definite link between alcoholism is
acid transporters or pumps such as BSEP and multi-drug re- lacking.60 In the DILIN study alcohol was a negative pre-
sistance proteins (MRP) when under stress by xenobiotic or dictor for DILI.19
drug metabolites could manifest as cholestasis in suscepti-
ble individuals.57 There is emerging literature of the role
Concomitant Medication or Polypharmacy
of nuclear receptors, farnesoid X receptor (FXR), pregnane
X receptor (PXR), and constitutive androstane receptor The interaction between drugs given concomitantly is
(CXR) in the pathogenesis of drug-induced cholestasis.58 complex and challenging and complicates causality assess-
ment. Often drugs may have reciprocal interaction such
RISK FACTORS that either drug increases the potential for hepatotoxicity
of the other.61 For example, carbamazepine and INH cause
The following are some of the risk factors attributable to inhibition of metabolism of either drug thereby increasing
DILI. the blood levels of each of the drug.62 The complexity of
concomitant medication is further illustrated by the com-
Age bination chemotherapeutics in tuberculosis. Pyrazina-
Older age was traditionally thought as a risk factor for mide, isoniazid and rifampicin are hepatotoxic in
DILI, such that older age (>55 years) fetches points in decreasing order of propensity.63 The combination of
Journal of Clinical and Experimental Hepatology | September 2012 | Vol. 2 | No. 3 | 247–259 253
9. JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
and biochemical expression of DILI,85,86 and in some may are invaluable and cheap. Given the questionable potency
have a protective role in DILI. This explains the varied of the alternative second line drugs, rechallenge with the pri-
presentations of DILI and why some individuals develop mary drugs with or without PZA either simultaneously or
a particular pattern of hepatitis.87 Yet, despite these ad- sequentially is the usual practise.94,95 Tolerance to
vances, its utility in clinical practise is limited because of antituberculosis drugs could be a result of adaptation or
the low predictive value.86 a change in the environmental factors.31,45
In a GWAS study, Daly et al in a European cohort Various guidelines have been in place for monitoring of
found an 80 fold increased risk in susceptibility to flu- patients with anti-TB drugs.25 They differ with regard to
cloxacillin hepatotoxicity in the presence of HLA- need for initial evaluation of baseline liver biochemical
B*5701.88 This drug is widely available in Europe and tests and the subsequent monitoring of these tests during
5% of the population carry this haplotype. Therefore, gen- therapy and the type of drugs to be reintroduced after hep-
eralizability to other population may be an issue. Interest- atotoxicity. Despite these recommendations, monitoring is
ingly HLA-B*5701 is also strongly associated with often inadequate and underutilized even in those at risk
abacavir hypersensitivity and can assist physicians in for disease.
identifying patients at risk of developing adverse reac-
tions. Individuals with HLA-B*1502 are at increased
PREVENTION OF DRUG-INDUCED LIVER
risk of developing carbamazepine induced Stevens–John-
son syndrome and toxic epidermal necrosis particularly INJURY
in Asians.71 Given the idiosyncratic nature of most drugs, it is difficult
to predict who and when during the course of treatment
Dose will develop hepatotoxicity. Rational drug prescribing is
central to minimizing DILI particularly in patients with
Although idiosyncratic DILI is by definition caused by the risk factors such as old age, comorbid diseases, HIV status,
unique characteristics of the host and not the drug, Lam- daily dose of drug >50 mg, or poly pharmacy.14–
mert et al made an interesting observation regarding 17,59,68,73,74,86,87
Caution should be exercised in the
dose of exposed drug and hepatotoxicity.89 They observed empirical treatment for tuberculosis given the high
that drugs administered in doses >50 mg confers an in- incidence of severe DILI including acute liver failure.
DILI
creased risk for DILI.89 Additionally, drugs metabolized Knowledge of drug–drug interaction and drug–disease
by the liver with its excretion in biliary canaliculi appear interaction is also important. Except for few drugs such
to enhance the risk of DILI.90 as methotrexate, clinically significant DILI is usually
accompanied by symptoms, such that vigilance for
symptoms is the key in the detection of early onset DILI.
RECHALLENGE Patients and caregivers should be educated about the
Rechallenge risk may be related to the drug-specific mecha- development of new symptoms such as nausea, vomiting,
nism of injury.91 The re-occurrence of DILI, following re- anorexia, dark urine or jaundice. The suspected drug or
challenge to the same drug is variable and probably drugs should be stopped at the slightest suspicion of
underreported.92 When alternate drugs are available, it DILI, in order to prevent progressive liver damage.
may not be justifiable to use the implicated drug. However, Debate continues about the need and the timing of liver
when alternate drugs are not available or the alternate drugs function tests particularly in those who need to be on
are less effective such as in TB, the implicated drug/drugs medications for a long duration. There is no clear
may be reintroduced cautiously. In TB, rechallenge with evidence that such a practise influences much in the
the original drugs is common. A distinction may be made detection or prevention of clinically significant liver
however, wherein drugs that produce metabolic idiosyn- injury. Additional constraints include the costs and
crasy such as antituberculous drugs rarely produce DILI inconvenience of the tests, physician ambiguity and
on rechallenge. Rechallenge with drugs that produced im- varying guidelines with regard to timing of the tests.
munoallergic manifestations such as skin rashes, fever, Studies by Lammert et al have clearly shown the
lymphadenopathy or eosinophilia is fraught with a potential importance of dose dependent hepatotoxicity.86
risk of a severe reaction with a shorter latency period. Often Patients receiving methotrexate for psoriasis are re-
reactions could also occur to cross reacting drugs. Prime ex- ported to be at increased risk for fibrosis and/or cirrhosis,
amples in this category are the AED (antiepileptic drugs) such that serial liver biopsies have been recommended.96
such as phenytoin, carbamazepine and phenobarbitone.93 Subsequent studies have questioned the effectiveness of
With the advent of newer anti-epileptic drugs such as levetir- liver biopsies in detecting advanced liver fibrosis and its im-
acetam and clobazam, both having a better safety profile, pact on patient management.97 Increasing evidence attests
DILI following exposure to AED may be less of a challenge to the role of host and environmental factors such as obe-
in the future. For tuberculosis though, the primary drugs sity, diabetes mellitus, alcohol or concomitant medications
Journal of Clinical and Experimental Hepatology | September 2012 | Vol. 2 | No. 3 | 247–259 255
11. JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
9. Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, 30. Shapiro MA, Lewis JH. Causality assessment and drug-induced
Adarsh CK. Single-center experience with drug-induced liver injury hepatotoxicity: promises and pitfalls. Clin Liver Dis. 2007;
from India: causes, outcome, prognosis, and predictors of mortal- 11:477–505.
ity. Am J Gastroenterol. 2010;105:2396–2404. 31. Senior JR. Monitoring for hepatotoxicity: what is the predictive
10. Vuppalanchi R, Liangpunsakul S, Chalasani N. Etiology of new- value of liver “function” tests? Clin Pharmacol Ther. 2009;85:
onset jaundice: how often is it caused by idiosyncratic drug- 331–334.
induced liver injury in the United States? Am J Gastroenterol. €
32. Bjornsson E, Davidsdottir L. The long-term follow-up after idiosyn-
2007;102:558–562. cratic drug-induced liver injury with jaundice. J Hepatol. 2009;
11. Hussaini SH, O'Brien CS, Despott EJ, Dalton HR. Antibiotic ther- 50:511–517.
apy: a major cause of drug-induced jaundice in southwest En- 33. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating
gland. Eur J Gastroenterol Hepatol. 2007;19:15–20. the probability of adverse drug reactions. Clin Pharmacol Ther.
12. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced 1981;30:239–245.
acute liver failure: results of a United States multicenter, prospec- 34. Maria VA, Victorino RM. Development and validation of a clinical
tive study. Hepatology. 2005;42:1364–1372. scale for the diagnosis of drug-induced hepatitis. Hepatology.
13. Reuben A, Koch DG, Lee WM. Drug-induced acute liver failure: re- 1997;26:664–669.
sults of a U.S. multicenter, prospective study. Hepatology. 35. Rockey DC, Seeff LB, Rochon J, et al. Causality assessment in
2010;52:2065–2076. drug-induced liver injury using a structured expert opinion process:
14. Kumar R, Shalimar, Bhatia V, et al. Antituberculosis therapy- comparison to the Roussel-Uclaf causality assessment method.
induced acute liver failure: magnitude, profile, prognosis, and pre- Hepatology. 2010;51:2117–2126.
dictors of outcome. Hepatology. 2010;51:1665–1674. 36. Sarda P, Sharma SK, Mohan A, et al. Role of acute viral hepatitis
15. Devarbhavi H, Kremers W. Fulminant hepatic failure: cause, as a confounding factor in antituberculosis treatment induced
course and predictors of outcome. Ind J Gastroenterol. 2005; hepatotoxicity. Indian J Med Res. 2009;129:64–67.
24(suppl 1):A116. 37. Davern TJ, Chalasani N, Fontana RJ, et al. Acute hepatitis E infec-
16. Devarbhavi H, Karanth D, Prasanna KS, Adarsh CK, Patil M. Drug- tion accounts for some cases of suspected drug-induced liver in-
Induced liver injury with hypersensitivity features has a better out- jury. Gastroenterology. 2011;141:1665–1672.
come: a single-center experience of 39 children and adolescents. 38. Lucena MI, Camargo R, Andrade RJ, Perez-Sanchez CJ, Sanchez
Hepatology. 2011;54:1344–1350. De La Cuesta F. Comparison of two clinical scales for causality as-
17. Devarbhavi H, Dierkhising R, Kremers WK. Antituberculosis ther- sessment in hepatotoxicity. Hepatology. 2001;33:123–130.
apy drug-induced liver injury and acute liver failure. Hepatology. 39. Tujios S, Fontana RJ. Mechanisms of drug-induced liver injury: from
2010;52:798–799. bedside to bench. Nat Rev Gastroenterol Hepatol. 2011;8:202–211.
18. Andrade RJ, Lucena MI, Fernandez MC, et al. Spanish group for 40. Holt MP, Ju C. Mechanisms of drug-induced liver injury. AAPS J.
the study of drug-induced liver disease. Drug-induced liver injury: 2006;8:E48–E54.
DILI
an analysis of 461 incidences submitted to the Spanish registry 41. Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Saf.
over a 10-year period. Gastroenterology. 2005;129:512–521. 2007;30:277–294.
19. Chalasani N, Fontana RJ, Bonkovsky HL, et al. Drug induced liver 42. Mehal WA, Azzaroli F, Crispe IN. Immunology of the healthy liver: old
injury network (DILIN). Causes, clinical features, and outcomes questions and new insights. Gastroenterology. 2001;120:250–260.
from a prospective study of drug-induced liver injury in the United 43. Bjornsson E, Kalaitzakis E, Olsson R. The impact of eosinophilia
States. Gastroenterology. 2008;135:1924–1934. and hepatic necrosis on prognosis in patients with drug-induced
20. Bjornsson E, Olsson R. Outcome and prognostic markers in sever liver injury. Aliment Pharmacol Ther. 2007;25:1411–1421.
drug-induced liver disease. Hepatology. 2005;42:481–489. 44. Matzinger P. Tolerance, danger, and the extended family. Annu
21. Takikawa H, Murata Y, Horiike N, Fukui H, Onji M. Drug-induced Rev Immunol. 1994;12:991–1045.
liver injury in Japan: an analysis of 1676 cases between 1997 45. Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Dis-
and 2006. Hepatol Res. 2009;39:427–431. cov. 2005;4:489–499.
22. Benichou. Criteria of DILI. Report of an international consensus 46. Shayiq RM, Roberts DW, Rothstein K, et al. Repeat exposure to
meeting. J Hepatol. 1990;11:272–276. incremental doses of acetaminophen provides protection against
23. Danan G, Benichou C. Causality assessment of adverse reactions acetaminophen-induced lethality in mice: an explanation for high
to drugs – I. A novel method based on the conclusions of interna- acetaminophen dosage in humans without hepatic injury. Hepatol-
tional consensus meetings: application to drug-induced liver in- ogy. 1999;29:451–463.
juries. J Clin Epidemiol. 1993;46:1323–1330. 47. Deng X, Luyendyk JP, Ganey PE, Roth RA. Inflammatory stress and
24. Fontana RJ, Seef LB, Andrade RJ, et al. Standardization of nomen- idiosyncratic hepatotoxicity: hints from animal models. Pharmacol
clature and causality in drug-induced liver injury: summary of a clin- Rev. 2009;61:262–282.
ical research workshop. Hepatology. 2010;52:730–742. 48. Shaw PJ, Ganey PE, Roth RA. Idiosyncratic drug-induced liver injury
25. Saukkonen JJ, Cohn DL, Jasmer RM, et al. Hepatotoxicity of anti- and the role of inflammatory stress with an emphasis on an animal
tuberculosis therapy subcommittee. Am J Respir Crit Care Med. model of trovafloxacin hepatotoxicity. Toxicol Sci. 2010;118:7–18.
2006;174:935–952. €
49. Bjornsson E, Talwalkar J, Treeprasertsuk S, et al. Drug-induced
26. Verma S, Kaplowitz N. Diagnosis, management and prevention of autoimmune hepatitis: clinical characteristics and prognosis.
drug-induced liver injury. Gut. 2009;58:1555–1564. Hepatology. 2010;51:2040–2048.
27. Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phe- 50. Suzuki A, Brunt EM, Kleiner DE, et al. The use of liver biopsy eval-
notype standardization in drug-induced liver injury. Clin Pharmacol uation in discrimination of idiopathic autoimmune hepatitis ver-
Ther. 2011;89:806–815. sus drug-induced liver injury. Hepatology. 2011;54:931–939.
28. Temple R. Hy's law: predicting serious hepatotoxicity. Pharmacoe- 51. Kakuda TN. Pharmacology of nucleoside and nucleotide reverse
pidemiol Drug Saf. 2006;15:241–243. transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther.
29. Zimmerman HJ. Hepatotoxicity: The Adverse Effects of Drugs and 2000;22:685–708.
Other Chemicals on the Liver. 2nd ed. Philadelphia, PA: Lippincott 52. Lheureux PE, Hantson P. Carnitine in the treatment of valproic
Williams and Wilkins; 1999. acid-induced toxicity. Clin Toxicol (Phila). 2009;47:101–111.
Journal of Clinical and Experimental Hepatology | September 2012 | Vol. 2 | No. 3 | 247–259 257
13. JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
95. Tahaoðlu K, Ataç G, Sevim T, et al. The management of anti-
102. Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N,
tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. Cabot C. Treatment of amatoxin poisoning: 20-year retrospective
2001;5:65–69. analysis. J Toxicol Clin Toxicol. 2002;40(6):715–757.
96. Roenigk Jr HH, Auerbach R, Maibach H, Weinstein G, Lebwohl M. 103. Bohan TP, Helton E, McDonald I, et al. Effect of L-carnitine treat-
Methotrexate in psoriasis: consensus conference. J Am Acad Der- ment for valproate-induced hepatotoxicity. Neurology. 2001;56:
matol. 1998;38:478–485. 1405–1409.
97. Aithal GP, Haugk B, Das S, Card T, Burt AD, Record CO. Monitoring 104. Stapelbroek JM, van Erpecum KJ, Klomp LW, Houwen RH.
methotrexate-induced hepatic fibrosis in patients with psoriasis: Liver disease associated with canalicular transport de-
are serial liver biopsies justified? Aliment Pharmacol Ther. fects: current and future therapies. J Hepatol. 2010;52:
2004;19:391–399. 258–271.
98. Aithal GP. Dangerous liaisons: drug, host and the environment. 105. Smith LA, Ignacio JR, Winesett MP, et al. Vanishing bile duct syn-
J Hepatol. 2007;46:995–998. drome: amoxicillin–clavulanic acid associated intra-hepatic chole-
99. Rosenberg P, Urwitz H, Johannesson A, et al. Psoriasis patients stasis responsive to ursodeoxycholic acid. J Pediatr Gastroenterol
with diabetes type 2 are at high risk of developing liver fibrosis dur- Nutr. 2005;41:469–473.
ing methotrexate treatment. J Hepatol. 2007;46:1111–1118. 106. van Roon EN, Jansen TL, Houtman NM, Spoelstra P, Brouwers JR.
100. Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine Leflunomide for the treatment of rheumatoid arthritis in clinical
improves transplant-free survival in early stage non-acetaminophen practice: incidence and severity of hepatotoxicity. Drug Saf.
acute liver failure. Gastroenterology. 2009;137:856–864. 2004;27:345–352.
101. Baniasadi S, Eftekhari P, Tabarsi P. Protective effect of N-acetyl- 107. Giannattasio A, D'ambrosi M, Volpicelli M, Iorio R. Steroid therapy
cysteine on antituberculosis drug-induced hepatotoxicity. Eur J for a case of severe drug-induced cholestasis. Ann Pharmacother.
Gastroenterol Hepatol. 2010;22:1235–1238. 2006;40:1196–1199.
DILI
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