-
Alcohol and Alcoholism (Oxford,... Jul 2019Alcoholic liver disease (ALD) represents a spectrum of injury, ranging from simple steatosis to alcoholic hepatitis to cirrhosis. Regular alcohol use results in fatty... (Review)
Review
Alcoholic liver disease (ALD) represents a spectrum of injury, ranging from simple steatosis to alcoholic hepatitis to cirrhosis. Regular alcohol use results in fatty changes in the liver which can develop into inflammation, fibrosis and ultimately cirrhosis with continued, excessive drinking. Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality that can occur in patients with steatosis or underlying cirrhosis. The pathogenesis of ALD is multifactorial and in addition to genetic factors, alcohol-induced hepatocyte damage, reactive oxygen species, gut-derived microbial components result in steatosis and inflammatory cell (macrophage and neutrophil leukocyte) recruitment and activation in the liver. Continued alcohol and pro-inflammatory cytokines induce stellate cell activation and result in progressive fibrosis. Other than cessation of alcohol use, medical therapy of AH is limited to prednisolone in a subset of patients. Given the high mortality of AH and the progressive nature of ALD, there is a major need for new therapeutic intervention for this underserved patient population.
Topics: Hepatitis, Alcoholic; Humans; Inflammation Mediators; Kupffer Cells; Reactive Oxygen Species
PubMed: 31219169
DOI: 10.1093/alcalc/agz036 -
Clinics in Liver Disease Feb 2019Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is... (Review)
Review
Alcoholic hepatitis is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by prolonged heavy alcohol use. Treatment is mostly supportive. The short-term prognosis of acute alcoholic hepatitis depends on liver recovery, and ranges widely from rapid improvement to grim multiorgan failure despite treatment. Refinement of scoring systems have enhanced prognostication to guide clinical decision making in alcoholic hepatitis. Recent advances in the treatment of alcoholic hepatitis have solidified corticosteroids as the cornerstone of treatment to enhance short-term survival, but not intermediate or long-term survival.
Topics: Acute Disease; Alanine Transaminase; Aspartate Aminotransferases; Biopsy; Elasticity Imaging Techniques; Glucocorticoids; Hepatitis, Alcoholic; Humans; Jaundice; Liver; Prednisolone; Prognosis; Severity of Illness Index
PubMed: 30454835
DOI: 10.1016/j.cld.2018.09.005 -
The Lancet. Gastroenterology &... May 2020Alcoholic hepatitis is an acute, inflammatory liver disease associated with high morbidity and mortality both in the short term and long term. Alcoholic hepatitis often... (Review)
Review
Alcoholic hepatitis is an acute, inflammatory liver disease associated with high morbidity and mortality both in the short term and long term. Alcoholic hepatitis often arises in patients with a background of chronic liver disease and it is characterised by the rapid onset of jaundice and the development of myriad complications. Medical therapy for severe alcoholic hepatitis relies on corticosteroids, which have modest effectiveness. Abstinence from alcohol is critically important in patients with alcoholic hepatitis, but recidivism is high. Because of the absence of effective medical treatments for alcoholic hepatitis and alcohol dependency, there is a pressing need to develop new and effective therapeutics. Supported by promising preliminary and preclinical studies, many ongoing clinical trials of new therapies for alcoholic hepatitis are currently underway and are discussed further in this Series paper.
Topics: Adrenal Cortex Hormones; Alcohol Abstinence; Alcoholism; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Dietary Supplements; Hepatitis, Alcoholic; Humans; Pentanoic Acids; Probiotics; Receptors, Interleukin-1; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 32277902
DOI: 10.1016/S2468-1253(19)30326-7 -
Clinics in Liver Disease Aug 2021The natural history of moderate alcoholic hepatitis (AH) is not well known. It is a frequent disease with a probable underestimated incidence compared with its severe... (Review)
Review
The natural history of moderate alcoholic hepatitis (AH) is not well known. It is a frequent disease with a probable underestimated incidence compared with its severe form. Among the different prognostic scores predicting short-term mortality in AH, MELD seems to be the most accurate. The mortality of moderate AH is 3% to 7% in the short to medium term and 13% to 20% at 1 year, mainly because of liver-related complications, including severe infections. Long-term abstinence is the main goal of the treatment. There is still need for the development of new therapies for AH, including the less severe forms.
Topics: Hepatitis, Alcoholic; Humans; Incidence
PubMed: 34229838
DOI: 10.1016/j.cld.2021.03.001 -
Clinics in Liver Disease Aug 2021
Topics: Hepatitis, Alcoholic; Humans
PubMed: 34229847
DOI: 10.1016/j.cld.2021.04.003 -
The Medical Clinics of North America May 2023Alcoholic hepatitis (AH) is a unique clinical syndrome on the spectrum of alcohol-associated liver disease (ALD). It constitutes a rising epidemic with increasing... (Review)
Review
Alcoholic hepatitis (AH) is a unique clinical syndrome on the spectrum of alcohol-associated liver disease (ALD). It constitutes a rising epidemic with increasing incidence and major public health implications. In severe AH, 30-day mortality approaches 30%, yet therapeutic options remain limited. Survival benefit from corticosteroids, the mainstay of medical treatment, is short-lived. Among corticosteroid nonresponders, the use of early liver transplantation is heterogeneous across centers and remains limited by significant barriers. Long-term prognosis is largely dictated by abstinence; however, comorbid alcohol use disorder remains undertreated. Efforts to address these challenges are required to curb the AH epidemic.
Topics: Humans; Hepatitis, Alcoholic; Liver Diseases, Alcoholic; Prognosis; Alcohol Drinking; Liver Transplantation; Adrenal Cortex Hormones
PubMed: 37001952
DOI: 10.1016/j.mcna.2022.12.005 -
Clinics in Liver Disease Aug 2021The incidence of alcoholic hepatitis is increasing while the mortality rate remains high. The single current available therapy for severe alcoholic hepatitis is... (Review)
Review
The incidence of alcoholic hepatitis is increasing while the mortality rate remains high. The single current available therapy for severe alcoholic hepatitis is administration of corticosteroids for patients with severe alcoholic hepatitis, which has demonstrated limited benefits, providing a short-term mortality benefit with a marginal response rate. There is a need for developing safe and effective therapies. This article reviews novel therapies targeting various mechanisms in the pathogenesis of alcoholic hepatitis, such as the gut-liver axis, inflammatory cascade, oxidative stress, and hepatic regeneration. Current ongoing clinical trials for alcoholic hepatitis also are described.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Hepatitis, Alcoholic; Humans; Liver Transplantation
PubMed: 34229843
DOI: 10.1016/j.cld.2021.03.006 -
Liver International : Official Journal... Oct 2023Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic... (Review)
Review
Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol-associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short-term mortality. During the COVID-19 pandemic, rates of alcohol-associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol-associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short-term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology-based therapeutic approaches include anti-inflammatory agents, modifications of the gut-liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient-centred treatment approaches to improve prognosis.
Topics: Humans; Hepatitis, Alcoholic; Pandemics; COVID-19; Liver Diseases, Alcoholic
PubMed: 37605624
DOI: 10.1111/liv.15701 -
American Family Physician Apr 1993Anorexia, weight loss, fatigue, symptoms of alcohol withdrawal and hepatomegaly are common early presenting signs and symptoms of alcohol abuse. The clinical diagnosis... (Review)
Review
Anorexia, weight loss, fatigue, symptoms of alcohol withdrawal and hepatomegaly are common early presenting signs and symptoms of alcohol abuse. The clinical diagnosis of alcoholic hepatitis can be made in alcoholics with associated fever, leukocytosis, jaundice and tender hepatomegaly. Associated laboratory abnormalities may include leukocytosis or leukopenia, anemia, a prolonged prothrombin time and elevated liver enzymes, including aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin. An AST-to-ALT ratio greater than 2 is common in patients with alcoholic hepatitis. Liver biopsy may be required to establish the diagnosis and to identify other pathology, such as cirrhosis. Histologic diagnosis of alcoholic hepatitis requires the presence of liver cell damage, an inflammatory infiltrate and fibrosis. Biopsy-proven cirrhosis with alcoholic hepatitis or a significantly elevated total bilirubin level and prolonged prothrombin time are associated with a worse prognosis. Abstinence from alcohol, nutritional supplementation and corticosteroids are the mainstays of treatment for severe alcoholic hepatitis.
Topics: Hepatitis, Alcoholic; Humans
PubMed: 8465712
DOI: No ID Found -
The New England Journal of Medicine Jun 2009
Review
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Diagnosis, Differential; Hepatitis, Alcoholic; Humans; Liver; Liver Transplantation; Pentoxifylline; Phosphodiesterase Inhibitors; Severity of Illness Index; Temperance; Tumor Necrosis Factor-alpha
PubMed: 19553649
DOI: 10.1056/NEJMra0805786