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Gastroenterology Jun 2016Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history... (Review)
Review
Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of other liver diseases by blood and imaging analyses. Liver biopsy specimens, usually collected via the transjugular route, should be analyzed to confirm a diagnosis of AH in patients with an atypical history or presentation. The optimal treatment for patients with severe AH is prednisolone, possibly in combination with N-acetyl cysteine. At present, only short-term increases in survival can be expected-no treatment has been found to increase patient survival beyond 3 months. Abstinence is essential for long-term survival. New treatment options, including liver transplantation, are being tested in trials and results eagerly are awaited.
Topics: Acetylcysteine; Biopsy; Free Radical Scavengers; Glucocorticoids; Hepatitis, Alcoholic; Humans; Liver; Prednisolone; Prognosis
PubMed: 26948886
DOI: 10.1053/j.gastro.2016.02.074 -
Recenti Progressi in Medicina Sep 2017Chronic alcohol related liver disease is characterized by a cascade of events defined as follows: steatosis, steatohepatitis/steatofibrosi, cirrhosis and hepatocellular... (Review)
Review
Chronic alcohol related liver disease is characterized by a cascade of events defined as follows: steatosis, steatohepatitis/steatofibrosi, cirrhosis and hepatocellular carcinoma. On one of these histologic patterns may overlap acute alcoholic hepatitis (AAE) (mild, moderate, severe). Severe AAE can cause a severe clinical picture: jaundice with a duration of less than three months, jaundice in the first decompensation event, serum bilirubin higher than 5 mg/dL, ratio AST/ALT >2:1, AST less than 500 IU/L ALT <300 IU/L, neutrophil leukocytosis and increased GGT. In addition, it is possible the presence of encephalopathy, fever, fatigue, coagulopathy. The onset can also be characterized by portal hypertension-related complications. An extremely severe clinical condition is the superposition of an acute insult to a chronic framework, not necessarily a cirrhotic one. This condition has been termed acute on chronic (acute on chronic liver failure - ACLF:), and it is possible to have a SIRS (systemic inflammation response syndrome) with a multi-organ system involvement. The diagnosis, in selected cases, can be confirmed by a transjugular biopsy that allows to reach a histologic prognostic stratification. Several indices are used for the assessment of prognosis and in particular the MDF and the MELD. In our clinical practice we use the MELD. In case of ACLF, the consortium organ failure score (CLIF-C OFS) is used. The therapy is characterized by alcohol abstention, and, in severe forms (MDF >32 and MELD >21) with absence of contraindications, it is possible to use steroids therapy. If a positive answers cannot be obtained, an early liver transplantation is proposed. This possibility, after a careful selection, now is promoted by several authors.
Topics: Acute Disease; Acute-On-Chronic Liver Failure; Hepatitis, Alcoholic; Humans; Jaundice; Liver Transplantation; Organ Dysfunction Scores; Prognosis; Severity of Illness Index; Steroids; Systemic Inflammatory Response Syndrome
PubMed: 28901345
DOI: 10.1701/2745.27988 -
Digestive Diseases and Sciences Jun 2020Although alcohol-associated liver disease has long been a major component of the liver disease landscape, it was overshadowed by chronic hepatitis C until recently.... (Review)
Review
Although alcohol-associated liver disease has long been a major component of the liver disease landscape, it was overshadowed by chronic hepatitis C until recently. Nevertheless, with the declining incidence of hepatitis C in the wake of highly effective antiviral therapy, attention has shifted to the increasing burden of alcohol-associated liver disease. The incidence of advanced alcohol-associated liver disease, including acute alcoholic hepatitis and alcohol-associated cirrhosis, is rising in parallel with increasing rates of alcohol use disorders. As a result, alcohol-associated liver disease is now one of the most common indications for liver transplantation. Rates of liver transplantation for acute alcoholic hepatitis are rising as well in spite of the sparse guidance regarding candidate selection, counseling, postoperative care, long-term follow-up, and other best practices. To this day, liver transplant for acute alcoholic hepatitis remains a hotly debated clinical controversy.
Topics: Alcoholism; Female; Graft Survival; Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Transplantation; Male; Patient Selection; Treatment Outcome
PubMed: 32107678
DOI: 10.1007/s10620-020-06159-9 -
Scandinavian Journal of Gastroenterology Mar 2021Single nucleotide polymorphisms within the interferon lambda 4 ( gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is...
OBJECTIVES
Single nucleotide polymorphisms within the interferon lambda 4 ( gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients.
METHODS
In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes.
RESULTS
Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients ( = .058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died.
CONCLUSIONS
The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.
Topics: Antiviral Agents; Genotype; Hepacivirus; Hepatitis, Alcoholic; Humans; Interferons; Interleukins; Pilot Projects; Polymorphism, Single Nucleotide
PubMed: 33602032
DOI: 10.1080/00365521.2021.1874046 -
Seminars in Liver Disease Nov 2017Alcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months,... (Review)
Review
Alcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months, treatment options are limited and ineffective. Recent advances on the understanding of the pathomechanisms of AH have identified numerous potential targets for new therapeutic interventions. Many of those targets are currently under preclinical testing and/or in human clinical trials for nonalcoholic steatohepatitis. Thus, the field of AH should be ready to launch new efforts and targeted clinical trials for this underserved patient population. There are remaining challenges in designing clinical trials in AH that include definition of the severity of disease, common data elements in clinical trial design, and selection of clinically meaningful endpoints. Future efforts and consensus meetings between regulatory agencies, academic and clinical experts, and industry will be instrumental to advance this emerging and greatly needed field of clinical investigations.
Topics: Clinical Trials as Topic; Hepatitis, Alcoholic; Humans; Research Design; Treatment Outcome
PubMed: 29272895
DOI: 10.1055/s-0037-1608788 -
Expert Opinion on Pharmacotherapy Jun 2018Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used. (Review)
Review
INTRODUCTION
Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used.
AREAS COVERED
This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH.
EXPERT OPINION
Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.
Topics: Alcohol Abstinence; Alcohol Dehydrogenase; Catalase; Fatty Liver, Alcoholic; Hepatitis, Alcoholic; Humans; Liver Transplantation; Microsomes; Pentoxifylline; Phosphodiesterase Inhibitors; Severity of Illness Index; Treatment Outcome
PubMed: 29708448
DOI: 10.1080/14656566.2018.1465929 -
World Journal of Gastroenterology Apr 2016The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most... (Review)
Review
The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using "Omics" platforms, newer options for patients with alcoholic hepatitis are expected soon.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Drug Resistance; Gastrointestinal Microbiome; Gastrointestinal Tract; Genetic Therapy; Hepatitis, Alcoholic; Humans; Liver Transplantation; Nutritional Support; Pentoxifylline; Prebiotics; Probiotics; Steroids; Treatment Outcome
PubMed: 27099434
DOI: 10.3748/wjg.v22.i15.3892 -
Hepatology International Jul 2016Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. ALD encompasses a spectrum of disorders including asymptomatic... (Review)
Review
Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. ALD encompasses a spectrum of disorders including asymptomatic steatosis, steatohepatitis, fibrosis, cirrhosis and its related complications, and the acute-on-chronic state of alcoholic hepatitis. While multidisciplinary efforts continue to be aimed at curbing progression of this spectrum of disorders, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with severe AH is very high (20-50 % at 3 months). The current therapeutic regimens are limited. The development of new therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of human AH. This review article summarizes the clinical syndrome, pre-clinical translational tools, and pathogenesis of AH at a molecular and cellular level, with the aim of identifying new targets of potential therapeutic intervention.
Topics: Animals; Disease Models, Animal; Hepatitis, Alcoholic; Humans; Molecular Targeted Therapy; Translational Research, Biomedical
PubMed: 27072540
DOI: 10.1007/s12072-015-9701-6 -
Seminars in Liver Disease Feb 2020Alcohol-related liver disease (ALD) is currently the leading indication for liver transplantation in the United States. Among patients with ALD, those with acute... (Review)
Review
Alcohol-related liver disease (ALD) is currently the leading indication for liver transplantation in the United States. Among patients with ALD, those with acute alcoholic hepatitis who do not respond to medical treatment have a 6-month mortality of 70% without transplantation. Despite the high mortality, the majority of patients will not be eligible for transplant, given that most centers follow the 6-month abstinence rule. A handful of centers in Europe and the United States perform early liver transplantation (< 6 months abstinence) in these patients, as it provides a substantial survival benefit. Short-term outcomes for these recipients are favorable, and relapse rates parallel those seen in alcoholic cirrhosis transplant recipients who have completed the 6-month wait period. Moving forward, studies examining long-term outcomes and candidate selection are necessary for this growing subset of liver transplant candidates.
Topics: Alcohol Abstinence; Hepatitis, Alcoholic; Humans; Liver Transplantation; Patient Selection; Risk Factors; Time Factors; Transplant Recipients
PubMed: 31711253
DOI: 10.1055/s-0039-3399560 -
Alcoholism, Clinical and Experimental... Jul 2016Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long-term heavy alcohol use. It is associated with high short-term mortality, economic... (Review)
Review
Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long-term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to (i) describe clinical characteristics and genomics associated with the risk of AH; (ii) discuss role and limitations of liver biopsy and prognostic scoring systems; (iii) summarize evidence regarding the currently available therapies including liver transplantation; and (iv) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through March 2016). The following search engines were used: PubMed, Elsevier Embase, PsycINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population-based, and 43 prospective cohorts) were cited. There are over 325,000 annual admissions with AH contributing to about 0.8% of all hospitalizations in the United States. Liver biopsy may be required in about 25 to 30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episodes. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National Institute on Alcohol Abuse and Alcoholism-funded consortia are awaited for more effective and safer therapies. AH is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for noninvasive biomarkers for the diagnosis, and predicting prognosis and response to therapy.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Hepatitis, Alcoholic; Humans; Liver Transplantation; Models, Biological
PubMed: 27254289
DOI: 10.1111/acer.13108