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Current Opinion in Organ Transplantation Dec 2017The majority of liver transplantation centers have required patients with alcohol-induced liver disease to demonstrate a period of abstinence (generally 6 months'... (Review)
Review
PURPOSE OF REVIEW
The majority of liver transplantation centers have required patients with alcohol-induced liver disease to demonstrate a period of abstinence (generally 6 months' duration) to qualify for transplant listing. This requirement has excluded patients with alcoholic hepatitis from transplant consideration. Since 2011, several studies have examined the outcomes of patients undergoing liver transplantation with brief abstinence as a lifesaving intervention for alcoholic hepatitis. This review includes each of the recent studies and discusses their implications for general transplant practice.
RECENT FINDINGS
A Medical Literature Analysis and Retrieval System search revealed five published studies - three prospective and two retrospective - pertaining to liver transplantation for alcoholic hepatitis. Among patients with medication-nonresponsive alcoholic hepatitis, those who underwent transplantation had superior survival. Liver recipients with alcoholic hepatitis had comparable survival to those with 6 or more months of abstinence. Their relapse rates were not statistically different in the short term over those transplanted with longer abstinence, although some patients in each prospective cohort relapsed to drinking despite narrow inclusion criteria and extensive pretransplant staff reviews and posttransplant surveillance.
SUMMARY
Liver transplantation is a reasonable treatment consideration for highly selective cases of alcoholic hepatitis. Further research is needed to refine inclusion criteria, address posttransplant relapse prevention interventions, and monitor long-term outcomes.
Topics: Hepatitis, Alcoholic; Humans; Liver Transplantation; Prospective Studies; Recurrence; Retrospective Studies
PubMed: 28937405
DOI: 10.1097/MOT.0000000000000468 -
World Journal of Gastroenterology Nov 2015Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and... (Review)
Review
Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this.
Topics: Acute Disease; Alcohol Drinking; Animals; Bacterial Translocation; Chemokines; Granulocyte Colony-Stimulating Factor; Hepatitis, Alcoholic; Humans; Immunity, Mucosal; Inflammation Mediators; Intestines; Liver; Prognosis; Risk Factors; Signal Transduction; Th17 Cells; Toll-Like Receptors
PubMed: 26576079
DOI: 10.3748/wjg.v21.i42.11904 -
Presse Medicale (Paris, France : 1983) 2018All chronic and excessive consumer of alcohol with recent jaundice should be assessed using a Maddrey's score for severe acute alcoholic hepatitis. Corticosteroids are... (Review)
Review
All chronic and excessive consumer of alcohol with recent jaundice should be assessed using a Maddrey's score for severe acute alcoholic hepatitis. Corticosteroids are the first line of treatment, associated with an appropriate nutritional support and alcohol abstinence. Corticosteroids plus N-acetylcysteine combination improves short-term survival over corticosteroids alone, and could be proposed as a first line therapy. The response to treatment is evaluated at the 7th day of treatment, with the Lille model≤0.45. Prognostic of non-responders to corticosteroids with Lille model>0.45 is dramatically low with 23% survival at 6 month. Early liver transplantation in a selected group of patients with non-response to corticosteroids significantly improves 6th month and long-term survival.
Topics: Acute Disease; Algorithms; Hepatitis, Alcoholic; Humans; Prognosis; Severity of Illness Index
PubMed: 30032921
DOI: 10.1016/j.lpm.2018.05.013 -
Journal of Clinical Gastroenterology Feb 2021The goals of this study were to evaluate trends in hospitalizations and in-hospital mortality among US adults with alcohol-associated cirrhosis and alcoholic hepatitis.
GOALS
The goals of this study were to evaluate trends in hospitalizations and in-hospital mortality among US adults with alcohol-associated cirrhosis and alcoholic hepatitis.
BACKGROUND
Alcohol-associated liver disease contributes to significant liver-related morbidity in the United States, among which inpatient care is a major driver of clinical and economic burden.
METHODS
Using the 2007-2014 National Inpatient Sample, alcohol-associated cirrhosis and alcoholic hepatitis hospitalizations were identified. Survey-weighted annual hospitalization trends were stratified by sex, race/ethnicity, and age and compared using χ2 and Student's t-test methods. Adjusted multivariate logistic regression models evaluated predictors of in-hospital mortality.
RESULTS
Among 159,973 alcohol-associated liver disease hospitalizations, 83.7% had a primary diagnosis of alcohol-associated cirrhosis and 18.4% had a primary diagnosis of alcoholic hepatitis. Sex-specific differences in hospitalizations emerged, with significantly higher hospitalization rates seen in males versus females among both alcoholic hepatitis [incidence rate ratio=3.71, 95% confidence interval (CI): 3.47-4.01, P<0.01] and alcohol-associated cirrhosis (incidence rate ratio=2.68, 95% CI: 2.21-3.71, P<0.01). Differences in hospitalization and mortality by ethnicity were observed for both alcohol-associated cirrhosis and alcoholic hepatitis. African Americans with alcohol-associated cirrhosis had significantly higher in-hospital mortality compared with non-Hispanic whites [odds ratio (OR)=1.13, 95% CI: 1.04-1.24, P<0.01], whereas Native Americans (OR=1.88, 95% CI: 1.06-3.34, P=0.030) and Asian/Pacific Islanders (OR=2.02, 95% CI: 1.00-4.06, P=0.048) with alcoholic hepatitis had significantly higher in-hospital mortality compared with non-Hispanic whites.
CONCLUSIONS
This study demonstrated increasing alcohol-associated cirrhosis and alcoholic hepatitis hospitalizations in the United States. The highest rates were observed in men and among Native American and Hispanic ethnic minorities. Significant ethnicity-specific disparities in mortality were observed.
Topics: Adult; Black or African American; Female; Hepatitis, Alcoholic; Hispanic or Latino; Hospitalization; Humans; Liver Cirrhosis, Alcoholic; Male; United States; White People
PubMed: 32520887
DOI: 10.1097/MCG.0000000000001378 -
Clinics in Liver Disease Feb 2021Liver transplant for severe alcohol-associated hepatitis remains a controversial practice despite evidence for a substantial survival benefit compared with medical... (Review)
Review
Liver transplant for severe alcohol-associated hepatitis remains a controversial practice despite evidence for a substantial survival benefit compared with medical therapy and posttransplant alcohol relapse rates comparable with previously published studies in alcohol-associated cirrhosis. The controversy stems in part from concern regarding patient selection practices, lack of long-term follow-up data, and the potential negative public perception of the practice affecting organ donation. Despite these concerns, it seems that early liver transplant for alcohol-associated hepatitis is increasingly being offered to selected patients across the United States and the world.
Topics: Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Liver Transplantation; Patient Selection; Tissue and Organ Procurement; United States
PubMed: 33978581
DOI: 10.1016/j.cld.2020.08.010 -
Pancreatology : Official Journal of the... Jul 2015Alcoholic hepatitis affects up to one-third of individuals who abuse alcohol and can be associated with high mortality. Although this disorder is characterized by... (Review)
Review
Alcoholic hepatitis affects up to one-third of individuals who abuse alcohol and can be associated with high mortality. Although this disorder is characterized by hepatocellular damage, steatosis and neutrophil infiltration, recent evidence suggests that cholestasis or impaired bile secretion may be a frequent occurrence as well. Bile secretion results from the concerted activity of hepatocytes and cholangiocytes, the epithelial cells that line the bile ducts. Hepatocytes secrete bile acids and conjugated products into the bile canaliculi, which then are modified by cholangiocytes through secretion of bicarbonate and water to give rise to the final secreted bile. Here the molecular mechanisms regulating bile secretion in cholangiocytes are reviewed. Moreover, we discuss how the expression of intracellular Ca(2+) channels might be regulated in cholangiocytes, plus evidence that components of the Ca(2+) signaling machinery are altered in a range of cholestatic diseases of the bile ducts.
Topics: Animals; Bicarbonates; Bile Ducts; Calcium Signaling; Cholestasis; Epithelial Cells; Hepatitis, Alcoholic; Humans
PubMed: 26100660
DOI: 10.1016/j.pan.2015.05.477 -
Minerva Medica Aug 2018Severe acute alcoholic hepatitis (AAH) can lead to a clinical picture with a six-month mortality rate in more than 70% of cases. This clinical picture is characterized... (Review)
Review
Severe acute alcoholic hepatitis (AAH) can lead to a clinical picture with a six-month mortality rate in more than 70% of cases. This clinical picture is characterized by: jaundice with a duration of less than three months, jaundice at the first failure event, serum bilirubin greater than 5 mg/dL, ratio AST/ALT>2/1, AST less than 500 IU/L, ALT<300 IU/L, neutrophil leukocytosis and a GGT increase. In addition, encephalopathy, fever, asthenia and coagulopathy may be present. Its onset may also be characterized by portal-hypertension-related complications, particularly bleeding and hepato-renal syndrome. In cases where there is an overlapping of an acute form characterized by an etiological factor other than that of the base hepatopathy, acute on chronic liver failure (ACLF) is obtained. This can result in systemic inflammation response syndrome (SIRS) with a multi-organ systemic involvement. Several indices are used to evaluate the prognosis, in particular Maddrey's discriminant function (mDF) and the model of end stage liver disease (MELD). In our clinical practice, we use the MELD routinely. In cases of ACLF, a consortium organ failure score (CLIF-COFs) is used. Therapy is characterized by abstention in cases of severe forms (mDF>32 and MELD>21); in the absence of contraindications, steroid therapy is possible. In cases of an unresponsive liver, transplantation is premature. In our view, this possibility, after proper selection, must be offered for both prognostic and ethical reasons.
Topics: Decision Trees; Hepatitis, Alcoholic; Humans; Liver Transplantation; Practice Guidelines as Topic
PubMed: 29115798
DOI: 10.23736/S0026-4806.17.05431-3 -
World Journal of Gastroenterology Sep 2014Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical... (Review)
Review
Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality. About 20% of patients presenting with alcoholic hepatitis have concomitant HCV infection. Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage. Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection. The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.
Topics: Adrenal Cortex Hormones; Antiviral Agents; Comorbidity; Hepacivirus; Hepatitis C; Hepatitis, Alcoholic; Host-Pathogen Interactions; Humans; Prevalence; Risk Factors; Treatment Outcome
PubMed: 25232227
DOI: 10.3748/wjg.v20.i34.11929 -
PloS One 2018We aimed to describe changes in survival in alcoholic hepatitis (AH) over time by examining published data. (Review)
Review
PURPOSE/BACKGROUND
We aimed to describe changes in survival in alcoholic hepatitis (AH) over time by examining published data.
METHODS
A systematic literature search of Ovid Embase and PubMed was undertaken using the MESH terms 'hepatitis, alcoholic' to identify randomised controlled trials (RCT) and observational studies (OS) in alcoholic hepatitis. Data were extracted from included studies regarding 28-day, 90-day, 180-day mortality, as well as biochemical and clinical data.
RESULTS
After review of the literature search results, 77 studies published between 1971 and 2016 were analysed, which included data from a total of 8,184 patients. Overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days after admission. No changes in mortality over time were observed in univariable analysis at 28 days or 90 days after admission (Pearson correlation r -0.216, p = 0.098, and r 0.121 p = 0.503 respectively). A small but statistically significant increase in mortality was seen in 180-day mortality (r 0.461 p = 0.036). However, after meta-regression to adjust for other factors associated with mortality at each time point, no changes in mortality were seen. Sub-group analysis did not reveal any changes in mortality over time in different study types, or when only biopsy-proven or severe disease were considered.
CONCLUSION
There has been no improvement in mortality from AH. This is not explained by changes in severity of disease. This emphasises the urgent need for effective treatments for this alcoholic hepatitis.
Topics: Hepatitis, Alcoholic; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Regression Analysis; Survival Rate
PubMed: 29444123
DOI: 10.1371/journal.pone.0192393 -
Journal of Hepatology Feb 2019In some areas of medicine the clinical development pathway through phase II and III clinical trials has been well mapped out and refined through extensive experience. In... (Review)
Review
In some areas of medicine the clinical development pathway through phase II and III clinical trials has been well mapped out and refined through extensive experience. In contrast, a number of key questions remain unanswered in the development of novel therapeutics for alcoholic hepatitis. The use of mortality as an endpoint in phase II clinical trials will potentially restrict the appeal of this therapeutic area for pharmaceutical companies, as the number of patients required for adequately powered clinical trials becomes impractical. Herein, we discuss alternative endpoints and conclude that dynamic assessment of liver function is the most pragmatic option in early stage studies. Stratification based on disease severity should be applied to avoid uneven distribution of patients with substantially differing mortality risks. Consensus on early phase trial design would help to facilitate new therapeutic development in this area of high unmet medical need.
Topics: Adrenal Cortex Hormones; Clinical Trials as Topic; Drug Discovery; Endpoint Determination; Hepatitis, Alcoholic; Humans; Patient Selection; Prognosis; Risk Factors; Severity of Illness Index
PubMed: 30658732
DOI: 10.1016/j.jhep.2018.11.005