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Current Opinion in Organ Transplantation Apr 2023Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current... (Review)
Review
PURPOSE OF REVIEW
Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current status of transplantation for alcohol-associated hepatitis and the treatment of alcohol use disorder after liver transplantation.
RECENT FINDINGS
Rates of early liver transplantation for alcohol-associated hepatitis are increasing with significant heterogeneity in practices across the Unites States. Recent studies have demonstrated a substantial survival benefit in patients transplanted for alcohol-associated hepatitis with improved outcomes in early vs. late transplantation, first vs. prior hepatic decompensation, and posttransplant abstinence/delayed relapse vs. early return to alcohol use. Several prediction algorithms have been developed to ascertain patients' risk of alcohol relapse and aid in candidate selection, though data on treatment of alcohol use disorders in transplant recipients remains limited.
SUMMARY
Although controversial, early liver transplantation for severe alcohol-associated hepatitis has shown to be a lifesaving intervention. Additional research is needed to evaluate its long-term outcomes, optimize candidate selection, and understand treatment of alcohol use disorder posttransplant.
Topics: Humans; Liver Transplantation; Alcoholism; Hepatitis, Alcoholic; Alcohol Drinking; Recurrence
PubMed: 36512482
DOI: 10.1097/MOT.0000000000001044 -
Clinics in Liver Disease Aug 2021Constitutional, environmental, and genetic risk factors influence the development of alcohol-related cirrhosis. The amount of alcohol consumed and whether excessive... (Review)
Review
Constitutional, environmental, and genetic risk factors influence the development of alcohol-related cirrhosis. The amount of alcohol consumed and whether excessive drinking continues after the identification of pre-cirrhotic liver damage are key risk factors. Female sex, ethnicity, obesity, coffee consumption, cigarette smoking, and exposure to other causes of liver injury also influence the risk of disease development. More recently several genetic loci have been robustly associated with the risk for developing significant alcohol-related liver disease. It remains unclear whether additional risk factors are involved in the development of the clinical syndrome of alcoholic hepatitis, but the genetic evidence is suggestive.
Topics: Alcohol Drinking; Female; Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic
PubMed: 34229837
DOI: 10.1016/j.cld.2021.04.001 -
La Revue Du Praticien Dec 2018Alcoholic hepatitis. In a context of chronic alcoholic intoxication, the diagnosis of alcoholic hepatitis (AH) relies on a histological definition. When it is...
Alcoholic hepatitis. In a context of chronic alcoholic intoxication, the diagnosis of alcoholic hepatitis (AH) relies on a histological definition. When it is symptomatic, AH is a clinical syndrome associating jaundice, moderate fever, sensitivity of the right upper quadrant, loss of appetite and signs of hepatocellular insufficiency in severe forms. Typical biological tests show a moderate cytolysis with predominant AST, a high level of ãGT, and leukocytosis on neutrophils. Rising level of bilirubin and INR rates and low TP ratio are markers of severity of the disease. Regardless, the initial severity, abstinence has a decisive influence on long-term survival. In severe forms (Maddrey ≥ 32), corticosteroid for one month improves short-term survival, which response is evaluated by the Lille score. Accelerated procedure liver transplantation may be offered to some non-responders to medical treatment.
Topics: Adrenal Cortex Hormones; Biomarkers; Hepatitis, Alcoholic; Humans; Liver Transplantation; Severity of Illness Index
PubMed: 30869221
DOI: No ID Found -
Reviews on Recent Clinical Trials 2016Alcohol represents the oldest substance of abuse known and Alcoholic Liver Disease (ALD) is the most common cause of chronic liver disease worldwide. The ALD includes a... (Review)
Review
Alcohol represents the oldest substance of abuse known and Alcoholic Liver Disease (ALD) is the most common cause of chronic liver disease worldwide. The ALD includes a wide spectrum of injury and may lead progressively from simple steatosis to frank cirrhosis. The ALD diagnosis may be hard and it is mainly defined by the history of chronic alcohol intake, physical and laboratory abnormalities suggestive of liver disease. Abstinence is the cornerstone of ALD therapy. Although the burden on health of ALD is not negligible, in the last decades few therapeutic advances have been made. Because of the complex pathogenetic mechanisms, the therapy of ALD and especially of severe Alcoholic Hepatitis (AH), represents a thorny problem in the clinical practice. In severe forms of acute AH, some specific drug treatments, including glucorticoids or pentoxifylline, have been defined and are, at the moment, recommended by international guidelines. On the contrary, specific long-term treatments of ALD, aimed at stopping the progression of fibrosis, are not yet approved.
Topics: Alcohol Abstinence; Hepatitis, Alcoholic; Humans; Obesity; Risk Factors; Sex Factors
PubMed: 27457347
DOI: 10.2174/1574887111666160724183409 -
Digestive and Liver Disease : Official... Jun 2019Alcoholic hepatitis (AH) is a unique clinical syndrome that affects patients with chronic and active harmful alcohol consumption, and is associated with a high mortality... (Review)
Review
Alcoholic hepatitis (AH) is a unique clinical syndrome that affects patients with chronic and active harmful alcohol consumption, and is associated with a high mortality of up to 40% at 1 month from presentation. It is important to assess disease severity and prognosis at time of presentation to identify patients at risk for high mortality and potential candidates for specific therapies. The cornerstone therapy for AH is enteral nutrition and abstinence. Steroids remain the only pharmacological option for severe AH however, adverse effects and lack of long-term benefit limit their routine use. Early liver transplantation is a potential salvage therapy for select severe AH patients. This review article comprehensively covers recent advances on the clinical unmet needs in the field including newer therapies and therapeutic targets, role of liver transplantation, and emerging biomarkers throughout the disease process from diagnosis, assessing prognosis and disease severity, and predicting responsiveness to medical therapies for severe AH.
Topics: Alcohol Abstinence; Alcoholism; Disease Progression; Enteral Nutrition; Hepatitis, Alcoholic; Humans; Liver Transplantation; Prognosis; Steroids; Treatment Outcome
PubMed: 31010745
DOI: 10.1016/j.dld.2019.03.023 -
Journal of Hepatology Feb 2019While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has... (Review)
Review
While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given the high short-term mortality of severe AH, the lack of effective medical therapies and an increasing recognition that the 6-month rule unfairly excluded otherwise favourable candidates, a seminal European pilot study of LT for AH was performed. The success of the European study, which has been corroborated in retrospective analyses from the United States, represented a paradigm shift in therapy for highly selected patients with severe AH who are not responding to medical therapy. However, prospective studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.
Topics: Adult; Alcohol Abstinence; Female; Hepatitis, Alcoholic; History, 20th Century; History, 21st Century; Humans; Liver Transplantation; Male; Middle Aged; Patient Selection; Pilot Projects; Survival Rate; Treatment Outcome
PubMed: 30658734
DOI: 10.1016/j.jhep.2018.11.007 -
The American Journal of Gastroenterology Feb 2022Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease...
INTRODUCTION
Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction.
METHODS
Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days.
RESULTS
In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC.
DISCUSSION
These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.
Topics: Adult; Discriminant Analysis; End Stage Liver Disease; Female; Follow-Up Studies; Global Health; Hepatitis, Alcoholic; Humans; Liver; Liver Function Tests; Male; Middle Aged; Prognosis; ROC Curve; Risk Factors; Severity of Illness Index; Survival Rate; Time Factors
PubMed: 34962498
DOI: 10.14309/ajg.0000000000001596 -
Revista de Gastroenterologia de Mexico... 2020Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response,...
Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.
Topics: Hepatitis, Alcoholic; Humans; Mexico
PubMed: 32532534
DOI: 10.1016/j.rgmx.2020.04.002 -
Journal of Hepatology Jun 2022In recent years, there have been important advances in our understanding of alcohol-associated hepatitis (AH), which have occurred in parallel with a surge in clinical... (Review)
Review
In recent years, there have been important advances in our understanding of alcohol-associated hepatitis (AH), which have occurred in parallel with a surge in clinical trial activity. Meanwhile, the broader medical field has seen a transformation in care paradigms based on emerging digital technologies. This review focuses on breakthroughs in our understanding of AH and how these breakthroughs are leading to new paradigms for biomarker discovery, clinical trial activity, and care models for patients. It portends a future in which multimodal data from genetic, radiomic, histologic, and environmental sources can be integrated and synthesised to generate personalised biomarkers and therapies for patients with AH.
Topics: Biomarkers; Forecasting; Hepatitis, Alcoholic; Humans
PubMed: 35589250
DOI: 10.1016/j.jhep.2022.03.025 -
Current Opinion in Gastroenterology May 2020Alcoholic liver disease continues to be a major public health concern in the United States and around the world. Alcoholic liver disease remains the third most common... (Review)
Review
PURPOSE OF REVIEW
Alcoholic liver disease continues to be a major public health concern in the United States and around the world. Alcoholic liver disease remains the third most common indication for liver transplantation in the United States. Mortality has been reported in up to 30-50% of patients with severe alcoholic hepatitis. Liver transplantation can be lifesaving for patients with alcoholic hepatitis. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence. The majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. The purpose of this review is to provide an update from the most recent peer reviewed articles regarding early liver transplantation of alcoholic hepatitis.
RECENT FINDINGS
This review shows that liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria is a key component for a successful transplant. No change in 1-year graft survival between patients who have 6 months sobriety vs. those transplanted prior to 6 months abstinence. Liver transplantation is limited by very narrow selection criteria and limited long-term data.
SUMMARY
Liver transplantation offers the best survival benefit to patients with alcoholic hepatitis. Selection criteria of patients has evolved and have become more permissive and the period of sobriety has become less important in the evaluation of process. However, long-term outcomes continue to lack in the literature. On the basis of previous studies, patients with longer pretransplant abstinence, disease process insight, older age at the time of transplant, the presence of social support that lives with the patient in the same dwelling place were noted to have lower rates of return to alcohol use after liver transplantation.
Topics: Alcohol Drinking; Glucocorticoids; Graft Survival; Hepatitis, Alcoholic; Humans; Liver Diseases, Alcoholic; Liver Transplantation; Patient Selection; Prognosis; Risk Assessment; Severity of Illness Index
PubMed: 32101986
DOI: 10.1097/MOG.0000000000000623