Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Patients with a History of Bariatric Surgery Are 8 Years Younger at Presentation with Severe Alcoholic Hepatitis.

PURPOSE: Patients with prior bariatric surgery (BS) are at risk to develop alcohol use disorder (AUD) and alcohol-related liver disease (ALD). Severe alcoholic hepatitis (sAH) is one of the most severe manifestations of ALD with a 28-day mortality of 20-50%. The impact of prior BS on patients presenting with sAH was assessed. METHODS: From 01/2008 to 04/2021, consecutive patients admitted to a tertiary referral center with biopsy-proven sAH were included in a database. RESULTS: One hundred fifty-eight sAH patients of which 28 patients had a history of BS (BS group) were identified. Of this BS group, 24 patients underwent a Roux-en-Y gastric bypass (RYGB), 3 a biliopancreatic diversion, 1 an adjustable gastric band, and no patients a sleeve gastrectomy. The proportion of patients with BS increased threefold over time during the study period. Patients in the BS group were significantly younger at diagnosis of sAH (44.3 years vs 52.4 years), were more frequently female, and had a higher body mass index and a higher grade of steatosis on liver biopsy. The correlation between BS and a younger age at diagnosis remained significant in a multivariate regression analysis. There were no differences in disease severity between both groups. Furthermore, there were no differences in corticosteroid response, 28-day, 90-day, or 1-year survival. CONCLUSION: Prior BS is independently associated with a younger age of presentation with sAH, but is not independently associated with a different disease severity or outcome. These findings support the need for early detection of AUD in patients who underwent BS, in particular RYGB.

Trasplante hepático en hepatitis alcohólica aguda: ¿debemos decir que no?

Alcohol liver disease is one of the main indications for liver transplantation (LT). Currently, an abstinence period <6 months is required to include a patient with alcohol liver disease on the waiting list, a period that has not been shown to reduce the risk of relapse. Alcoholic hepatitis is characterized by hepatic decompensation secondary to recent, excessive consumption of alcohol, and LT may be the option in a well-selected group of patients who do not respond to medical treatment, but due to established sobriety intervals are excluded, this requires a change in the criteria established by the committees. We propose an evaluation algorithm to consider alcoholic hepatitis unresponsive to medical treatment for LT.

La enfermedad hepática por alcohol es una de las principales indicaciones de trasplante hepático (TH). Actualmente se requiere un período de abstinencia > 6 meses para incluir a un paciente con enfermedad hepática por alcohol en lista de espera de TH, periodo que no ha demostrado disminuir el riesgo de recaída. La hepatitis aguda por alcohol se caracteriza por una descompensación hepática secundaria a un consumo de alcohol excesivo reciente, y el TH puede ser la única opción en un grupo bien seleccionado de pacientes que no responden al tratamiento médico, pero debido a los intervalos de sobriedad establecidos son excluidos, y esto requiere un cambio en los criterios establecidos por los comités. Proponemos un algoritmo de evaluación para considerar para TH la hepatitis aguda por alcohol no respondedora a tratamiento médico.

Effect of an Integrated Transplantation Mental Health Program on Alcohol Relapse After Liver Transplantation for Severe Alcoholic Hepatitis: A Single-Center Prospective Study.

BACKGROUND: Liver transplantation (LT) for severe alcohol-associated hepatitis (AH) remains controversial due to perceived increased recidivism risk after LT because of a lack of protracted abstinence before LT. Data on risk stratification for alcohol relapse after LT are limited. We sought to evaluate the utility of having a mental health program embedded in a transplantation center in risk assessment for alcohol relapse-free patient survival after LT. METHODS: We conducted a prospective analysis of all patients with a diagnosis of severe AH hospitalized at a single transplant center from April 2015 to April 2020. After a comprehensive mental health risk stratification, patients were either waitlisted for LT or declined for waitlisting. The primary endpoint was alcohol relapse-free patient survival rate for those who received LT. The secondary endpoint compared survival rates between patients who received LT and those who did not. The median follow-up was 10 months. RESULTS: Among the 83 patients included in the study, 54 patients were waitlisted for LT (65%, group 1) and 29 were declined (35%, group 2). Patient characteristics and median Model for End-Stage Liver Disease score on presentation were comparable for both cohorts (36 in group 1, 38 in group 2; P = .8). Group 1 had significantly better Stanford Integrated Psychosocial Assessment for Transplantation total scores (median 40 vs 57; P < .01), presence of social support (100% of patients in group 1 vs 76% in group 2; P < .01), and less prevalence of active tobacco smokers (30% in group 1 vs 66% in group 2; P < .01). For those who were not waitlisted, 72.5% experienced rapid deterioration of hepatic function. Among the 54 patients waitlisted, 29 patients received LT (54%), whereas 19 died while on the waiting list (35%). One- and 3-year patient survival after LT were 92.5% and 92.5%, respectively. The overall and sustained alcohol relapse rates after LT were 10.3% and 3.5%, respectively. CONCLUSION: Severe AH is a complex medical and mental health disease and requires an intense risk assessment for recidivism after LT. Our study shows that an integrated transplantation mental health program provides an accurate risk stratification for alcohol relapse after LT, a successful intervention to mitigate recidivism risk, and optimal short-term alcohol relapse-free patient survival. Future studies should focus on enhancing the guidelines for broader application.

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.

BACKGROUND: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. METHODS: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. FINDINGS: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). INTERPRETATION: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. FUNDING: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

The Role of Liver Transplantation in Alcoholic Hepatitis.

Acute alcoholic hepatitis is a syndrome of jaundice and hepatic decompensation that occurs with excessive alcohol consumption. The diagnosis can be made with a combination of clinical characteristics and laboratory studies, though biopsy may be required in unclear cases. Acute alcoholic hepatitis can range from mild to severe disease, as determined by a Maddrey discriminant function ≥32. Mild forms can be managed with supportive care and abstinence from alcohol. While mild form has an overall good prognosis, severe alcoholic hepatitis is associated with an extremely high short-term mortality of up to 50%. Additional complications of severe alcoholic hepatitis can include hepatic encephalopathy, gastrointestinal bleeding, renal failure, and infection; these patients frequently require intensive care unit admission. Corticosteroids may have short-term benefit in this group of patients if there are no contraindications; however, a subset of patients do not respond to steroids. New emerging therapies, which target hepatic regeneration, bile acid metabolism, and extracorporeal liver support, are being investigated. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Recent studies have demonstrated that early liver transplantation in carefully selected patients with severe alcoholic hepatitis who fail medical therapy can provide a significant survival benefit and yields survival outcomes comparable to liver transplantation for other indications, with 6-month survival rates ranging from 77% to 100%. Alcohol relapse posttransplantation remains an important challenge, and heavy consumption can contribute to graft loss and mortality. Future investigation should address the substantial post-liver transplantation recidivism rate, from improving selection criteria to increasing posttransplantation substance abuse treatment resources.

Challenges and future developments in liver transplantation.

Liver transplantation (LT) has become the treatment of choice for a wide range of liver diseases in both adult and pediatric patients. Until recently, the largest proportion of LT in adults, were performed in patients with hepatitis C (HCV) related cirrhosis. The recent availability of safe and effective direct antiviral agents to cure HCV infection in almost all patients whatever the HCV genotype and severity of liver disease, will reduce the need for LT in this category of recipients. Thus, it is presumed that in the next 1 to 2 decades HCV related liver disease will diminish substantially, whereas non-alcoholic steato-hepatitis (NASH) will correspondingly escalate as an indication for LT. The greatest challenges facing LT remain the limited supply of donor organs, and the need for chronic immunosuppression, which represent the true obstacles to the greater application and durable success of the LT procedure. This review aimed to highlight, in different sections, the main open issues and future developments in LT. These will be focused to explore current and future strategies to maximize the use of limited organs, to offer an update on potential new approaches to immunosuppression and to imagine new indications for LT when the number of patients awaiting transplants for HCV related liver disease is reduced.

Meta-analysis of patient survival and rate of alcohol relapse in liver-transplanted patients for acute alcoholic hepatitis.

PURPOSE: This review investigated survival and alcoholic relapse following liver transplantation (LT) in patients with severe acute alcoholic hepatitis (AH) without 6 months of alcohol abstinence. METHODS: All studies comparing acute AH patients undergoing LT with a control group were included. CENTRAL, MEDLINE, and Web of Science databases were searched. Survival benefits or odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using a random effects model. The study was registered in PROSPERO (CRD42017057971). According to the search results, two separate meta-analyses were performed: meta-analysis A compared early LT with medical therapy alone in patients with severe AH that were not responding to medical therapy and meta-analysis B compared LT outcome in patients with AH and chronic alcoholic cirrhosis (AC). RESULTS: The search yielded 2232 articles. Eight studies were included in the two meta-analyses-two studies in meta-analysis A and six studies in meta-analysis B. The two studies (n = 70) included in meta-analysis A revealed that 1-year patient survival was significantly higher in the LT group compared with the medical therapy-alone group (survival benefit, 15.88; 95% CI, 3.98-63.35; p < 0.0001). The six studies in meta-analysis B (including 1091 patients) showed that 1-year (survival benefit, 1.65; 95% CI, 0.95-2.89; p = 0.08), 3-year (survival benefit, 1.31; 95% CI, 0.79-2.18; p = 0.30), and 5-year survival (survival benefit, 1.54; 95% CI, 0.92-2.56; p = 0.10) were not significantly different between AH and AC groups. There was no significant difference in the rate of alcohol relapse between the groups (OR, 1.26; 95% CI, 0.53-2.96; p = 0.60). CONCLUSIONS: Early LT is a life-saving treatment for AH patients that do not respond to medical therapy. The chance of alcohol relapse after LT is not increased in selected patients.

Liver Transplantation for Severe Alcoholic Hepatitis, Updated Lessons from the World's Largest Series.

BACKGROUND: Six-month sobriety before transplantation for alcoholic liver disease is typically required but poorly supported by data. We initiated a pilot program after a report of liver transplantation for severe alcoholic hepatitis (SAH) in which the 6-month rule was waived. We previously reported early outcomes; we now provide longer follow-up in the largest cohort of early liver transplantation for SAH in the literature to date. STUDY DESIGN: Forty-six carefully selected patients with SAH underwent liver transplantation from October 2012 through July 2017; none had been abstinent for 6 months. We also examined 34 patients with alcoholic cirrhosis who received liver transplants under standard protocols with at least 6 months sobriety. We identified patient characteristics and primary outcomes of patient and graft survival, as well as alcohol recidivism. Secondary outcomes included post-transplantation infection, malignancy, and rejection. RESULTS: Compared with patients with alcoholic cirrhosis, SAH patients were younger and with shorter drinking history and higher Model for End-Stage Liver Disease scores at listing and at transplantation. Of these patients, 46% received preoperative steroids; all were nonresponders by Lille score. At a median follow-up time of 532 days (interquartile range 281 to 998 days), there were no significant differences between groups by log-rank testing of Kaplan-Meier estimates for patient and graft survival or alcohol recidivism. CONCLUSIONS: In the largest cohort of patients reported, outcomes after liver transplantation for SAH had excellent 1-year outcomes, similar to those seen in patients who received transplants with 6 months of sobriety. Recidivism was similar in the 2 groups. Early liver transplantation for SAH represents life-saving therapy for patients with otherwise high mortality, calling into question the utility of the 6-month rule in predicting outcomes in patients receiving transplants for alcoholic liver disease.

Fibrosis in small syngeneic rat liver grafts because of damaged bone marrow stem cells from chronic alcohol consumption.

A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced-size (50%) Lewis rat livers are transplanted into green fluorescence protein transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol-fed Lewis hosts developed fibrosis, whereas no fibrosis was observed in control-fed recipients. Host-derived CD133 + 8-hydroxy-2'-deoxyguanosine (8-OHdG) cells were significantly increased in livers recovered from both alcohol-fed and control recipients, but only alcohol-fed recipients demonstrated co-staining (a marker of oxidative DNA damage). α smooth muscle actin (α-SMA) staining, a marker for myofibroblasts, also co-localized with CD133 + cells only in the livers of alcohol-fed recipients. Immunostaining and polymerase chain reaction analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells (BMSCs) expressing CD133, c-Kit, and chemokine (C-X-C motif) receptor 4 markers and caused oxidative mitochondria DNA (mtDNA) damage. Culture of CD133 + cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8-OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased α-SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in BMSCs of chronic alcohol-fed recipients, and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. Liver Transplantation 23 1564-1576 2017 AASLD.

Three-year Results of a Pilot Program in Early Liver Transplantation for Severe Alcoholic Hepatitis.

OBJECTIVE: To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012. BACKGROUND: Six months of alcohol abstinence is typically required before liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability. METHODS: Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groups: severe alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with ≥6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking. RESULTS: Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for Groups 1 and 2, respectively (P = 0.27). Alcohol relapse was similar in Group 1 versus Group 2: 23.5% versus 29.2% (P > 0.99). Harmful drinking was higher in Group 1 versus Group 2, despite lack of statistical significance: 23.5% versus 11.5% (P = 0.42). CONCLUSIONS: In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary.

Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic 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.

Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients.

Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed.

Liver transplantation in the context of organ shortage: toward extension and restriction of indications considering recent clinical data and ethical framework.

PURPOSE OF REVIEW: The scarcity of liver grafts requires to optimize the results of transplantation. Extensions and alternatives of liver transplantation have to be regularly evaluated. RECENT FINDINGS: Acute-on-chronic liver failure and severe alcoholic hepatitis may represent potential extensions of transplant indications. In these diseases, selected patients could obtain a significant benefit from liver transplantation, whereas long-term outcomes and global impact on waiting lists remain to be evaluated prospectively. Alternatives to transplantation may be represented by recent progress in the management of hepatitis C and the treatment of hepatocellular carcinoma. In hepatitis C, new drug combinations may improve the disease control, reducing the progression to cirrhosis and also the risk of post-transplant reinfection allowing to anticipate a future decrease in the indications for transplantation and retransplantation in these patients. In hepatocellular carcinoma, thanks to improvements in operative techniques and better identification of prognostic factors of cancer recurrency, surgical resection or radiofrequency destruction could appear now as true alternatives to transplant in highly selected patients. SUMMARY: Before implementation of these potential changes into decisional algorithms for listing and organ allocation, their consequences, either for patient's individual benefit or for global transplant outcomes, should be closely evaluated using objective long-term end points and taking into account the ethical recommendations for organ transplantation.

Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

Current management of alcoholic liver disease.

Alcoholic liver disease accounts for significant economic burden with second most common cause for liver transplantation in the US. Although alcohol abstinence is most crucial, morbidity and mortality occur amongst those with continuing alcohol intake and with established end stage liver disease due to lack of specific treatment modalities to manage this disease. Patients with severe acute alcoholic hepatitis, a distinct subset of alcoholic liver disease have a potential for mortality in about 25% within about 1 month despite treatment with available specific agents such as corticosteroids and/or pentoxifylline. Hence, there is clear need for newer and better treatment options to manage these patients. In this article, potential emerging newer targets to manage this disease are discussed including intestinal decontamination, caspase inhibitors, antioxidants, and interlukins. In the background of encouraging emerging data (retrospective data from the UNOS database and data from a case matched prospective French study) on the beneficial effects of liver transplantation amongst patients with alcoholic hepatitis who are non-responders to current medical treatments, this article would also deal controversies surrounding the role and use of liver transplantation in patients with alcoholic hepatitis. Issues such as rule of 6 months of abstinence, ethical issues, and shortage of donor organs will be debated.

Alcoholic hepatitis: Prognosis and treatment.

Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and is the most severe form of alcoholic liver disease. AH occurs in patients with heavy alcohol abuse and underlying liver disease. In its severe form, AH carries a poor short-term prognosis. Although the existence of AH can be strongly suspected based on clinical and biochemical criteria, a definitive diagnosis requires a liver biopsy. There is a clear need to develop non-invasive markers for these patients. The prognosis of patients with AH can be established by different score systems (Maddrey's DF, ABIC, MELD and Glasgow). Recently, a histological scoring system able to estimate prognosis has been developed (Alcoholic Hepatitis Histological Score - AHHS). The management of patients with AH has changed little in the last few decades. In patients with severe form of AH, prednisolone and pentoxifylline are the first line therapy. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Current research is aimed at identifying the main disease drivers and to develop animal models of true AH. For non-responders to medical therapy, the only curative option is to perform a salvage liver transplantation. This particular indication of liver transplantation is currently under debate and prospective studies should evaluate the specific patient evaluation and selection criteria.