Alcohol-associated hepatitis (AH) is a severe inflammatory form of alcohol-associated liver disease (ALD) that carries a high mortality rate. Early liver transplantation for severe AH is increasingly available. However, specific criteria for referral and selection remain a subject of debate.

To provide a narrative review of the natural history, diagnostic criteria and indications for referral for early liver transplantation for severe AH.

We searched PubMed for articles published through August 2023. Key search terms were 'alcoholic hepatitis,' 'alcohol-associated hepatitis,' 'abstinence,' 'alcohol relapse,' and 'liver transplantation.'

Previously, a six-month period of alcohol abstinence was required before patients with ALD were considered for liver transplantation. However, studies in recent years have demonstrated that, among carefully selected patients, patients who received early transplants have much higher survival rates than patients with similarly severe disease who did not undergo transplants (77% vs. 23%). Despite these successes, early liver transplantation remains controversial, as these patients have typically not undergone treatment for alcohol use disorder, with the ensuing risk of returning to alcohol use.

While early liver transplantation for AH has survival benefits, many patients would not have received treatment for alcohol use disorder. An integrated approach to evaluating candidacy for early liver transplantation is needed.

Liver transplantation remains the only feasible long-term treatment option for patients with end-stage liver disease. Despite significant medical and surgical advances over the decades, liver transplantation remains a complex undertaking with the need for indefinite immunosuppression and avoidance of patient behaviours that may jeopardize the allograft. Adherence (formerly called "compliance") to medical recommendations in terms of anti-rejection medications and-in the case of alcoholic liver disease, abstinence-is considered a key cornerstone to long-term allograft and patient survival. Not surprisingly, a history of habitual non-adherence is considered a contraindication to liver transplantation, especially re-transplantation. It is often assumed that non-adherence policies are "self-evidential" based on "common sense" and "expert opinion." In fact, non-adherence and its negative effects have been well studied in medicine, including in solid organ transplantation. In this review, we present the evidence that non-adherence to medical advice is clearly associated with worse medical outcomes, supporting the concept that efforts to support patient adherence post-transplant need to be optimized at all times.

Alcohol abstinence before liver transplantation (LT) for alcohol-associated liver disease (ALD) is required for every candidate. Some listed patients might relapse, resulting in LT for patients nonabstinent during the pretransplant period. Long-term survival outcomes of these patients have never been studied. We sought to determine whether alcohol consumption on the day of the LT influenced long-term survival after LT. We conducted a retrospective case-control study among French LT centers. Cases were defined as recipients between January 1995 and December 2007 having positive blood and/or urine alcohol levels the day of LT. Each case was paired with 2 controls corresponding to patients transplanted for ALD during the same trimester. Patients were classified into 3 categories per alcohol consumption: abstainers, occasional or transitory excessive consumers, or patients with a sustained excessive consumption (daily consumption >20-30 g/day). During the study period, 3052 LTs for ALD were conducted in France. We identified 42 cases paired with 84 controls. Median blood alcohol level was 0.4 g/L (range 0.1-4.1 g/L) and median urine alcohol level was 0.2 g/L (range 0.1-2.0 g/L). Median follow-up period until death or censoring was 12.9 years (CI_95% = [12.3; 13.6]). Long-term survival was not different between the groups. Relapse to any alcohol consumption rate was higher in the case group (59.5%) than in the control group (38.1%, odds ratio 2.44; CI_95% = [1.13; 5.27]), but sustained excessive consumption was not significantly different between the groups (33.3% versus 29.8% in case and control groups respectively, χ²  = 0.68). Rates of recurrent cirrhosis and cirrhosis-related deaths were more frequent in the case group. Liver transplantation for nonabstinent patients during the immediate pretransplant period does not result in impaired long-term survival despite higher relapse and recurrent cirrhosis rates.

Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.

A 6-month abstinence from alcohol is usually required before patients with severe alcoholic hepatitis are considered for liver transplantation. Patients whose hepatitis is not responding to medical therapy have a 6-month survival rate of approximately 30%. Since most alcoholic hepatitis deaths occur within 2 months, early liver transplantation is attractive but controversial.

We selected patients from seven centers for early liver transplantation. The patients had no prior episodes of alcoholic hepatitis and had scores of 0.45 or higher according to the Lille model (which calculates scores ranging from 0 to 1, with a score ≥ 0.45 indicating nonresponse to medical therapy and an increased risk of death in the absence of transplantation) or rapid worsening of liver function despite medical therapy. Selected patients also had supportive family members, no severe coexisting conditions, and a commitment to alcohol abstinence. Survival was compared between patients who underwent early liver transplantation and matched patients who did not.

In all, 26 patients with severe alcoholic hepatitis at high risk of death (median Lille score, 0.88) were selected and placed on the list for a liver transplant within a median of 13 days after nonresponse to medical therapy. Fewer than 2% of patients admitted for an episode of severe alcoholic hepatitis were selected. The centers used 2.9% of available grafts for this indication. The cumulative 6-month survival rate (±SE) was higher among patients who received early transplantation than among those who did not (77 ± 8% vs. 23 ± 8%, P<0.001). This benefit of early transplantation was maintained through 2 years of follow-up (hazard ratio, 6.08; P = 0.004). Three patients resumed drinking alcohol: one at 720 days, one at 740 days, and one at 1140 days after transplantation.

Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy. (Funded by Société Nationale Française de Gastroentérologie.).