Incidence and implications of abstinence-induced recompensation in alcohol-related cirrhosis

Alcohol abstinence enables hepatic recompensation in patients with decompensated alcohol-related cirrhosis. This study investigated the incidence, predictors, and impact of abstinence-induced recompensation.

This multicentre study included patients with decompensated alcohol-related cirrhosis recruited at the time of abstinence up to December 2022. Recompensation was defined by Baveno VII criteria: (i) sustained abstinence (≥3 months), (ii) resolution of ascites and hepatic encephalopathy off therapy, (iii) absence of variceal bleeding for 1 year, and (iv) restored liver function (Child-Pugh A or MELD <10).

A total of 633 patients from 17 centres were included (71.7% male; median age 55 years). Alcohol-associated hepatitis superimposed on cirrhosis was present in 40.8%. Median MELD was 19 (13-24), and 47.2% had progressed to further decompensation at abstinence. Median time from index decompensation to abstinence was 0.2 (0.0-7.6) months. Over a follow-up of 36.3 (19.2-63.2) months, 197 patients (31.1%) achieved recompensation (cumulative incidence: 12.3% at 1 year, 23.4% at 2 years, 33.8% at 5 years). Early abstinence (within 1 month of decompensation; adjusted subdistribution hazard ratio [aSHR] 2.042), higher aspartate aminotransferase (aSHR per 10 U/L increase: 1.011) and gamma-glutamyltransferase (aSHR per 10 U/L increase: 1.004) (all p <0.001) increased recompensation likelihood in both supervised and machine-learning models, while the presence of further decompensation decreased it (aSHR 0.650, p = 0.013). During follow-up, 123 patients died (56.1% liver-related). Recompensation was independently associated with lower all-cause mortality (aHR 0.255, p = 0.001). No recompensated patient who remained abstinent died of liver-related causes or developed hepatocellular carcinoma.

Alcohol abstinence enabled hepatic recompensation in approximately one-third of patients with decompensated alcohol-related cirrhosis, particularly when abstinence was achieved early and in the absence of further decompensation. Recompensation was associated with a substantial survival benefit under sustained abstinence, with a negligible residual risk of liver-related death and hepatocellular carcinoma.

Hepatic recompensation, as defined by Baveno VII, is a novel clinical concept reflecting the potential for disease regression and resolution of decompensating events in patients with cirrhosis once the underlying aetiological factor is removed or controlled. In this multicentre study, sustained alcohol abstinence led to recompensation in one-third of patients with decompensated alcohol-related cirrhosis within 5 years, particularly if abstinence was achieved early and in the absence of further decompensation. Recompensation markedly improved outcomes, with a negligible residual risk of liver-related death and hepatocellular carcinoma when abstinence was maintained. These findings support personalised treatment approaches in decompensated alcohol-related cirrhosis by enabling the identification of patients at risk of progression or with the potential for regression.