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

Background & Aims Alcohol abstinence enables hepatic recompensation in patients with decompensated alcohol-related cirrhosis. This study investigated the incidence, predictors, and impact of abstinence-induced recompensation. Methods This multicentre study included patients with decompensated alcohol-related cirrhosis at time of abstinence until 12/2022. 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 one year, and (iv) restored liver function (Child-Pugh A or MELD <10). Results 633 patients from 17 centres were included (71.7% male; 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; aSHR:2.042), higher aspartate transaminase (aSHR /10 U/L:1.011) and gamma-glutamyltransferase (aSHR /10 U/L: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). 123 patients died during follow-up (56.1% liver-related). No recompensated patient who remained abstinent died of liver-related causes and recompensation was independently linked to lower all-cause mortality (aHR:0.255, p=0.001). Hepatocellular carcinoma (HCC) was diagnosed in 16 patients, yet none from the recompensated cohort. Conclusions Alcohol abstinence enabled recompensation in one third of patients with decompensated alcohol-related cirrhosis, particularly with early abstinence and absence of further decompensation. Recompensation led to a significant survival benefit with maintained abstinence, with a negligible residual risk of liver-related death and HCC. Impact And Implications 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 is maintained. These findings support personalised treatment approaches in decompensated alcohol-related cirrhosis by helping identify patients at risk of progression or with potential for regression.