Branched-chain amino acids for people with hepatic encephalopathy.

Systematic review and meta-analysis of randomized trials in people with hepatic encephalopathy, including both overt and minimal disease, most commonly due to cirrhosis. The included studies enrolled adults with alcoholic liver disease, viral hepatitis, and other liver disease etiologies; the pooled analysis covered 16 trials and 827 participants.

Across the included trials, branched-chain amino acids (BCAA) were administered as oral, enteral, or intravenous supplements at varying doses, including fixed doses such as 7.2-29 g/day and 12-40 g/day, or weight-based regimens such as 0.25 g/kg/day and 1.2-1.5 g/kg/day. Treatment durations ranged from 2 days to 2 years and were compared with placebo, isonitrogenous or isocaloric diets, lactulose, neomycin, or other control interventions.

Branched-chain amino acids improved hepatic encephalopathy overall, but did not reduce mortality and did not show clear benefit for quality of life or nutritional outcomes. In pooled analysis, hepatic encephalopathy improved with BCAA versus control (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials), while mortality was unchanged (RR 0.88, 95% CI 0.69 to 1.11; 760 participants; 15 trials). Oral BCAA showed benefit for hepatic encephalopathy (RR 0.67, 95% CI 0.52 to 0.88; 430 participants), whereas intravenous BCAA did not show a clear effect (RR 0.81, 95% CI 0.61 to 1.08; 397 participants). Non-serious gastrointestinal adverse events, including nausea and diarrhoea, were more frequent with BCAA in fixed-effect analysis (RR 5.56, 95% CI 2.93 to 10.55).

The evidence base was heterogeneous, with widely varying BCAA doses, routes, durations, and control conditions across trials. Many studies were small, and outcomes such as quality of life and nutritional parameters were sparsely reported or showed no clear benefit. Results are therefore strongest for short-term improvement in hepatic encephalopathy and weaker for mortality and broader patient-centered outcomes.