Oral nutritional interventions associated with reduced clinical events in adults with cirrhosis

BACKGROUND: Liver cirrhosis is a chronic, and progressive condition often complicated by malnutrition, sarcopenia, hepatic encephalopathy (HE), and frailty. Malnutrition is highly prevalent in patients with cirrhosis and is associated with an increased risk of decompensation and mortality. Consequently, leading liver societies (ESPEN, EASL, AASLD) recommend personalized nutritional interventions in patients with cirrhosis. While several studies have examined the effects of BCAAs on clinical and functional outcomes in cirrhosis, few have synthesized these outcomes in a single meta-analysis. Despite a growing number of RCTs on HPHC diets and HMB, existing reviews remain largely limited to sarcopenia-related outcomes. To date, no meta-analysis has evaluated the impact of nutritional interventions on frailty-related outcomes in cirrhosis. AIMS: To assess the impact of oral nutritional interventions, including branched-chain amino acids (BCAAs), high-protein, high-calorie (HPHC) diets, β-hydroxy β-methylbutyrate (HMB), and high-protein diets on clinical and functional outcomes in adults with cirrhosis. METHODS: We conducted a systematic review and meta-analysis of 21 randomized controlled trials (RCTs), of which 18 involving 3128 adults with cirrhosis were included in the meta-analysis, following PRISMA 2020 guidelines. RCTs published between January 1, 2000, and June 1, 2025, involving ≥4 weeks of oral nutritional therapy in patients with cirrhosis were included. Data were pooled using random effects model. Sensitivity, subgroup, and meta-regression analyses explored robustness and potential effect modifiers. The certainty of evidence was assessed using GRADE criteria. RESULTS: Nutritional intervention significantly reduced the risk of overt HE (RR 0.70; 95 % CI 0.52-0.95; NNT 11; I 0 %), liver-related decompensation events (RR 0.69; 95 % CI 0.53-0.90; NNT 16; I 0 %), hospitalization (RR 0.65; 95 % CI 0.49-0.86; NNT 8; I 21.8 %), and mortality (RR 0.64; 95 % CI 0.49-0.84; NNT 23; I 0 %). Handgrip strength improved significantly (MD 2.41 kg; 95 % CI 0.58-4.24; I 87 %), and LFI showed borderline improvement (MD -0.35; 95 % CI -0.70 to -0.0005; I 84.4 %). HPHC diets appeared more effective than BCAAs for mortality and HGS, though comparator bias limits definitive conclusions. Meta-regression indicated greater mortality benefit with higher MELD scores. While studies ≤6 months showed significant mortality reduction, longer-duration studies did not; however, duration was not a significant moderator in subgroup analysis or meta-regression. CONCLUSION: Oral nutritional therapy is associated with reduced risk of decompensation, overt hepatic encephalopathy, hospitalization, and short-term mortality in cirrhosis. While improvements in sarcopenia and frailty were observed, high heterogeneity limits firm conclusions. These findings support current guidelines and highlight the need for longer-duration and head-to-head trials to identify optimal nutritional strategies. PROSPERO REGISTRATION: CRD420251073182.