Risk prediction models for hepatic encephalopathy in patients with liver cirrhosis: A systematic review and meta-analysis

Background To conduct a systematic review and meta-analysis of existing prediction models for hepatic encephalopathy (HE) in patients with cirrhosis. Methods China National Knowledge Infrastructure (CNKI), WanFang Database, China Science and Technology Journal Database (VIP), SinoMed, PubMed, Embase, Web of Science, Scopus, and the Cochrane Library databases were searched for studies on prediction models for the risk of HE in cirrhosis from inception to April 12, 2025. Two researchers independently conducted the literature search and data extraction, and the quality of the literature was evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST)—meta-analysis using Review Manager 5.4 and Stata 17.0 software. Results Thirty-eight best prediction models from thirty-eight studies were ultimately included in this review. Among them, 17 studies predicted HE after transjugular intrahepatic portosystemic shunt (TIPS). The incidence of HE ranged from 7.2% to 50.4%. The most commonly used predictors were age and Child-Pugh grade/score. The reported area under the curve (AUC) or c-statistic values ranged from 0.667 to 0.969. Thirty-four studies were found to have a high risk of bias, and 27 studies raised applicability concerns, primarily due to inappropriate data sources, limitations in the domain of analysis, and homogenous study populations. Four externally validated logistic regression models had a combined AUC of 0.802 (95% CI: 0.785–0.820), indicating moderate predictive performance. In meta-analysis, age (OR = 1.04, 95% CI: 1.03, 1.05), prior HE (OR = 4.42, 95% CI: 2.67, 7.31), low albumin (OR = 1.78, 95% CI: 1.25, 2.56), total bilirubin (OR = 2.22, 95% CI: 1.73, 2.85), Child-Pugh grade/score (OR = 2.41, 95% CI: 1.87, 3.09; OR = 1.65, 95% CI: 1.16, 2.33, respectively), ascites (OR = 1.96, 95% CI: 1.48, 2.60), and co-infection (OR = 2.57, 95% CI: 1.66, 3.98) were significant predictors of HE in cirrhosis (P < 0.01). Conclusions Prediction models for estimating the risk of incident HE with cirrhosis demonstrate moderate discrimination performance, while with a high overall risk of bias and a lack of clinical effectiveness research. Future research should focus on developing new models through optimised study design and analysis, increased sample sizes and external validation, and applying them to clinical practice. Registration: The protocol for this review was registered on PROSPERO (CRD420251040913).