Predictive and Prognostic Potential of Liver Function Assessment in Patients with Advanced Hepatocellular Carcinoma: A Systematic Literature Review.

Introduction: We conducted a systematic literature review to assess the utility of liver function assessments for predicting disease prognosis and response to systemic anticancer therapy in patients with advanced hepatocellular carcinoma (aHCC). Methods: This was a PRISMA-standard review and was registered with PROSPERO (CRD42021244588). MEDLINE and Embase were systematically searched (March 24, 2021) to identify publications reporting the efficacy and/or safety of systemic anticancer therapy (vs. any/no comparator) in liver-function-defined subgroups in phase 2 or 3 aHCC trials. Screening was completed by a single reviewer, with uncertainties resolved by a second reviewer and/or the authors. English-language full-text articles and congress abstracts were eligible for inclusion. Included publications were described and assessed for risk of bias using the GRADE methodology. Results: Twenty (of 2,579) screened publications were eligible; seven categorized liver function using the albumin-bilirubin system, nine using the Child-Pugh system, four using both. GRADE assessment classified ten, nine, and one publication(s) as reporting moderate-quality, low-quality, and very-low-quality evidence, respectively. Analyses of cross-trial trends of within-exposure arm analyses (active and control) reported a positive relationship between baseline liver function and overall survival and progression-free survival, supporting liver function as a prognostic marker in aHCC. There were also signals for a modest relationship between more preserved baseline liver function and extent of systemic treatment benefit, and with more preserved liver function and lower incidence of safety events. Conclusion: This review supports liver function as a prognostic variable in aHCC and highlights the value of a priori stratification of patients by baseline liver function in aHCC trials. The predictive value of liver function warrants further study. Findings were limited by the quality of available data.