Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis

Background & Aims: Older adults have lower treatment eligibility and worse survival across cancer types; however, the association between age and outcomes in patients with hepatocellular carcinoma (HCC) has not been well characterized. Methods: We performed a search of the PubMed, Ovid MEDLINE, and EMBASE databases from January 2000 to July 2022 to identify studies reporting tumor stage, curative treatment, and overall survival among patients with HCC, stratified by age. Using the DerSimonian and Laird method for a random-effects model, we calculated pooled risk ratios (RRs) for curative treatment receipt and hazard ratios (HRs) for overall survival among younger and older patients (per age thresholds in each study). Results: We identified 103 studies (n = 154,152 patients) that reported outcomes in younger vs. older patients with HCC. Younger patients were more likely to undergo curative treatment (RR 1.48, 95% CI 1.24-1.77; I-2 = 99%), although few studies reported treatment among those with early-stage HCC. Younger patients had better survival than older patients (HR 0.87, 95% CI 0.83-0.92; I-2 = 89%), which was consistent in subgroups using age thresholds of <70 years (HR 0.94, 95% CI 0.89-0.99; I-2 = 78%) and <75 years (HR 0.83, 95% CI 0.70-0.98; I-2 = 79%). Younger patients also had better survival in studies of patients with early-stage HCC (HR 0.78, 95% CI 0.65-0.94; I-2 = 60%) and those undergoing curative therapy (HR 0.87, 95% CI 0.77-0.98; I-2 = 87%). Conclusions: Older patients with HCC are less likely to receive curative treatment and have worse survival than their younger counterparts. Studies to identify factors associated with worse prognosis can inform intervention targets. (c) 2025 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).