Dynamic skeletal muscle deterioration predicts poorer survival in hepatocellular carcinoma: a systematic review and meta-analysis

Dynamic skeletal muscle deterioration during hepatocellular carcinoma (HCC) treatment may capture changes in host vulnerability during treatment. Yet the available evidence is fragmented across treatment settings, imaging metrics, and definitions of muscle loss, and the magnitude of the prognostic association remains uncertain. We aimed to synthesise the evidence and quantify the association between dynamic skeletal muscle deterioration and overall survival (OS) in patients with HCC. We systematically reviewed prognostic factor studies reporting serial imaging-derived skeletal muscle measurements and adjusted Cox model estimates for OS. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was quantified with the I² statistic and 95% prediction intervals. Prespecified sensitivity analyses and exploratory random-effects meta-regression examined robustness and potential effect modification by treatment type and muscle metric. Fourteen retrospective cohorts comprising 2,844 patients were included, of whom 2,549 contributed to the extracted Cox models. Dynamic skeletal muscle deterioration was significantly associated with poorer OS (random-effects HR 2.28, 95% CI 1.72–3.01; I² = 56%), with a 95% prediction interval of 1.15–4.50. The association remained directionally consistent across all prespecified sensitivity analyses. Exploratory meta-regression did not detect statistically significant differences by treatment modality or muscle metric, but precision was limited. Certainty of evidence was low because of risk of bias, heterogeneity and possible small-study effects. Dynamic skeletal muscle deterioration was associated with an approximately twofold higher hazard of death in HCC and represents a candidate prognostic biomarker requiring prospective validation. Whether serial muscle assessment improves prediction or clinical decision-making remains to be established. The current evidence does not demonstrate that preventing muscle loss improves survival.