Physical Activity and Hepatocellular Carcinoma Outcomes: a Narrative Review of Pre-clinical, Observational, and...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with incidence and mortality projected to rise. Most patients present with advanced or unresectable disease, where treatment efficacy is often constrained by frailty and impaired physical function. As physical function has emerged as a key determinant of treatment eligibility and survival, there is growing interest in physical activity as a supportive intervention in HCC care. This narrative review synthesises observational, pre-clinical, and trial evidence on the role of physical activity in patients with HCC, examining its potential to improve treatment tolerance, quality of life, and survival.

A literature search was conducted across four databases (PubMed, Scopus, Web of Science, Embase) using keywords related to HCC, physical activity, exercise, and survivorship.

Pre-clinical studies reveal multiple mechanisms through which physical activity may enhance anti-tumour responses, including metabolic reprogramming, modulation of oncogenic signalling and immune activation. Observational studies suggest that frailty and sarcopenia - markers of reduced physical function, are possibly associated with early treatment discontinuation and shorter survival in HCC. Preliminary interventional data suggest that structured exercise programmes, delivered in hospital, outpatient, telehealth, or mobile formats, can improve frailty, preserve muscle mass, and may potentially support survival. However, clinical studies to date are limited by small sample sizes, non-randomised designs, and short follow-up periods.

Current evidence provides a biologically plausible and clinically promising rationale for integrating physical activity into HCC care pathways. While findings are encouraging, robust randomised trials are needed to establish efficacy, define optimal exercise regimens, and evaluate long-term outcomes.