# Liver Transplantation Versus Resection for Hepatocellular Carcinoma: An Umbrella and Meta-Meta-Analysis of Published Evidence, 2000–2025

## TL;DR

This study compares liver transplantation and resection for liver cancer, finding that transplantation offers better long-term survival, while resection is a viable option when transplants are not possible.

## Contribution

The study provides a comprehensive umbrella review and meta-meta-analysis resolving inconsistencies in prior meta-analyses of liver cancer treatments.

## Key findings

- Liver transplantation achieves superior long-term overall and disease-free survival compared to liver resection.
- Liver resection may offer comparable short-term outcomes for patients with low recurrence risk or hepatitis C-related disease.
- LT is the preferred treatment for transplant-eligible HCC patients, while LR remains important when donor organs are unavailable.

## Abstract

Liver resection (LR) and liver transplantation (LT) are the two curative surgical options for hepatocellular carcinoma (HCC). Although many meta-analyses have compared these procedures, their conclusions have been inconsistent due to overlapping datasets and methodological heterogeneity. This study provides a comprehensive umbrella review, integrating all available meta-analyses published between 2000 and 2025. We quantitatively pooled hazard ratios from recent large-scale studies and synthesised the overall evidence using a random-effects model. The results clearly demonstrate that LT achieves superior long-term overall and disease-free survival compared with LR, confirming the oncologic benefit of transplantation across Milan and extended criteria. The analysis also highlights that, in patients with low recurrence risk or hepatitis C-related disease, LR may offer comparable short-term outcomes but remains inferior in long-term disease control. By systematically addressing overlap, event-definition heterogeneity, and study quality through AMSTAR-2 appraisal, this review refines previous findings and provides clinicians with a robust, up-to-date synthesis of evidence. The findings support LT as the preferred treatment for transplant-eligible HCC patients, while LR remains an important option when donor organs are unavailable or contraindicated.

Background: Multiple meta-analyses have compared liver resection (LR) with liver transplantation (LT) for hepatocellular carcinoma (HCC), but overlapping primary studies and heterogeneous outcome definitions have complicated interpretation. Methods: A PRISMA/PRIOR-compliant umbrella review (PROSPERO CRD420251069248) was conducted. PubMed, Embase, and CENTRAL were searched for meta-analyses published between 1 January 2000 and 30 September 2025. Quantitative meta-analyses comparing LT and LR were included, while one systematic review of meta-analyses was synthesised narratively. Effect directions were standardised; hazard ratio (HR)-based summaries (LR:LT; values > 1 favour LT) were pooled using random-effects models, whereas odds ratio (OR)-based summaries were described qualitatively because of heterogeneity in endpoint definitions. Results: Four quantitative meta-analyses and one systematic review of meta-analyses met the inclusion criteria. Pooled HRs confirmed LT superiority: overall survival (OS) HR 1.35 (95% CI 1.17–1.55) and disease-free survival (DFS) HR 2.58 (95% CI 2.25–2.96). OR-based summaries from recent meta-analyses were directionally consistent but were not pooled. Conclusions: This umbrella synthesis demonstrates that LT provides superior long-term OS and DFS compared with LR for HCC, with consistent robustness across both Milan and extended selection criteria. Methodological safeguards against study overlap and subgroup insights—including intention-to-treat analyses, viral etiology (hepatitis B virus/hepatitis C virus), era, and geographic region—reinforce LT as the preferred strategy for eligible patients, while LR remains a critical option where graft availability is limited.