A Cochrane review of six randomized clinical trials involving 364 participants evaluated various forms of gene therapy for unresectable hepatocellular carcinoma. The included studies used different viral-based gene therapy platforms, often combined with standard treatments such as liver transplantation or chemotherapy, but the available evidence remained highly uncertain due to small sample sizes, inconsistent outcome reporting, and high risk of bias. Across comparisons—including Pexastimogene devacirepvec, adenovirus-thymidine kinase regimens, and p53-based therapies—data showed no reliable evidence of improved overall survival, reduced serious adverse events, or meaningful changes in quality of life.
The review reported that while some single trials suggested possible survival benefits in specific combinations, the certainty of evidence was very low to low, preventing firm conclusions. Many outcomes, including serious adverse events and quality of life, were not adequately reported, and results were too heterogeneous for meta-analysis. Overall, current data do not establish whether gene therapy meaningfully improves or worsens outcomes for adults with advanced hepatocellular carcinoma, underscoring the need for robust, adequately powered trials and clearer reporting to determine its clinical value.