Hepatocellular carcinoma risk reduction associated with antiviral treatment in patients with noncirrhotic chronic hepatitis B: a systematic literature review and comparative meta-analysis

Background Chronic hepatitis B (CHB) affects nearly 300 million people worldwide and is a leading cause of hepatocellular carcinoma (HCC). While cirrhosis is a risk factor for HCC, hepatitis B virus (HBV) DNA integration can lead to HCC in non-cirrhotic individuals. This study synthesized existing data to compare HCC risk among non-cirrhotic patients treated with antivirals versus those untreated. Methods A systematic literature review was conducted. Databases were searched in February 2023 and handsearches were performed to identify studies reporting HCC incidence in non-cirrhotic CHB patients, both treated with antivirals for a mean or median duration of at least three years and untreated. A meta-analysis compared HCC incidence rates between treated and untreated populations. Results Two thousand, one hundred sixty-four records were screened and 61 publications on 50 studies were included. HCC cumulative incidence rates increased with greater follow-up, ranging from 0 to 3% at one year and 0 to 30% at 10 years. Incidence rates ranged from 0 per 100 to 2.43 per 100 person-years. The comparative meta-analysis of four studies indicated that treated populations had a 40% reduction in HCC incidence compared to untreated groups (incidence rate ratio [IRR]: 0.59; 95% CI: 0.50, 0.69), with incidence rates expressed per 100 person-years. Sensitivity analyses confirmed the robustness of these findings. Conclusions Antiviral therapy significantly reduces HCC risk in non-cirrhotic CHB patients. These results, with other literature, support treatment guideline expansion to include non-cirrhotic individuals and prevent HCC development. Further research is necessary to evaluate the impact of early versus late treatment initiation and explore potential differences between antivirals. Systematic review registration PROSPERO ID: CRD42023396260. Date of registration: 11 April 2023.