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.