Variation in attributable fraction of hepatitis B virus and hepatitis C virus among primary liver cancer cases across mainland China: a systematic literature review and meta-analysis

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Aim: Our objective was to describe variations in attributable fractions (AFs) of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) across mainland China. Methods: We conducted a systematic review and meta-analysis of studies published up to July 2024 in PubMed, Embase, WanFang, and China National Knowledge Infrastructure. Eligible studies reported the prevalence of HBV and HCV infection, alone and in combination, in PLC. AFs of HBV, HCV, and non-viral etiology in PLC were estimated by province and, when possible, by sex, age, histological diagnosis, and study periods. Regional and overall AFs were estimated by weighting by provincial and regional population size. Publication bias and heterogeneity were assessed by funnel plots of AFs of HBV, HCV, and non-viral etiology in PLC cases, using Egger test by study size. Results: We included 240 studies with 71,905 PLC cases from 31 provinces, autonomous regions and municipalities across mainland China. AFs of HBV, HCV, and non-viral etiology for PLC across mainland China were 76.5%, 6.6%, and 16.9%, respectively. The AFs of HBV and HCV varied by region, with HBV AFs ranging from 68.7% in Northwest China to 82.9% in South Central China. Respective HCV AFs ranged from 12.7% in Northeast China down to 3.7% in South Central China. Non-viral AFs ranged from 13.4% to 21.0% by region. AFs of non-viral etiology were 57.9% in intrahepatic cholangiocarcinoma (ICC), and AF of HBV was double prevalence ratio (PR), 2.11 (95%CI: 1.89-2.34) in hepatocellular carcinoma (HCC, 76.3%) than ICC (37.3%) cases. Prevalence of HBV was higher in male (83.9%) than female (74.6%) PLC cases, and the mean age at diagnosis was 10 years higher for PLC with HCV (64.9 years) than HBV (54.4 years). Conclusion: HBV, HCV, and non-viral AFs varied substantially by region across China, as well as by sex and age, which can inform strategies for liver cancer prevention and control.