Alcohol intake, viral hepatitis B infection, viral hepatitis C infection, and the risk of primary liver cancer: systematic review and meta-analysis

Abstract

Background Liver cancer is a leading cause of morbidity and mortality globally. Accurate estimation of the contribution of major risk factors of liver cancer namely, alcohol intake and viral hepatitis infection, is essential for guiding health policy. We undertook a systematic literature review and meta-analysis to calculate unbiased relative risk estimates for each risk factor. Methods We systematically collected published data on relative risks of liver cancer related to intake of alcohol and viral hepatitis B and C infections. For each risk factor, we used meta-regression techniques to estimate the relative risk adjusted for the other two risk factors. In the case of alcohol intake, we used first degree fractional polynomials to choose the best model. In the case of viral hepatitis, we adjusted for alcohol using country-level alcohol data. We assessed for publication bias and study heterogeneity. We used mixed-effects logistic regression to explore sex and age interactions. Results The relative risk related to alcohol intake increased from 1.05 (95% confidence interval 1.04 - 1.06) at 20 grams of ethanol per day to 1.6 (1.4 - 1.7) and 6.1 (4.4 - 8.6) at 60 and 120 grams per day, respectively. This relation was not modified by sex or age. The relative risk related to hepatitis B infection was 11.6 (8.3 - 16.3) and did not change after adjusting for country-level alcohol. For hepatitis C infection, the relative risk was 7.4 (4.3 - 12.8) after adjusting for alcohol. Female sex reduced the relative risk of cancer related to hepatitis infection. This relation was significant for hepatitis C only. Conclusions Unbiased relative risk estimates of liver cancer adjusted for major risk factors are essential for quantification of the contribution of each risk factor to liver cancer burden. Our results will help cast public health attention to risk factors with the largest contribution to liver cancer burden.