Interaction between hepatitis B, hepatitis C and smoking in the development of hepatocellular carcinoma: a systematic review and meta-analysis

Background This meta-analysis reports the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), smoking and their combined impact on the development of hepatocellular carcinoma (HCC).Methods We conducted a systematic search of PubMed, Web of Science and Scopus databases up to 15 July 2023. Observational studies investigating the association between HBV, HCV and smoking in the development of HCC were included. We assessed between-study heterogeneity using the I2 statistics. The effect sizes were estimated as odds ratio (OR) with 95% confidence intervals (CIs) using a random-effects model.Results Out of 20 794 studies identified in the initial search, 32 observational studies involving 22 282 participants met the inclusion criteria. Our meta-analysis showed that the combined impact of HBV and smoking was associated with an OR of 19.81 (95% CI: 14.77, 26.58), HCV and smoking was associated with an OR of 24.86 (95% CI: 12.41, 49.79), and coinfection of HBV and HCV was associated with an OR of 32.58 (95% CI: 20.57, 51.60).Conclusions Our findings indicate a significant interaction between HBV, HCV and smoking in the development of HCC and highlight the importance of addressing smoking cessation and viral hepatitis prevention and treatment as potential strategies for reducing HCC.