Hepatitis D virus dual infection increased the risk of hepatocellular carcinoma compared with hepatitis B virus mono infection: A meta-analysis

Background: Hepatitis delta virus (HDV) is a defective virus that relies on the supply of hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV) to assemble HDV virions and infect hepatocytes. However, controversy remains in whether the presence of HDV increases the risk of hepatocellular carcinoma (HCC). Our aim is to evaluate the influence of HDV on the risk of HCC through a systematic review and meta-analysis. Methods: A review of all English-language literature was conducted in the major medical databases using the subject search terms "hepatocellular carcinoma," "liver cancer," "hepatic tumor," and "hepatitis delta." A meta-analysis of the qualifying publications was then performed. Results: The meta-analysis included 21 studies, which revealed a significantly higher risk of HCC among patients with HDV/HBV dual infection (odds ratio [OR]=2.08, 95% confidence interval [CI], 1.37-3.14, p<0.01) compared with those with HBV monoinfection. Those with HDV/HBV dual infection remained at higher risk of HCC in the subgroup analysis, irrespective of the status of hepatitis C virus (HCV) or human immunodeficiency virus (HIV) coinfection and in different ethnicities. The HCC risk remained higher in patients with HDV/HBV dual infection with heterogeneous fibrosis stage (OR=2.04, 95% CI, 1.31-3.17, p<0.01). The difference in the risk of HCC between HDV/HBV dual infection and HBV monoinfection was not statistically significant in patients with cirrhosis or advanced fibrosis (OR=1.84, 95% CI, 0.48-7.02, p=0.37). However, this subgroup comprised only two studies. Conclusion: HDV and HBV dual infection significantly increase the risk of HCC development compared with HBV monoinfection.