Both hepatitis A and hepatitis D infections may be associated with more advanced liver disease in patients with chronic hepatitis B

Acute infection of hepatitis A virus (HAV) causes transient but varying degrees of liver damage. In contrast, hepatitis D virus (HDV) only infects patients with chronic hepatitis B virus (HBV) infection, which may cause chronic and persistent liver damage. We aimed to explore whether infection of both hepatotropic viruses was associated with worse outcomes in patients with chronic HBV infection in a case-control study. We collected serum and clinical data from 456 patients with chronic HBV infection, including 160, 150, and 146 patients with hepatocellular carcinoma (HCC), cirrhosis and inactive carrier status, respectively. Serum HAV-IgG and anti-HDV were determined retrospectively and seroprevalence rates of both markers were compared among the groups with different clinical stages. In the inactive carrier group, 101 (69.18%) and 3 (2.05%) patients had exposure to HAV and HDV infection, respectively. We found higher seropositive rates of HAV-IgG in cirrhosis (82.67%) and HCC (99.38%) groups, but not seropositive rates of anti-HDV (4.67% and 3.75% for cirrhosis and HCC respectively). When combining cirrhosis and HCC groups as patients with advanced liver disease, both seropositive HAV-IgG and anti-HDV were associated with increased risks of advanced liver disease with odds ratio of 10.65 (95% CI [confidence interval]: 2.74-41.41,P < .001) and 12.64 (95% CI: 2.14-74.78,P= .005), respectively. In the case-control study of patients with chronic HBV infection, both exposure to HAV or HDV infection might be associated with increased risks of cirrhosis and HCC development.