Prevalence of occult hepatitis B virus infection and Torque teno virus infection and their association with hepatocellular carcinoma in chronic hepatitis C patients

Abstract Background The role of occult hepatitis B virus (HBV) infection and Torque teno virus (TTV) infection in the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients is still uncertain. Aim The aim of the present study was to investigate the prevalence and significance of OBI and TTV infection, and to examine the genetic diversity of these viruses, in chronic hepatitis C patients with and without HCC. Methods Sera from 151 hepatitis C virus (HCV)-infected patients (49 patients with HCC and 102 without HCC) negative for HBV surface antigen (HBsAg) were tested for the presence of OBI and TTV infection by semi-nested and group-specific multiplex PCR assays, respectively. Nucleotide sequencing of HBV S region was further performed. Results OBI and TTV infection were detected in 5 (3.3%) and 68 (45%) patients, respectively. HBV isolates were classified into genotypes A (4/5, 80%) and D (1/5, 20%), and no HBsAg escape mutation was observed. TTV phylogenetic group 3 was the most prevalent among both HCC and non-HCC patients. OBI and TTV infection were significantly more frequent in patients with HCC than patients without HCC ( p  = 0.003, and p  = 0.009, respectively). Moreover, TTV infection was associated with HCC (OR = 2.23, 95% CI = 1.04–4.80, p  = 0.040), independently of liver cirrhosis. Conclusions A low prevalence of OBI was observed in patients with HCV-related chronic liver disease, and TTV infection was an independent factor associated with the occurrence of HCC. Whether TTV influences the progression of liver disease in chronic hepatitis C patients remains to be elucidated.