Influence of Occult Hepatitis B Infection on the Risk of Hepatocellular Carcinoma in HCV-Infected Patients

Abstract

SUMMARY H CC is one of the most common malignant tumors worldwide ranging between 3% and 9% annually. Globally, it is the fifth leading cause of cancer and the third leading cause of cancer death. In Egypt, HCC reports were 4.7% of CLD patients. Hospital-based studies from Egypt have reported an overall increase in the relative frequency of HCC cancers in Egypt from approximately 4% in 1993 to 7.3% in 2003 (Shaker et al., 2013). The primary risk factors for HCC are HBV, HCV, dietary alfatoxin exposure and chronic alcohol consumption. HBV and HCV infection are considered as the major risk factors that contribute to the development of HCC (El Azm et al., 2013). The role of HBV infection in pathogenesis of HCC differs from that of HCV infection; HBV-DNA genome integrates in hepatocellular chromosomes. While HCV exerts its effect, most probably, through production of cirrhosis with severe liver damage. Since co-infection with HCV and HBV has been reported to be associated with an accelerated risk of HCC, the relationship between occult HBV infection and HCV related HCC has been extensively reviewed but remains controversial (Squadrito et al., 2013). Although there are few reliable statistics, a large proportion of HCV-infected patients have a past history of HBV infection, as indicated by serum hepatitis B core antibody (anti-HBc) positivity and hepatitis B surface antigen (HBsAg) negativity. It has been demonstrated that HBV DNA may be present in a latent form even after serum HBsAg becomes negative, which is refer to as occult HBV infection. Anti-HBc is considered as a surrogate marker of such latent carriers (Squadrito et al., 2013). The serological assay for the long-lasting antibody response to the highly immunogenic HBV core antigen (anti-HBc) represents a qualified candidate as a surrogate for DNA amplification, or for increasing overall sensitivity when assessing the risk of occult hepatitis in peripheral blood. The risk of occult hepatitis associated with anti-HBc seropositivity has been demonstrated extensively, and the presence of antibody response to HBc can be considered a sentinel marker of occult HBV infection (Hassan et al., 2011). The present study was designed to assess the indirect but important role of the traditional anti-HBc assay for the identification of subjects previously exposed to HBV in the context of the modern definition of OBI and determine the influence of occult hepatitis B infection on the Risk of Hepatocellular Carcinoma in HCV-infected Patients. This study was conducted at the Gastroenterology and Hepatology Unit, Department of Internal Medicine at Misr University for Science and Technology Teaching Hospital and Ain Shams University Hospital. Sixty Egyptian persons (all are HBs Ag negative) were recruited and were divided as follows: Group I: 20 healthy controls with negative HCV Antibody markers. Group II: 20 patients with compensated cirrhotic chronic hepatitis C. Group III: 20 patients with well-established diagnosis of HCC and positive HCV antibody markers. All participants were subjected to history taking, clinical examination, laboratory investigations, abdominal ultrasono-graphy, and assessment of Anti-HBc antibody (Total Antibodies) and assessment of HBV-DNA PCR for anti-HBc Ab positive patients. This study revealed statistical significant relation between occult HBV infection and liver disease progression as regard cirrhosis, consequent splenomegaly and development of ascites This study revealed also statistical significant relation between occult HBV infection and development of HCC in general in comparison between HCC and non-HCC patients as well as progression and advancement of hepatocellular carcinoma as regard number of hepatic focal lesions, size of largest one and invasion of portal vein (PVT) but its role in the development of HCC in HCV-confected patients was less related with statistical insignificant relation might be due to the risk attributable to HCV alone. This study revealed that the HBc Ab test was a sentinel marker for identification of occult HBV infection. These results strongly point to the indirect but important role of the traditional anti-HBc assay for the identification of subjects previously exposed to HBV in the context of the modern definition of OBI and determine the potential role of occult HBV infection in the pathogenesis of liver cirrhosis and development of HCC.