Previous hepatitis B viral infection–an underestimated cause of pancreatic cancer

BACKGROUND: The etiology of pancreatic cancer remains unclear. This limits the possibility of prevention and effective treatment. Hepatitis B virus (HBV) is responsible for the development of different types of cancer, but its role in pancreatic cancer is still being discussed. AIM: To assess the prevalence of previous HBV infection and to identify viral biomarkers in patients with pancreatic ductal adenocarcinoma (PDAC) to support the role of the virus in etiology of this cancer. METHODS: The data of 130 hepatitis B surface antigen-negative subjects were available for the final analysis, including 60 patients with PDAC confirmed by cytology or histology and 70 sex- and age-matched controls. All the participants were tested for HBV biomarkers in blood [antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA], and for those with PDAC, biomarkers in resected pancreatic tissues were tested (HBV DNA, HBV pregenomic RNA and covalently closed circular DNA). We performed immunohistochemistry staining of pancreatic tissues for hepatitis B virus X antigen and Ki-67 protein. Non-parametric statistics were used for the analysis. RESULTS: Anti-HBc was detected in 18/60 (30%) patients with PDAC and in 9/70 (13%) participants in the control group (P = 0.029). Accordingly, the odds of PDAC in anti-HBc-positive subjects were higher compared to those with no previous HBV infection (odds ratio: 2.905, 95% confidence interval: 1.191-7.084, standard error 0.455). HBV DNA was detected in 8 cases of PDAC and in 6 of them in the pancreatic tumor tissue samples only (all patients were anti-HBc positive). Blood HBV DNA was negative in all subjects of the control group with positive results of the serum anti-HBc test. Among 9 patients with PDAC, 5 revealed signs of replicative competence of the virus (covalently closed circular DNA with or without pregenomic RNA) in the pancreatic tumor tissue samples. Hepatitis B virus X antigen expression and active cell proliferation was revealed by immunohistochemistry in 4 patients with PDAC in the pancreatic tumor tissue samples. CONCLUSION: We found significantly higher risks of PDAC in anti-HBc-positive patients. Detection of viral replication and hepatitis B virus X protein expression in the tumor tissue prove involvement of HBV infection in pancreatic cancer development.