Hepatitis B virus infection and intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved.

Keywords: Hepatitis B virus, Intrahepatic cholangiocarcinoma, Epidemiology, Etiopathogenesis

Core tip: Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor. Its incidence and mortality is increasing drastically over the past two decades worldwide, though the cause for this rise in incidence is unclear. The etiology and carcinogenesis of ICC remain inconclusive. Recent studies suggest that hepatitis B virus (HBV) infection plays an important etiological role in ICC development. HBV-associated ICC holds many clinicopathological similarities with HBV-associated hepatocellular carcinoma (HCC), and HBV-associated ICC patients may have a better prognosis than ICC patients without HBV infection. HBV-associated ICC and HBV-associated HCC may share a common disease process for carcinogenesis, through a similar long-term inflammatory carcinogenic process, and both possibly arise from hepatic progenitor cells.