Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma

Abstract

Bile duct cells and hepatocytes differentiate from the same hepatic progenitor cells. To investigate the possible association of viral hepatitis B and C with intrahepatic cholangiocarcinoma (ICC), we conducted a retrospective case -control study using univariate and multivariate logistic analyses to identify risk factors for ICC. Besides hepatic lithiasis (25.6%; Po0.001), seropositivity for hepatitis B surface antigen (37.5% of all ICC patients; odds ratio (OR) ¼ 4.985, Po0.001) and seropositivity for hepatitis C antibodies (13.1%; OR ¼ 2.709; P ¼ 0.021) are the primary independent risk factors for ICC. Cirrhosis exerted synergic effects on the development of ICC. We compared the age distributions of viral-hepatitis associated ICC to that of viral hepatitis-associated hepatocellular carcinoma (HCC). The mean age of ICC patients with viral hepatitis B (56.4 ± 11.1 years) were 9 years younger than that of ICC patients with viral hepatitis C (65.6 ± 9.17 years), similar to that observed in HCC. The incidence ratio of HCC : ICC : CHC (combined hepatocellular cholangiocarcinoma) in our population was 233 : 17 : 1 consistent with the theoretic ratio of hepatocyte number to cholangiocyte number in the liver. Our findings indicated that both viral hepatitis-associated ICC and HCC shared common disease process for carcinogenesis and, possibly, both arose from the hepatic progenitor cells.

Comparison of clinicopathological characteristics between cirrhotic and non-cirrhotic patients with intrahepatic cholangiocarcinoma: A large-scale retrospective study

“…HBV infection and cirrhosis are established risk factors for HCC (8,11), and several recent studies have suggested HBV infection may also be associated with the occurrence of ICC (12,13,18,19); however, the association between cirrhosis and the pathogenesis/prognosis of ICC remains unknown. The present study confirmed the earlier observation that cirrhosis is prevalent among patients with ICC in highly endemic areas (6), as it was observed in 23.0% of our patients, which is a markedly higher percentage compared with Western (26), and 90.1% of cases with cirrhosis in the present series were seropositive for hepatitis B surface antigen, indicating HBV-related cirrhosis.…”

“…A significant proportion of ICC patients are also cirrhotic; however, the prognostic role of this finding has not been extensively investigated. Although HBV infection has been reported to be a favorable prognostic factor for ICC patients and the clinicopathological characteristics differ between patients with and those without HBV infection (13,18,19), the role of cirrhosis in the prognosis of ICC patients has not been fully elucidated due to the limited number of related studies. Cirrhosis has been found to be a favorable prognostic factor for ICC patients in our former study (20); however, the opposite result was reported by another previous study (21).…”

“…Previous studies suggested that hepatitis B virus (HBV) infection and cirrhosis, which are well-documented pathogenic factors in the development of HCC (8)(9)(10)(11), may also be associated with an increased risk of ICC (12)(13)(14)(15). Cirrhosis is common among HCC patients (8)(9)(10), and has been proven to be a poor prognostic factor following surgical treatment of HCC (10,16,17).…”

Viral hepatitis is associated with intrahepatic cholangiocarcinoma with cholangiolar differentiation and N-cadherin expression

“…Recently, several reports have suggested that infection with hepatitis B or C virus is a possible etiological factor for cholangiocarcinoma. 8,9,[16][17][18] Viral hepatitis-associated cholangiocarcinomas have some clinical features in common with hepatocellular carcinoma. They tend to occur at an earlier age, affect men more frequently, are more likely to cause elevated serum a-fetoprotein levels, and less likely to cause elevated serum CA19-9 levels.…”

“…15 In addition, several studies from Japan, Korea, China, and Taiwan indicate that viral hepatitis B and C are statistically related to intrahepatic cholangiocarcinoma. 8,9,[16][17][18] Compared with seronegative intrahepatic cholangiocarcinoma patients, hepatitis B-related intrahepatic cholangiocarcinoma patients tend to be younger and are more frequently male, have higher abnormal aminotransferase and a-fetoprotein levels, and lower abnormal serum carbohydrate antigen 19-9 (CA19-9) levels. 17 Taken together, these findings suggest that hepatitis virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma share common disease processes for carcinogenesis.…”