The pathobiology of hepatitis C virus (HCV) in the biliary system has not been clarified yet, although bile duct damage is a histological finding characteristic of chronic hepatitis C. In this study, we examined whether HCV infects bile ducts and is released into the bile. Twelve patients positive for serum HCV antibody were examined in this study, and eight were seropositive for HCV RNA by polymerase chain reaction (PCR). For those who underwent abdominal surgery, the bile was aspirated from the gall bladders by fine needle puncture. Five underwent wedge liver biopsy. Series of saline-diluted bile were assayed for HCV RNA by PCR to determine the HCV RNA titers. To examine HCV expression in the biliary system, the liver specimens were immunostained using monoclonal antibodies to the HCV proteins. HCV RNA was detected in the bile of 5 patients with high serum HCV RNA load (>2.5 Meq/mL). Comparison of viral loads between serum and bile revealed that the HCV RNA level in the bile was as high as that in serum. Furthermore, immunohistological study showed that bile duct epithelial cells were infected with HCV. In contrast, HCV was not found in either the bile or bile duct of patients seronegative for HCV RNA or with low serum HCV load (<1.1 Meq/mL). These findings suggest that the biliary system is involved in the pathobiology of HCV and that the bile is as highly infectious as the serum. (HEPATOLOGY 2001;33:977-980.)Many pathologists have pointed out that bile duct damage is a characteristic histopathological finding of chronic hepatitis C. 1,2 Lymphocyte infiltration to periportal areas and damaged bile ducts is usually recognized in livers with chronic hepatitis C virus (HCV) infection. Our previous study suggested that the bile duct damage of HCV-infected patients is closely associated with human leukocyte antigen DR. 3 The bile duct damage may be a result of the host's immunoreaction against HCV-infected bile duct cells. However, the pathobiology of HCV in the biliary system has not been clarified yet.In this study, we focused on the detection of HCV in bile and bile duct cells. We obtained bile by needle aspiration from the gall bladder of HCV-infected patients when they underwent open abdominal surgery. Preliminary trial to detect HCV RNA in bile did not reveal any positive signal in PCR. Therefore, in this study, saline-diluted bile was subjected to PCR to avoid probable inhibition against RNA extraction or PCR procedures by some components of the bile. 4,5 On the other hand, previous immunohistological or in situ hybridization studies for HCV did not detect HCV expression in bile duct. [6][7][8][9][10][11][12] To further examine HCV expression in bile ducts, we used surgical wedge liver biopsy specimens, which contained largersized bile ducts instead of the usual needle biopsy specimens.
PATIENTS AND METHODS
PatientsThe 12 patients studied had serum HCV antibody (ELISA-3, Ortho Diagnostic Systems, NJ) and underwent abdominal surgery. Five patients were female, and seven were male, ranging in age from 48 to 7...