Cholangiocarcinoma Associated with Chronic Hepatitis B

Abstract

Purpose: Cholangiocarcinoma (CCA), a rare malignancy of the biliary duct system, arises from epithelial cells of the intrahepatic or extrahepatic bile ducts. Clinical presentation varies depending on location of tumor, but includes jaundice, pruritus, abdominal pain, weight loss, and fever. Primary sclerosing cholangitis, choledochal cysts, and infection with parasitic liver flukes are risk factors strongly associated with CCA. Hepatitis B virus infection (HBV) is associated with hepatocellular carcinoma, but very rarely with CCA. We present an unusual case of CCA in a patient with chronic HBV infection. Methods: A 38 year old Asian male with chronic untreated HBV infection presented to an outside hospital with fever, fatigue, and right upper quadrant abdominal pain for one week. Imaging studies revealed a right hepatic lobe mass and portal vein thrombosis. Liver biopsy was performed and the patient was referred to our hospital for further management. Physical exam revealed jaundice and hepatomegaly. Hemoglobin was 12.8 g/dl, platelet count 236 × 103/mcL, albumin 3.1 g/dl, bilirubin 0.7 mg/dL, alkaline phosphatase 147 IU/L, aspartate aminotransferase 57 IU/L, alanine aminotransferase 39 IU/L, INR 1.5, alpha-fetoprotein level 114 ng/ml, CA 19-9 of 45 U/ml, and HBV DNA 27,567 IU/ml. Repeat imaging demonstrated a 9.9 × 6.8 cm infiltrating mass extending from the dome inferiorly and invading the gallbladder, as well as portal vein thrombosis. A chest computed tomography (CT) and bone scan were negative for metastatic disease. Liver biopsy of the mass showed moderately differentiated adenocarcinoma and dysplasia of bile ducts. Immunostaining was compatible with CCA. A liver biopsy obtained from the left unaffected lobe revealed HBV hepatitis with early cirrhosis. The patient was not a candidate for liver transplantation. Results: Subsequently, an exploratory laparotomy revealed no obvious peritoneal seeding, thus a right hepatectomy and cholecystectomy were performed. Pathology was consistent with CCA and an abundance of hepatocytes positive for hepatitis B surface antigen. The patient had an uncomplicated postoperative course and was discharged on antiviral HBV medications and follow up with oncology and radiation oncology. Conclusion: We demonstrate a unique, rare case of CCA associated with chronic HBV. It has been proposed that HBV may infect biliary epithelium resulting in an immunologic attack causing inflammation and degenerative changes. More research is needed to evaluate the potential role of HBV in the pathogenesis of CCA, so that we can prevent and control this devastating disease.