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. 2005 Aug 19;95(7):592–595. doi: 10.1111/j.1349-7006.2004.tb02492.x

Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma

Satoshi Yamamoto 1, Shoji Kubo 1, Seikan Hai 1, Takahiro Uenishi 3, Takatsugu Yamamoto 1, Taichi Shuto 1, Shigekazu Takemura 1, Hiromu Tanaka 1, Osamu Yamazaki 3, Kazuhiro Hirohashi 1, Takashi Tanaka 2
PMCID: PMC11158843  PMID: 15245596

Abstract

Although hepatitis C virus (HCV)‐related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital‐based case‐control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti‐HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotrans‐ferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti‐HCV antibodies (adjusted OR, 6.02; 95% Cl, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan.

E‐mail: m7577175@msic.med.osaka-cu.ac.jp

References

  • 1. Yamamoto M, Takasaki K, Nakano M, Saito A. Minute nodular intrahepatic cholangiocarcinoma. Cancer 1998; 82: 2145–9. [PubMed] [Google Scholar]
  • 2. Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H. Incidence of primary cholangiocel‐luar carcinoma of the liver in Japanese patients with hepatitis C virus‐related cirrhosis. Cancer 2000; 88: 2471–7. [DOI] [PubMed] [Google Scholar]
  • 3. Okuda K, Nakanuma Y, Miyazaki M. Cholangiocarcinoma: Recent progress. Part 1: Epidemiology and etiology. J Gastroenterol Hepatol 2002; 17: 1049–55. [DOI] [PubMed] [Google Scholar]
  • 4. Kubo S, Kinoshita H, Hirohashi K, Hamba H. Hepatolithiasis associated with cholangiocarcinoma. World J Surg 1995; 19: 637–41. [DOI] [PubMed] [Google Scholar]
  • 5. Tomimatsu M, Ishiguro N, Taniai M, Okuda H, Saito A, Obata H, Yamamoto M, Takasaki K, Nakano M. Hepatitis C virus antibody in patients with primary liver cancer(hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular‐cholangiocarcinoma)in Japan. Cancer 1993; 72: 683–8. [DOI] [PubMed] [Google Scholar]
  • 6. Yamanaka N, Okamoto E, Ando T, Oriyama T, Fujimoto J, Furukawa K, Tanaka T, Tanaka W, Nishigami T. Clinicopathologic spectrum of resected extraductal mass‐forming intrahepatic cholangiocarcinoma. Cancer 1995; 76: 2449–56. [DOI] [PubMed] [Google Scholar]
  • 7. Altaee MY, Johnson PJ, Farrant JM, Williams R. Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma. Cancer 1991; 68: 2051–5. [DOI] [PubMed] [Google Scholar]
  • 8. Kuper H, Ye W, Broome U, Romelsjo A, Mucci LA, Ekbom A, Adami HO, Trichopoulos D, Nyren O. The risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism, of cirrhosis. Hepatology 2001; 34: 714–8. [DOI] [PubMed] [Google Scholar]
  • 9. Matsumori A, Matoba Y, Sasayama S. Dilated cardiomyopathy associated with hepatitis C virus infection. Circulation 1995; 92: 2519–25. [DOI] [PubMed] [Google Scholar]
  • 10. Tanaka H, Hiyama T, Okubo Y, Kitada A, Fujimoto I. Primary liver cancer incidence rates related to hepatitis‐C virus infection: a correlational study in Osaka, Japan. Cancer Causes Control 1994; 5: 61–5. [DOI] [PubMed] [Google Scholar]
  • 11. Tanaka H, Tsukuma H, Hori Y, Nakade T, Yamano H, Kinoshita N, Oshima A, Shibata H. The risk of hepatitis C virus infection among blood donors in Osaka, Japan. J Epidemiol 1998; 8: 292–6. [DOI] [PubMed] [Google Scholar]
  • 12. Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J. Risk of liver and other types of cancer in patients with cirrhosis: A nationwide cohort study in Denmark. Hepatology 1998; 28: 921–5. [DOI] [PubMed] [Google Scholar]
  • 13. The Liver Cancer Study Group of Japan. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Ann Surg 1990; 211: 277–87. [PMC free article] [PubMed] [Google Scholar]
  • 14. Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, Ahn YO, Shigemastu T. Hepatitis B and C Virus, clonorchis sinensis for the risk of liver cancer: A case control study in Pusan, Korea. Int J Epidemiol 1996; 25: 933–40. [DOI] [PubMed] [Google Scholar]
  • 15. Uchida T, Shikata T, Tanaka E, Kiyosawa K. Immunoperoxidase staining of hepatitis C virus in formalin‐fixed, paraffin‐embedded needle liver biopsy. Virchows Arch 1994; 424: 465–9. [DOI] [PubMed] [Google Scholar]
  • 16. Fisher HP, Doppl W, Osborn M, Altmannsberger M. Evidence for a hepato‐cellular lineage in a combined hepatocellular‐cholangiocarcinoma of transitional type. Virchows Arch B Cell Pathol Incl Mol Pathol 1988; 56: 71–6. [DOI] [PubMed] [Google Scholar]
  • 17. Hirohashi K, Uenishi T, Kubo S, Yamamoto T, Tanaka H, Shuto T, Kinoshita H. The separate‐lesion type combined hepatocellular carcinoma and cholangiocarcinoma. Hepatogastroenterology 2002; 49: 806–9. [PubMed] [Google Scholar]

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