Abstract
The hepatitis B virus (HBV) gene has been detected in hepatocellular carcinoma (HCC) tissue negative for the hepatitis B surface antigen and positive for the hepatitis C virus (HCV) antibody, but the precise role of the HBV gene in hepatocarcinogenesis has yet to be clarified. We studied the HBV gene in liver tissue several years before the emergence of HCC. Eleven patients diagnosed with HCV-positive chronic liver disease and who developed HCC were assigned to group A. HBV DNA was detected in 8 of the 11 patients (73%). Twenty-five patients, who did not develop HCC, were selected as group B. Six of the group B patients were classified as DNA-positive (24%). The HBV DNA in liver tissue was found to be significantly related to HCC development (P < 0.01). Thus, the presence of the HBV gene in patients with chronic HCV associated-liver injury appears to promote hepatocarcinogenesis, although prospective studies are needed to confirm this result.
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Mitri MSD, Poussin K, Baccarini P, Pontisso P, D'Errico A, Simon N, Grigioni W, Alberti A, Beaugrand M, Pisi E, Brechot C, Paterlini P: HCV-associated liver cancer without cirrhosis. Lancet 345:413-415, 1995
Urashima T, Saigo K, Kobayashi S, Imaseki H, Koide Y, Asano T, Kondo Y, Koike K, Isono K: Identification of hepatitis B virus integration in hepatitis C virus-infected hepatocellular carcinoma tissues. J Hepatol 26:771-778, 1997
Shintani Y, Yotsuyanagi H, Moriya K, Fujie H, Tatsumi T, Takeyama T, Makuuti M, Kimura S, Koike K: The significance of hepatitis B virus DNA detected in hepatocellular carcinoma of patients with hepatitis C. Cancer 88:2478-2486, 2000
Tamori A, Nishiguchi S, Kubo S, Koh N, Moriyama Y, Fujimoto S, Takeda T, Shiomi S, Hirohashi K, Kinoshita H, Otani S, Kuroki T: Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus. Hepatology 29:1429-1434, 1999
Ishak K, Baptista A, Bianchi L, Callea F, Groote J D, Gudat F, Denk H, Desmet V, Korb G, MacSween RMN, Phillips MJ, Portmann BG, Poulsen H, Scheuer PJ, Scmid M, Thaler H: Histological grading and staging of chronic hepatitis. J Hepatol 22:696-699, 1995
Kaneko S, Feinstone SM, Miller RM: Rapid and sensitive method for the detection of serum hepatitis B virus DNA using the polymerase chain reaction technique. J Clin Microbiol 27:1930-1933, 1989
Tsurimoto T, Fujiyama A, Matsubara K: Stable expression and replications of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA. Proc Natl Acad Sci USA 84:444-448, 1987
Brechot C, Degos F, Lugassy C, Thiers V, Zafrani S, Franco D, Bismuth H, Trepo C, Benahamou J-P, Wands J, Isserbacher K, Tiollais P, Berthelot P: Hepatitis B virus DNA in patients with chronic liver disease and negative tests for hepatitis B surface antigen. N Engl J Med 312:270-276, 1985
Patrlini P, Gerkin G, Nakajima E, Terre S, D'Errico A, Grigioni W, Nalpas B, Franco D, Wands J, Kew M, Pisi E, Tiollais P, Brechot C: Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen. N Engl J Med 323:80-85, 1990
Sardo MA, Rodino G, Pernice M, Campo S, Squadrito G, Russo F, Raimond G: Inapparent “wild-type” and “e-minus variant” HBV infection in patients with HCV-related chronic hepatitis. Liver 14:241-244, 1994
Koike K, Kobayashi M, Gondo M, Hayashi I, Osuga T, Takada S: Hepatitis B virus DNA is frequently found in liver biopsy samples from hepatitis C virus-infected chronic hepatitis patients. J Med Virol 54:249-255, 1998
Villa E, Grottola A, Buttafoco P, Trande P, Merighi A, Fratti N, Fratti N, Seium Y, Cioni G, Manetenti F: Evidence for hepatitis B virus infection in patients with chronic hepatitis C with and without serological markers of hepatitis B. Dig Dis Sci 40:8-13, 1995
Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Elena M, Raimond G: Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 341:22-26, 1999
Michalak TI, Pasquinelli C, Guilhot S, Chisari FV: Hepatitis B virus persistence after recovery from acute viral hepatitis. J Clin Invest 93:230-239, 1994
Rehermann B, Ferrari C, Pasquinelli C, Chisari FV: The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nature Med 10:1101-1108, 1996
Yotsuyanagi H, Yasuda K, lino S, Moriya K, Shintani Y, Fujie H, Tsutsumi T, Kimura S, Koike K: Persistent viremia after recovery from self-limited acute hepatitis B. Hepatology 27:1377-1382, 1998
Mason A, Yoffe B, Noonan C, Mearns M, Campbell C, Kellely A, Perrillo RP: Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance. Hepatology 16:36-41, 1992
Loriot M-A, Marecellin P, Walker F, Boyer N, Degott C, Randorianatoavina I, Benhamou J-P, Erlinger S: Persistence of hepatitis B virus DNA in serum and liver form patients with chronic hepatitis B after loss of HBsAg. J Hepatol 27:251-258, 1997
Mason AL, Xu L, Guo L, Kuhns M, Perrillo RP: Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen. Hepatology 27:1736-1742, 1998
Okada S, Sato T, Okusaka T, Ishii H, Ikeda M, Kosakamoto H, Yoshimori M Wakabayashi K: Past exposure to hepatitis B as a risk factor for hepatocellular carcinoma in patients with chronic liver disease. Br J Cancer 77:2028-2031, 1998
Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Tsukamoto T, Hamba H, Shuto T, Yamamoto T, Ikebe T, Kinoshita H: Clinical significance of prior hepatitis B virus infection in patients with hepatitis C virus-related hepatocellular carcinoma. Cancer, 86:793-798, 1999
Shiratori Y, Shiina S, Zang P Y, Ohno E, Okudaira T, Payawal DA, Ono-nita SK, Imamura M, Kato N, Omata M: Does dual infection by hepatitis B viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan? Cancer 80:2060-2067, 1997
Stevens CE, Taylor PE, PinDyck J, Choo QL, Bradley DW, Kuo G, Houghton M: Epidemiology of hepatitis C virus: a preliminary study in volunteer blood donors. JAMA 263:49-53, 1990
Biscegile AM, Order SE, Klein JL, Waggoner JG, Sjogren MH, Kuo G, Houghton M, Choo Q-L, Hoofnagle J: The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Am J Gastroenterol 86:335-338, 1991
Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS, Chan FK, Sung JJ: Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection. Am J Gastroenterol 97:1211-1215, 2002
Kawai S, Yokosuka O, Imazeki F, Maru Y, Saisho H: State of HBV DNA in HBsAg-negative, anti-HCV-positive hepatocellular carcinoma: Existence of HBV DNA possibly as nonintegrated form with analysis by Alu-HBV DNA PCR and conventional HBV PCR. J Med Virol 64:410-418, 2001
Beasley RP, Hwang L-Y, Lin C-C, Chien C-S: Hepatocellular carcinoma and hepatitis B virus. Lancet 21:1129-1133, 1981
Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD: Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59:1145-1156, 1989
Paterlini P, Poussin K, Kew M, Franco D, Brechot C: Selective accumulation of the X transcripts of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma. Hepatology 21:313-321, 1995
Tarao K, Rino Y, Ohkawa S, Shimizu A, Tamai S, Miyakawa K, Aoki H, Imada T, Shindo K, Okamoto N, Totsuka S: Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis. Cancer 86:589-595, 1999
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Fujioka, SI., Shimomura, H., Iwasaki, Y. et al. Hepatitis B Virus Gene in Liver Tissue Promotes Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients. Dig Dis Sci 48, 1920–1924 (2003). https://doi.org/10.1023/A:1026153800896
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DOI: https://doi.org/10.1023/A:1026153800896