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Analysis of the mechanism of liver injury and carcinogenesis in HCV infection

Research Project

Project/Area Number 02404038
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

KAMADA Takenobu  Osaka Univ. Medical School, Professor, 医学部, 教授 (80028399)

Co-Investigator(Kenkyū-buntansha) KATAYAMA Kazuhiro  Osaka Univ. Hospital,Research fellow, 医学部・附属病院, 医員
KASAHARA Akinori  Osaka Univ. Medical School, Assist.Prof., 医学部, 助手 (70214286)
HAYASHI Norio  Osaka Univ. Medical School, Lecturer, 医学部, 講師 (00144478)
佐々木 裕  大阪大学, 医学部, 助手
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥22,800,000 (Direct Cost: ¥22,800,000)
Fiscal Year 1992: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1991: ¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1990: ¥10,200,000 (Direct Cost: ¥10,200,000)
Keywordshapatitis C virus / chronic liver disease / polymerase chain reaction / HCV RNA / Viral replication / Interferon therapy / Immunohistochemical staining / "in situ" hybridization / 慢性肝疾患 / PCR法 / NCV RNA / ウイルス量 / 免疫組織化学 / “in situ"hybridization / C型肝炎 / 非A非B型慢性肝疾患 / 肝癌 / 肝病変 / HCVーRNA / 慢性肝炎
Research Abstract

Since the genome of hepatitis C virus (HCV) was been cloned from experimentally infected chimpanzee plasma, testing for antibody to hepatitis C virus has shown that HCV is the etiological agent for most cases of non-A, non-B (NANB) hepatitis. We evaluated the prevalence of antibody to the core protein of HCV and found that HCV is related with more than 95% of NANB chronic liver disease and that there is a close correlation between the presence of anti-HCV core and HCV carriers. We quantified HCV RNA in serum by the competitive RT-PCR assay to correlate the replicative level of HCV with (1)various stages of the carrier states or (2)a sustained response to interferon (IFN) therapy. The amounts of HCV RNA in serum ranged from 10^4 to 10^<9.5> copies/mL serum. The titer of HCV RNA were lower in asymptomatic blood donors and in patients with chronic persistent hepatitis compared with those having chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The initial titer … More of HCV RNA before IFN therapy of long-term responders were significantly lower than those of short-term responders and non-responders. Multivariate analysis showed that the HCV RNA titer before therapy was the strongest independent predictor of a sustained response to IFN therapy. We determined the localization of the HCV-infected hepatocytes by immunohistochemical studies and "in situ"hybridization technique. Positive staining or signal was found in less than 50% of studied specimens. Hepatocytes with positive results were scattered in the lobules. Intralobular inflammation and fibrosis had higher scores for samples with positive rather than negative results. In liver tissue of patients with HCC, detection of strand-specific HCV RNA by PCR showed that not only positive-strand but also negative-strand could be amplified in both cancerous and non- cancerous liver tissue. These results showed that the replicative level of HCV is higher in advanced liver disease, and that elevation of viral replication might play an important role in liver injury, progression of liver disease and carcinogenesis. Less

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Hagiwara,H.et al.: "Detection of hepatitis C virus RNA in serum of patients with chronic hepatitisC treated with interferon-α" Hepatology. 15. 37-41 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hagiwara H,et al.: "Detection of hepatitis C virus RNA in chronic non-A,non-B liver disease." Gestroenterology. 102. 692-694 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mita E,et al.: "Expression of MBP-HCV NS1/E2 fusion protein in E.coli and detection of anti-NS1/E2 antibody in type C chronic liver disease." Biochem Biophys Res Commum. 183. 925-930 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takehara T,et al.: "Detection of the mines strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction:Implication for HCV replication in infected tissue." Hepatology. 15. 387-390 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiramatsu N,et al.: "Immunohistochemical detection of hepatitis C vires-infected hepatocvtes in chronic liver disease with monoclonal antibodies to core,envelope and NS3 regions of the HCV genome." Hepatology. 16. 306-311 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuki N,et al.: "HCV RNZ and antibody to HCV core protein in Japanese patients with chronic liver disease." Dig Dis Sci. 37. 1483-1488 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takehara T, et al: "Two-dimensional flow cytometric analysis of intrahepatic lymphocyte subsets from patients with chronic hepatitis." Dig Dis Sci. 36. 87-91 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hagiwara H, et al: "Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-alpha." Hepatology. 15. 37-41 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hagiwara H, et al: "Detection of hepatitis C virus RNA in chronic non-A, non-B liver disease." Gastroenterology. 102. 692-694 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuki N, et al: "Hepatitis B virus Markers and antibodies to hepatitis C virus in Japanese patients with hepatocellular carcinoma." Dig Dis Sci. 37. 65-72 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mita E, et al: "Expression of MBP-HCV NS1/E2 fusion protein in E.coli and detection of anti-NS1/E2 antibody in type C chronic liver disease." Biochem Biophys Res Commum. 183. 925-930 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takehara T, et al: "Detection of the minus strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction:Implication for hepatitis C virus replication in infected tissue." Hepatology. 15. 387-390 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hagiwara H,et al: "Three cases of posttransfusion hepatitis C treated with interferon-alpha: confirmation of a carrier state by detection of hepatitis C virus RNA after interferon therapy." Dig Dis Sci. 37. 631-634 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuki N, et al: "Improved serodiagnosis of chronic hepatitis C in Japan by a second-generation enzyme-linked immunosorbent assay." J Med Virol. 37. 237-240 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiramatsu N, et al: "Immunohistochemical detection of hepatitis C virus-infected hepatocytes in chronic liver disease with monoclonal antibodies to core, envelope and NS3 regions of the hepatitis C virus genome." Hepatology. 16. 306-311 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuki N, et al: "Antibodies to a putative hepatitis C virus polyprotein in Japanese patients with chronic liver disease." J Med Virol. 38. 86-91 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuki N, et al: "HCV RNA and antibody to HCV core protein in Japanese patients with chronic liver disease." Dig Dis Sci. 37. 1483-1488 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hagiwara H,et al.: "Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-α." Hepatology. 15. 37-41 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hagiwara H,et al.: "Detection of hepatitis C virus RNA in chronic non-A,non-B liver disease." Gastroenterolgy. 102. 692-694 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mita E,et al.: "Expression of MBP-HCV NS1/E2 fusion protein in E.coli and detection of anti-NS1/E2 antibody antibody in type C chronic liver disease." Biochem Biophys Res Commum. 183. 925-930 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takehara T,et al.: "Detection of the minus strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction:Implication for HCV replication in infected tissue." Hepatology. 15. 387-390 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiramatsu N,et al.: "Immunohistochemical detection of hepatitisC virus-infected hepatocytes in chronic liver disease with monoclonal antibodi to core,envelope and S3 regions the HCV genome." Hepatology. 16. 306-311 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yuki N,et al.: "HCV RAN and antibody to HCV core protein in Japanexe patients with chronic liver disease." Dig Dis Sci. 37. 1483-1488 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yuki N,et al.: "Hepatitis B virus markers and antibodies to bepdtitis C virus in Japanese patients with hepatocellular carcinoma." Dig.Dis.Sci.37. 65-72 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hagiwara H,et al.: "Detection of hepatitis C virus RNA in chronic nonーA,nonーB liver diseacse." Gastroenterology. 102. 692-694 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hagiwara H,et al.: "Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon alpha." Hepatology. 15. 37-41 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takehara T,et al: "Detection of minas strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction" Hepatology. 15. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 結城 暢一,他: "HCV抗体陽性慢性肝疾患におけるHBV関連マ-カ-の検討." 日本消化器病学会雑誌. 87. 2466-2472 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yuki N,et al.: "Detection of antibodies against the polymerase gene product in hepatitis B virus infection." Hepatology. 12. 193-198 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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