Special Article
Free Access
Relation of the hepatitis B virus carrier state to hepatocellular carcinoma
Hans Popper M.D., Ph.D.,
David A. Shafritz,
Jay H. Hoofnagle,
Corresponding Author
Hans Popper M.D., Ph.D.
Stratton Laboratory for the Study of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Mount Sinai School of Medicine, New York, New York 10029–6574===Search for more papers by this authorDavid A. Shafritz
Stratton Laboratory for the Study of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Search for more papers by this authorJay H. Hoofnagle
Stratton Laboratory for the Study of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Search for more papers by this authorHans Popper M.D., Ph.D.,
David A. Shafritz,
Jay H. Hoofnagle,
Corresponding Author
Hans Popper M.D., Ph.D.
Stratton Laboratory for the Study of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Mount Sinai School of Medicine, New York, New York 10029–6574===Search for more papers by this authorDavid A. Shafritz
Stratton Laboratory for the Study of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Search for more papers by this authorJay H. Hoofnagle
Stratton Laboratory for the Study of Liver Diseases, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Search for more papers by this author
References
- 1 Hoofnagle JH, Shafritz DA, Popper H. Chronic type B hepatitis and the “healthy” hepatitis B surface antigen carrier state. Hepatology 1987; 7: 758–763.
- 2 World Health Organization. Report of a W.H.O. scientific group (Zuckerman AJ, Chairman). Lancet 1983; 1: 463–465.
- 3 Szmuness W. Hepatocellular carcinoma and the hepatitis B virus: evidence for a causal association. Prog Med Virol 1978; 24: 40–69.
- 4 Cook-Mozafferi P, Van Rensburg S. Cancer of the liver. Br Med Bull 1984; 40: 342–345.
- 5 Hadziyannis S, Gerber MA, Vissoulis C, et al. Cytoplasmic hepatitis B antigen in “ground-glass” hepatocytes of carriers. Arch Pathol 1973; 96: 327–330.
- 6 Knolle J, Born M, Hess G, et al. Die Charakterisierung des klinisch gesunden Hepatitis-B-Antigen-(HBsAg)-Trägers. Klin Wochenschr 1976; 54: 567–578.
- 7 Koretz RL, Lewin KJ, Rebhuhn DJ, et al. Hepatitis B surface antigen carriers—To biopsy or not to biopsy. Gastroenterology 1978; 75: 860–863.
- 8 Dormeyer HH, Arnold W, Schönborn H, et al. Follow-up of anti-HBc titers in healthy HBsAg carriers and patients with chronic inflammatory liver diseases. Digestion 1981; 22: 289–293.
- 9 Dragosics B, Ferenci P, Denk H, et al. Long-term follow-up study of asymptomatic HBsAg-positive voluntary blood donors in Austria: a clinical and histologic evaluation of 242 cases. Hepatology 1987; 7: 302–306.
- 10 Feinman SV, Berris B, Cooter N, et al. Results of a long-term prospective study of the hepatitis B surface antigen (HBsAg) carrier state. Hepato-Gastroenterology 1982; 29: 58–61.
- 11 Shrago SS, Auslander MO, Gitnick GL. Hepatic pathologic condition in asymptomatic Australia antigen carriers. Arch Pathol Lab Med 1977; 101: 648–651.
- 12 Klatskin G. Persistent HB antigenemia: associated clinical manifestations and hepatic lesions. Am J Med Sci 1975; 270: 33–40.
- 13 De Groote J, Gedigk P, Popper H, et al. A classification of chronic hepatitis. Lancet 1968; 2: 626–628.
- 14 Bianchi L, De Groote J, Desmet VJ, et al. Acute and chronic hepatitis revisited. Lancet 1977; 2: 914–919.
- 15 Aldershvile J, Dietrichson O, Skinhøj P, et al. Chronic persistent hepatitis: serological classification and meaning of the hepatitis B e system. Hepatology 1982; 2: 243–246.
- 16 Popper H. Changing concepts of the evolution of chronic hepatitis and the role of piecemeal necrosis. Hepatology 1983; 3: 758–762.
- 17 Cooksley WGE, Bradbear RA, Robinson W, et al. The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis. Hepatology 1986; 6: 345–348.
- 18
Kato Y,
Hirai N,
Hinoue Y, et al.
A clinicopathological study in patients with seroconversions from e antigen to e antibody in HBsAg positive chronic active hepatitis.
Acta Hepatol Jap
1985;
26:
987–992.
10.2957/kanzo.26.987 Google Scholar
- 19 Sheen I-S, Liaw Y-F, Tai D-I, et al. Hepatitis decompensation associated with hepatitis B e antigen clearance in chronic type B hepatitis. Gastroenterology 1985; 89: 732–735.
- 20 Selmair H, Vido I, Wildhirt E, et al. Die chronische nekroti-sierende Hepatitis. Dtsch Med Wochenschr 1970; 95: 1397–1401.
- 21 Chung WK. Study on chronic hepatitis in Korea. In: H Popper, F Schaffner, eds. Progress in liver diseases, Vol VIII. Orlando, Florida: Grune & Stratton, 1986: 469–484.
- 22 Foulds L. Tumor progression. Cancer Res 1957; 17: 355–356.
- 23 Farber E. The multistep nature of cancer development. Cancer Res 1984; 44: 4217–4221.
- 24 Nowell PC. Mechanisms of tumor progression. Cancer Res 1986; 46: 2203–2207.
- 25 Anthony PP, Vogel CL, Barker LF. Liver cell dysplasia: a premalignant condition. J Clin Pathol 1973; 26: 217–223.
- 26
Cohen C,
Berson SD.
Liver cell dysplasia in normal, cirrhotic, and hepatocellular carcinoma patients.
Cancer
1986;
57:
1535–1538.
10.1002/1097-0142(19860415)57:8<1535::AID-CNCR2820570816>3.0.CO;2-8 CAS PubMed Web of Science® Google Scholar
- 27 Stromeyer FW, Ishak KG. Nodular transformation (nodular “regenerative” hyperplasia) of the liver. A clinicopathological study of 30 cases. Human Pathol 1981; 12: 60–71.
- 28 Peters RL. Pathology of hepatocellular carcinoma. In: K Okuda, RL Peters, eds. Hepatocellular carcinoma. New York: John Wiley & Sons, 1976: 107–168.
- 29
Popper H,
Sternberg SS,
Oser BL, et al.
The carcinogenic effect of aramite in rats. A study of hepatic nodules.
Cancer
1960;
13:
1035–1046.
10.1002/1097-0142(196009/10)13:5<1035::AID-CNCR2820130526>3.0.CO;2-X CAS PubMed Web of Science® Google Scholar
- 30 Arakawa M, Kage M, Sugihara S, et al. Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver. Observations in five cases. Gastroenterology 1986; 91: 198–208.
- 31 Ying TS, Sarma DSR, Farber E. Role of acute hepatic necrosis in the induction of early steps in liver carcinogenesis by diethylnitrosamine. Cancer Res 1981; 41: 2096–2102.
- 32
Okuda K,
Peters RL,
Simson IW.
Gross anatomic features of hepatocellular carcinoma from three disparate geographic areas.
Cancer
1984;
54:
2165–2173.
10.1002/1097-0142(19841115)54:10<2165::AID-CNCR2820541017>3.0.CO;2-7 CAS PubMed Web of Science® Google Scholar
- 33 Popper H, Schaffner F. Liver: structure and function. New York: The Blakiston Division, McGraw-Hill Book Company, Inc., 1957: 593–612.
- 34 Kew MC; Popper H. Relationship between hepatocellular carcinoma and cirrhosis. Semin Liver Dis 1984; 4: 136–146.
- 35 Shikata T. Primary liver carcinoma and liver cirrhosis. In: K Okuda, RL Peters, eds. Hepatocellular carcinoma. New York: John Wiley & Sons, 1976: 53–71.
- 36 Popper H, Gerber MA, Thung SN. The relation of hepatocellular carcinoma to infections with hepatitis B and related viruses in man and animals. Hepatology 1982; 2: 1S–9S.
- 37 Shafritz DA, Kew MC. Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas. Hepatology 1981; 1: 1–8.
- 38 Brechot C, Hadchouel M, Scotto J, et al. State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver disease. Proc Natl Acad Sci USA 1981; 78: 3906–3910.
- 39 Shafritz DA, Shouval D, Sherman HI, et al. Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. N Engl J Med 1981; 305: 1067–1073.
- 40 Koshy R, Maupas P, Muller R, et al. Detection of hepatitis B virus-specific DNA in the genomes of human hepatocellular carcinoma and liver cirrhosis tissues. J Gen Virol 1981; 57: 95–102.
- 41 Koch S, von Loringhoven AF, Hofschneider PH, et al. Amplification and rearrangement in hepatoma cell DNA associated with integrated hepatitis B virus DNA. EMBO J 1984; 3: 2185–2189.
- 42 Ziemer M, Garcia P, Shaul Y, et al. Sequence of hepatitis B virus DNA incorporated into the genome of a human hepatoma cell line. J Virol 1985; 53: 885–892.
- 43 Brechot C, Hadchouel M, Scotto J, et al. Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state. Lancet 1981; 2: 765–768.
- 44 Brechot C, Pourcel C, Hadchouel M, et al. State of hepatitis B virus DNA in liver diseases. Hepatology 1982; 2: 27S–35S.
- 45 Chen D-S, Hoyer BH, Nelson J, et al. Detection and properties of hepatitis B viral DNA in liver tissues from patients with hepatocellular carcinoma. Hepatology 1982; 2: 42S–46S.
- 46 Land H, Parada LF, Weinberg RA. Cellular oncogenes and multiple carcinogenesis. Science 1983; 222: 771–778.
- 47 Bishop JM. Viral oncogenes. Cell 1985; 42: 23–28.
- 48 Hayward WS, Neel BG, Astrin SM. Activation of a cellular oncogene by promoter insertion in ALV-induced lymphoid leukosis. Nature 1981; 290: 475–480.
- 49 Payne GS, Bishop JM, Varmus HE. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymph mass. Nature 1982; 295: 209–212.
- 50 Dejean A, Brechot C, Tiollais P, et al. Characterization of integrated hepatitis B viral DNA cloned from a human hepatoma and the hepatoma-derived cell line PLC/PRF/5. Proc Natl Acad Sci USA 1983; 80: 2505–2509.
- 51 Mizusawa H, Taira M, Yaginuma K, et al. Inversely repeating integrated hepatitis B virus DNA and cellular flanking sequences in the human hepatoma-derived cell line huSP. Proc Natl Acad Sci USA 1985; 82: 208–212.
- 52 Koike K, Kobayashi M, Mizusawa H, et al. Rearrangement of the surface antigen gene of hepatitis B virus integrated in the human hepatoma cell lines. Nucl Acids Res 1983; 11: 5391–5402.
- 53 Koshy R, Koch S, van Loringhoven AF, et al. Integration of hepatitis B virus DNA: evidence for integration in the single-stranded gap. Cell 1983; 34: 215–223.
- 54 Rogler CE, Sherman M, Su CY, et al. Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science 1985; 230: 319–322.
- 55 Dejean A, Tiollais P. Integration of hepatitis B virus DNA in hepatocellular carcinoma (Abstract). J Cell Biochem 1986; 10A (Suppl): 182.
- 56 Weinberger C, Hallenberg SM, Rosenfeld MG, et al. Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product. Nature 1985; 318: 670–672.
- 57 Hino O, Shows TB, Rogler CE. Structure and chromosomal localization of HBV integrations from hepatocellular carcinomas. In: Abstracts of Papers Presented at the 1985 Meeting on Molecular Biology of Hepatitis B Virus. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, 1985: 78.
- 58 Koufos A, Hansen MF, Lampkin BC, et al. Loss of alleles at loci on human chromosome 11 during genesis of Wilm's tumor. Nature 1984; 309: 170–172.
- 59 Orkin SH, Goldman DS, Sallan SE. Development of homozygosity for chromosome 11p markers in Wilm's tumor. Nature 1984; 309: 172–174.
- 60 Koufos A, Hansen MF, Copeland NG, et al. Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. Nature 1985; 316: 330–334.
- 61 Shafritz DA, Rogler CE. Molecular characterization of viral forms observed in persistent hepatitis infections, chronic liver disease and hepatocellular carcinoma in woodchucks and humans. In: GN Vyas, JL Dienstag, JH Hoofnagle, eds. Viral hepatitis and liver disease. Orlando, Florida: Grune & Stratton, 1984: 225–243.
- 62 London WT, Blumberg BS. A cellular model of the role of hepatitis B virus in the pathogenesis of primary hepatocellular carcinoma. Hepatology 1982; 2: 10S–14S.
- 63 Summers J. Three recently described animal virus models for human hepatitis B virus. Hepatology 1981; 1: 179–183.
- 64 Gerin JL. The woodchuck (Marmota monax): an animal model of hepatitis B virus-like infection and disease. In: FV Chisari, ed. Advances in hepatitis research. New York: Masson Publishing USA, Inc., 1984: 40–48.
- 65 Popper H, Shih JWK, Gerin JL, et al. Woodchuck hepatitis and hepatocellular carcinoma: correlation of histologic with virologic observations. Hepatology 1981; 1: 91–98.
- 66 Marion PL, Van Davelaar MJ, Knight SS, et al. Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus. Proc Natl Acad Sci USA 1986; 83: 4543–4546.
- 67 Yokosuka O, Omata M, Zhou Y-Z, et al. Duck hepatitis B virus DNA in liver and serum of Chinese ducks: integration of viral DNA in a hepatocellular carcinoma. Proc Natl Acad Sci USA 1985; 82: 5180–5184.
- 68 Tyler GV, Snyder RL, Summers J. Experimental infection of the woodchuck (Marmota monax m.) with woodchuck hepatitis virus. Lab Invest 1986; 55: 51–55.
- 69 Marion PL, Knight SS, Salazar FH, et al. Ground squirrel hepatitis virus infection. Hepatology 1983; 3: 519–527.
- 70 Omata M, Yokosuka O, Imazeki F, et al. Transmission of duck hepatitis B virus from Chinese carrier ducks to Japanese ducklings: a study of viral DNA in serum and tissue. Hepatology 1984; 4: 603–607.
- 71 Popper H, Roth L, Purcell RH, et al. Hepatocarcinogenicity of the woodchuck hepatitis virus. Proc Natl Acad Sci USA 1987; 84: 866–870.
- 72 Ogston CW, Jonak GJ, Rogler CE, et al. Cloning and structural analysis of integrated woodchuck hepatitis virus sequences from hepatocellular carcinomas of woodchucks. Cell 1982; 29: 385–394.
- 73 Rogler CE, Summers J. Cloning and structural analysis of integrated woodchuck hepatitis virus sequences from a chronically infected liver. J Virol 1984; 50: 832–837.
- 74 Sherlock S, Fox RA, Niazi S, et al. Chronic liver diseases and primary liver cancer with hepatitis associated (Australia) antigen in serum. Lancet 1970; 1: 1243–1247.
- 75 Kubo Y, Okuda K, Musha H, et al. Detection of hepatocellular carcinoma during a clinical follow-up of chronic liver disease. Gastroenterology 1978; 74: 578–582.
- 76 Coursaget P, Maupas P, Goudeau A, et al. A case/control study of hepatitis B virus serologic markers in Senagalese patients suffering from primary hepatocellular carcinoma. Prog Med Virol 1981; 27: 49–59.
- 77 Chung WK, Sun HS, Park DH, et al. Primary hepatocellular carcinoma and hepatitis B virus infection in Korea. J Med Virol 1983; 11: 99–104.
- 78 Song E, Dusheiko GM, Bowyer S, et al. Hepatitis B viral replication in Southern African blacks with HBsAg-positive hepatocellular carcinoma (Abstract). Hepatology 1983; 3: 817.
- 79 Karayiannis P, Fowler MJF, Lok ASF, et al. Detection of serum HBV-DNA by molecular hybridization. Correlation with HBeAg/anti-HBe status, racial origin, liver histology and hepatocellular carcinoma. J Hepatol 1985; 1: 99–106.
- 80 Sjogren M, Hoofnagle JH. Immunoglobulin M antibody to hepatitis B core antigen in chronic type B hepatitis. Gastroenterology 1985; 89: 252–258.
- 81 Beasley RP, Hwang L-Y. Epidemiology of hepatocellular carcinoma. In: GN Vyas, JL Dienstag, JH Hoofnagle, eds. Viral hepatitis and liver disease. Orlando, Florida: Grune & Stratton, 1984: 209–224.
- 82 Davis GL, Hoofnagle JH, Waggoner JG. Spontaneous reactivation of chronic type B hepatitis. Gastroenterology 1984; 86: 230–235.
- 83 Davis GL, Hoofnagle, JH. Reactivation of chronic hepatitis B virus infection presenting as acute viral hepatitis. Ann Intern Med 1985; 102: 762–765.
- 84 Dienes HP, Purcell RH, Popper H, et al. Simultaneous infection of chimpanzees with more than one hepatitis virus (Abstract). Hepatology 1981; 1: 506.
- 85 Rizetto M, Canese MG, Gerin JL, et al. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis 1980; 141: 590–602.
- 86 Foutch PG, Carey WD, Tabor E, et al. Concomitant hepatitis B surface antigen and antibody in thirteen patients. Ann Intern Med 1983; 99: 460–463.
- 87 Schiels MT, Taswell HF, Czaja A, et al. Concurrent HBsAg and anti-HBs in acute and chronic hepatitis B (Abstract). Hepatology 1984; 4: 1035.
- 88 Thijs CV, van Bergeijk L, Heijtink RA, et al. A family infected with hepatitis B and with concurrently circulating HBsAg and heterotypic anti-HBs. Hepato-Gastroenterology 1984; 31: 69–71.
- 89 Weissberg JI, Andres LL, Smith CI, et al. Survival in chronic hepatitis B. An analysis of 379 patients. Ann Intern Med 1984; 101: 613–616.
- 90 Hall AJ, Winter PD, Wright R. Mortality of hepatitis B positive blood donors in England and Wales. Lancet 1985; 1: 91–93.
- 91 Liaw Y-F, Tai D-I, Chu C-M, et al. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study. Gastroenterology 1986; 90: 263–267.
- 92 Obata H, Hatashi N, Motoike Y, et al. A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection. Int J Cancer 1980; 25: 741–747.
- 93 Kew MC. The possible etiologic role of the hepatitis-B virus in hepatocellular carcinoma: evidence from Southern Africa. In: FV Chisari, ed. Advances in hepatitis research. New York: Masson Publishing USA, Inc., 1984: 203–215.
- 94 Marinier E, Barrois V, Larouze B, et al. Lack of perinatal transmission of hepatitis B virus infection in Senegal, West Africa. J Pediatr 1985; 106: 843–849.
- 95 Prince AM, Alcabes P. The risk of development of hepatocellular carcinoma in hepatitis B virus carriers in New York. A preliminary estimate using death-records matching. Hepatology 1982; 2: 15S–20S.
- 96 Heyward WL, Lanier AP, McMahon BJ, et al. Early detection of primary hepatocellular carcinoma among persons infected with hepatitis B virus. JAMA 1985; 254: 3052–3054.
- 97 Z-Y Tang (Editor). Subclinical hepatocellular carcinoma. Berlin, West Germany: Springer-Verlag, 1985.
- 98 Scullard GH, Greenberg HB, Smith JL, et al. Antiviral treatment of chronic hepatitis B virus infection: infectious virus cannot be detected in patient serum after permanent response to treatment. Hepatology 1982; 2: 39–49.
- 99 Di Bisceglie AM, Waggoner JG, Hoofnagle JH. Hepatitis B virus DNA in patients with chronic hepatitis B. Gastroenterology 1987 (in press).
- 100 Shafritz DA, Arias IM. The relationship between infectivity of serum from hepatitis B virus carriers, antiviral therapy, and integrated hepatitis B virus DNA. Hepatology 1982; 2: 106–107.
