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Reactivation of precore mutant hepatitis B virus leading to fulminant hepatic failure following cytotoxic treatment

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Abstract

Three hepatitis B virus carriers who were HBeAg negative and having normal liver function developed fulminant hepatitis with evidence of HBV replication following intensive chemotherapy for non-Hodgkin's lymphoma. Each was continuously negative for HBeAg. Analysis of the precore region of HBV isolated from each demonstrated that the HBV of each had a point mutation in the precore region that inhibited the synthesis and the release of hepatitis Be antigen. This observation suggests that all HB carriers receiving either immunosuppressive or cytotoxic therapy should be monitored closely even if standard assays suggest that viral replication is not present. Sudden enhanced replication of a HBV mutant as a result of such therapy can be a cause of either very severe hepatitis or occasionally fulminant hepatitis.

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References

  1. Sculloard GH, Smith CI, Merigan TL, Robinson WS, Gregory PB: Effects of immunosuppressive therapy on viral markers in chronic active hepatitis B. Gastroenterology 81:987–991, 1981

    Google Scholar 

  2. Rakela J, Redeker AG, Weliky B: Effect of short-term predonisone therapy on aminotransferase levels and hepatitis B virus markers in chronic type B hepatitis. Gastroenterology 84:956–960, 1983

    Google Scholar 

  3. Nair PV, Tong MJ, Stevenson D, Roskamp D, Boone C: A pilot study on the effects of predonisone withdrawal on serum hepatitis B virus, DNA and HBeAg in chronic active hepatitis B. Hepatology 6:1319–1324, 1986

    Google Scholar 

  4. Hess G, Manns M, Hutteroth M, Meyer zum Buschenfeld KM: Discontinuation of immunosuppressive therapy in hepatitis B surface antigen-positive chronic hepatitis: Effect on viral replication and on liver cell damage. Digestion 36:47–54, 1987

    Google Scholar 

  5. Wands JR: Subacute and chronic active hepatitis after withdrawal of chemotherapy. Lancet 2:979, 1975

    Google Scholar 

  6. Wands JR, Chura CM, Roll FJ, Maddrey WC: Serial studies of hepatitis-associated antigen and antibody in patients receiving antitumor chemotherapy for myeloproliferative and lymphoproliferative disorders. Gastroenterology 68:105–112, 1975

    Google Scholar 

  7. Villa E, Theodossi A, Portmann B, Eddleston ALWF, Williams R: Reactivation of hepatitis B virus infection in two patients: Immunofluorescene studies of liver tissue. Gastroenterology 80:1046–1052, 1981

    Google Scholar 

  8. Hoofnagle JH, Dusheiko GM, Schafer DF, Jones EA, Micetich KC, Young RC, Costa J: Reactivation of chronic hepatitis B virus infection by cancer chemotherapy. Ann Intern Med 96:447–449, 1982

    Google Scholar 

  9. Lau JYN, Bird GLA, Gimson AES, Alexander GJ, Williams R: Treatment of HBV reactivation after withdrawal of immunosuppression. Lancet 337:807, 1991

    Google Scholar 

  10. Lok ASF, Liang RHS, Chiu EKW, Wong K-L, Chan T-K, Todd D: Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Gastroenterology 100:182–188, 1991

    Google Scholar 

  11. Grumayer ER, Panzer S, Ferenci P, Gadner H: Recurrence of hepatitis B in children with serologic evidence of past hepatitis B virus infection undergoing antileukemia chemotherapy. J Hepatol 8:232–235, 1989

    Google Scholar 

  12. Galbraith RM, Eddleston ALWF, Williams R, Zuckerman AJ, Bagshawe KD: Fulminant hepatic failure in leukemia and choriocarcinoma related to withdrawal of cytotoxic drug therapy. Lancet 2:528–530, 1975

    Google Scholar 

  13. Thung SN, Gerber MA, Klion F, Gilbert H: Massive hepatic necrosis after chemotherapy withdrawal in a hepatitis B virus carrier. Arch Intern Med 145:1313–1314, 1985

    Google Scholar 

  14. Pariente EA, Goudeau A, Dubois F, Degott C, Gluckman E, Devergie A, Brechot C, Schenmetzler C, Bernuau J: Fulminant hepatitis due to reactivation of chronic hepatitis B virus infection after allogenic bone marrow transplantation. Dig Dis Sci 33:1185–1191, 1988

    Google Scholar 

  15. Onwubalili JK: Fulminant hepatic failure in nephrotic syndrome related to withdrawal of immunosuppressive therapy. Postgrad Med J 64:325–327, 1988

    Google Scholar 

  16. Bird GLA, Smith H, Portmann B, Alexander GJM, Williams R: Acute liver decompensation on withdrawal of tytotoxic chemotherapy and immunosuppressive therapy in hepatitis B carriers. Q J Med 270:895–902, 1989

    Google Scholar 

  17. Lau JYN, Lai CL, Lin HJ, Lok ASF, Liang RHS, Wu PC, Chan TK, Todd D: Fatal reactivation of chronic hepatitis B virus infection following withdrawal of chemotherapy in lymphoma patients. Q J Med 270:911–917, 1989

    Google Scholar 

  18. Webster A, Brenner MK, Prentice HG, Griffiths PD: Fatal hepatitis B reactivation after autologous bone marrow transplantation. Bone Marrow Transplant 4:207–208, 1989

    Google Scholar 

  19. Flowers MA, Heathcote J, Wanless IR, Sherman M, Reynolds WJ, Cameron RG, Levy GA, Inman RD: Fulminant hepatitis as a consequence of reactivation of hepatitis B virus infection after discontinuation of low-dose methotrexate therapy. Ann Intern Med 112:381–382, 1990

    Google Scholar 

  20. Cherqui D, Girardin MFSM, Haioun C, Lauzet JY, Mavier P, Zafrani ES, Franiez PL, Dhumeaux D: Liver transplantation for fulminant hepatitis following chemotherapy for malignant lymphoma. Lancet 335:1400, 1990

    Google Scholar 

  21. Editorial: Chemotherapy and hepatitis B. Lancet 2:1136–1137, 1989

  22. Kaplan PM, Greenman RL, Gerin TL, Purcell RH, Robinson WS: DNA polymerase associated with human hepatitis B antigen. J Virol 12:995–1005, 1973

    Google Scholar 

  23. Scotto JM, Hadchouel M, Hery HCV, Yvart J, Tiollais YP, Brechot C: Detection of hepatitis B virus DNA in serum by a simple spot hybridization technique: Comparison with results for other viral markers. Hepatology 3:279–284, 1983

    Google Scholar 

  24. Okamoto H, Yotsumoto S, Akahane Y, Yamanaka T, Miyazaki Y, Sugai Y, Tsuda F, Tanaka T, Miyasaka Y, Mayumi M: Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. J Virol 64:1298–1231, 1990

    Google Scholar 

  25. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:498–491, 1988

    Google Scholar 

  26. Sanger F, Nicklen S, Coulsen AR: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467, 1977

    Google Scholar 

  27. Okamoto H, Okada S, Sugiyama Y, Tanaka T, Sugai Y, Akahane Y, Machida A, Mishiro S, Yoshizawa Y, Mayumi M: Detection of hepatitis C virus RNA by a two-stage chain reaction with two pairs of primers deduced from the 5′-noncoding region. Jpn J Exp Med 60:251–222, 1990

    Google Scholar 

  28. Opolon P: Significance of middle molecules in the pathogenesis of hepatic encephalopathy.In Advances in Hepatic Encephalopathy and Urea Cycle Diseases. G Kleinberger, P Ferenci, P Riederer, H Thaben (eds). Basel, Karger, 1984, pp 310–313

    Google Scholar 

  29. Yoshiba M, Yamada H, Yoshikawa Y, Fujiwara K, Toda G, Oka H, Sanjo T, Yamazaki Z, Idezuki Y, Inoue N, Sakai Y, Kunitomo T: Hemodiafiltration treatment of deep coma by protein passing membrane; Case report. Artif Organs 10:417–421, 1986

    Google Scholar 

  30. Locasciulli A, Santameria M, Mesera G, Schiavon E, Alberti A, Realdi G: Hepatitis B virus markers in children with acute leukemia: The effect of chemotherapy. J Med Virol 15:29–33, 1985

    Google Scholar 

  31. Hadziyannis SJ, Lieberman HM, Karvountzis CG, Shafriz DA: Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg vs anti-HBe positive carriers of hepatitis B virus. Hepatology 3:656–662, 1983

    Google Scholar 

  32. Bonino F, Rosina F, Rizzeto M, Rizzi R, Chiagberge E, Tardanico R, Callea F, Verme G: Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe. Gastroenterology 90:1268–1273, 1986

    Google Scholar 

  33. Carmen WF, Jacyna MR, Hadziyannis S, Karayiannis P, McGavey MJ, Markis A, Thomas HC: Mutation preventing formation of hepatitis Be antigen in patients with chronic hepatitis B infection. Lancet 2:588–590, 1989

    Google Scholar 

  34. Akahane Y, Yamanaka T, Suzuki H, Sugai Y, Tsuda F, Yotsumoto S, Omi S, Okamoto H, Miyakawa Y, Mayumi M: Chronic active hepatitis with hepatitis B virus DNA and antibody against e antigen in the serum. Gastroenterology 99:1119–1133, 1990

    Google Scholar 

  35. Kosaka Y, Takase K, Kojima M, Shimizu M, Inoue K, Yoshiba M, Tanaka S, Akahane Y, Okamoto H, Tsuda F, Miyakawa Y, Mayumi M: Fulminant hepatitis B; Induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen. Gastroenterology 100:1087–1094, 1991

    Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology, Showa University, Fujigaoka Hospital, Yokohama, Japan

    Makoto Yoshiba, Kazuhiko Sekiyama, Fumio Sugata, Hiroaki Okamoto, Kayoko Yamamoto & Shigeru Yotsumoto

  2. Immunology Division, Jichi Medical School, Tochigi, Japan

    Makoto Yoshiba, Kazuhiko Sekiyama, Fumio Sugata, Hiroaki Okamoto, Kayoko Yamamoto & Shigeru Yotsumoto

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  1. Makoto Yoshiba
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  2. Kazuhiko Sekiyama
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  3. Fumio Sugata
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  4. Hiroaki Okamoto
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  5. Kayoko Yamamoto
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  6. Shigeru Yotsumoto
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Yoshiba, M., Sekiyama, K., Sugata, F. et al. Reactivation of precore mutant hepatitis B virus leading to fulminant hepatic failure following cytotoxic treatment. Digest Dis Sci 37, 1253–1259 (1992). https://doi.org/10.1007/BF01296569

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  • DOI: https://doi.org/10.1007/BF01296569

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