Hepatology International

, 3:517

Dual chronic hepatitis B virus and hepatitis C virus infection

REVIEW ARTICLE

Abstract

Dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are common in HBV or HCV endemic areas. However, several clinical and pathogenetic issues remain unresolved. First, clinical and in vitro studies suggest the interactions between two viruses. The dynamics of the interaction in untreated setting versus treated setting and its influence on the long-term outcomes await further studies. A key issue regarding viral interactions is whether modulation of infection occurs in the same dually infected individual hepatocyte of the liver. Clarifying this issue may help to understand the reciprocal interference between HCV and HBV and provide clues for future immunopathogenetic studies. Second, the prevalence and clinical significance of coexisting occult HBV infection in patients with chronic HCV infection need further investigations. Third, combination therapy of peginterferon alfa-2a and ribavirin appears to be just as effective and safe for the treatment of hepatitis B surface antigen (HBsAg)-positive patients chronically infected with active chronic hepatitis C as it is in patients with HCV monoinfection. Nevertheless, one-third of dually infected patients with nondetectable serum HBV DNA-level pretreatment developed HBV reactivation posttreatment. How to prevent and treat this reactivation should be clarified. Furthermore, about 10% of the dually infected patients lost HBsAg. Underlying mechanisms await further investigations. Finally, the optimal treatment strategies for dually infected patients with hepatitis B e antigen-positive chronic hepatitis B should be identified in future clinical trials.

Keywords

Dual infection Hepatitis B virus Hepatitis C virus Interferon Pegylated interferon Ribavirin Sustained virologic response HBsAg clearance 

References

  1. 1.
    Liu CJ, Liou JM, Chen DS, Chen PJ. Natural course and treatment of dual hepatitis B virus and hepatitis C virus infections. J Formos Med Assoc 2005;104:783–791PubMedGoogle Scholar
  2. 2.
    Chen DS, Kuo G, Sung JL, et al. Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: the Taiwan experience. J Infect Dis 1990;162:817–822PubMedGoogle Scholar
  3. 3.
    Liu CJ, Chen PJ, Shau WY, et al. Clinical aspects and outcomes of volunteer blood donors testing positive for hepatitis-C virus infection in Taiwan: a prospective study. Liver Int 2003;23:148–155CrossRefPubMedGoogle Scholar
  4. 4.
    Custer B, Sullivan SD, Hazlet TK, et al. Global epidemiology of hepatitis B virus. J Clin Gastroenterol 2004;38(10 Suppl 3):S158–S168CrossRefPubMedGoogle Scholar
  5. 5.
    Li W, Zhu Y, Hua Z. Exploration on the association between the pattern of HBV markers and infection of HCV among population. Zhonghua Liu Xing Bing Xue Za Zhi 1994;15:212–214PubMedGoogle Scholar
  6. 6.
    Chen X, Xuan M, Wu D. Study of super-infection of HBV and HCV. Zhonghua Liu Xing Bing Xue Za Zhi 1999;20:141–143PubMedGoogle Scholar
  7. 7.
    Gaeta GB, Stornaiuolo G, Precone DF, et al. Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. J Hepatol 2003;39:1036–1041CrossRefPubMedGoogle Scholar
  8. 8.
    D’Amelio R, Matricardi PM, Biselli R, et al. Changing epidemiology of hepatitis B in Italy: public health implications. Am J Epidemiol 1992;135:1012–1018PubMedGoogle Scholar
  9. 9.
    Pramoolsinsap C, Sirikulchayanonta V, Busakorn W, et al. Coinfections with hepatitis G and/or C virus in hepatitis B-related chronic liver disease. Southeast Asian J Trop Med Public Health 1999;30:741–749PubMedGoogle Scholar
  10. 10.
    Shiratori Y, Shiina S, Zhang PY, et al. Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan? Cancer 1997;80:2060–2067CrossRefPubMedGoogle Scholar
  11. 11.
    Crespo J, Lozano JL, de la Cruz F, et al. Prevalence and significance of hepatitis C viremia in chronic active hepatitis B. Am J Gastroenterol 1994;89:1147–1151PubMedGoogle Scholar
  12. 12.
    Treitinger A, Spada C, Ferreira LA, et al. Hepatitis B and hepatitis C prevalence among blood donors and HIV-1 infected patients in Florianopolis—Brazil. Braz J Infect Dis 2000;4:192–196PubMedGoogle Scholar
  13. 13.
    Xess A, Kumar M, Minz S, et al. Prevalence of hepatitis B and hepatitis C virus coinfection in chronic liver disease. Indian J Pathol Microbiol 2001;44:253–255PubMedGoogle Scholar
  14. 14.
    Kaur S, Rybicki L, Bacon BR, et al. Performance characteristics and results of a large-scale screening program for viral hepatitis and risk factors associated with exposure to viral hepatitis B and C: results of the National Hepatitis Screening Survey. National Hepatitis Surveillance Group. Hepatology 1996;24:979–986PubMedGoogle Scholar
  15. 15.
    Frank C, Mohamed MK, Strickland GT, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 2000;355:887–891CrossRefPubMedGoogle Scholar
  16. 16.
    el-Sayed HF, Abaza SM, Mehanna S, et al. The prevalence of hepatitis B and C infections among immigrants to a newly reclaimed area endemic for Schistosoma mansoni in Sinai, Egypt. Acta Trop 1997;68:229–237CrossRefPubMedGoogle Scholar
  17. 17.
    Sagnelli E, Coppola N, Messina V, et al. HBV superinfection in hepatitis C virus chronic carriers, viral interaction, and clinical course. Hepatology 2002;36:1285–12891CrossRefPubMedGoogle Scholar
  18. 18.
    Liaw YF, Chen YC, Sheen IS, Chien RN, Yeh CT, Chu CM. Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. Gastroenterology 2004;126:1024–1029CrossRefPubMedGoogle Scholar
  19. 19.
    Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer 1998;75:347–354CrossRefPubMedGoogle Scholar
  20. 20.
    Potthoff A, Deterding K, Trautwein C, Rifai K, Manns MP, Wedemeyer H. Sustained HCV-RNA response and hepatitis Bs seroconversion after individualized antiviral therapy with pegylated interferon alpha plus ribavirin and active vaccination in a hepatitis C virus/hepatitis B virus-co-infected patient. Eur J Gastroenterol Hepatol 2007;19:906–909CrossRefPubMedGoogle Scholar
  21. 21.
    Liu CJ, Chuang WL, Lee CM, et al. Peginterferon alfa-2a plus ribavirin for the treatment of dual chronic infection with hepatitis B and C viruses. Gastroenterology 2009;136:496–504CrossRefPubMedGoogle Scholar
  22. 22.
    Gordon SC, Sherman KE. Treatment of HBV/HCV coinfection: releasing the enemy within. Gastroenterology 2009;136:393–396CrossRefPubMedGoogle Scholar
  23. 23.
    Brotman B, Prince AM, Huima T, Richardson L, van den Ende MC, Pfeifer U. Interference between non-A, non-B and hepatitis B virus infection in chimpanzees. J Med Virol 1983;11:191–205CrossRefPubMedGoogle Scholar
  24. 24.
    Fattovich G, Tagger A, Brollo L, et al. Hepatitis C virus infection in chronic hepatitis B virus carriers. J Infect Dis 1991;163:400–402PubMedGoogle Scholar
  25. 25.
    Sato S, Fujiyama S, Tanaka M, et al. Co-infection of hepatitis C virus in patients with chronic hepatitis B infection. J Hepatol 1994;21:159–166CrossRefPubMedGoogle Scholar
  26. 26.
    Sheen IS, Liaw YF, Chu CM, Pao CC. Role of hepatitis C virus infection in spontaneous hepatitis B surface antigen clearance during chronic hepatitis B virus infection. J Infect Dis 1992;165:831–834PubMedGoogle Scholar
  27. 27.
    Chu CM, Yeh CT, Liaw YF. Low-level viremia and intracellular expression of hepatitis B surface antigen (HBsAg) in HBsAg carriers with concurrent hepatitis C virus infection. J Clin Microbiol 1998;36:2084–2086PubMedGoogle Scholar
  28. 28.
    Jardi R, Rodriguez F, Buti M, et al. Rule of hepatitis B, C and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference. Hepatology 2001;34:404–410CrossRefPubMedGoogle Scholar
  29. 29.
    Liaw YF. Hepatitis C virus super-infection in patients with chronic hepatitis B virus infection. J Gastroenterol 2002;37(Suppl 13):65–68CrossRefPubMedGoogle Scholar
  30. 30.
    Liaw YF, Lin SM, Sheen IS, Chu CM. Acute hepatitis C virus super-infection followed by spontaneous HBeAg seroconversion and HBsAg elimination. Infection 1991;19:250–251CrossRefPubMedGoogle Scholar
  31. 31.
    Shih CM, Lo SJ, Miyamura T, Chen SY, Lee YH. Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol 1993;67:5823–5832PubMedGoogle Scholar
  32. 32.
    Shih CM, Chen CM, Chen SY, Lee YH. Modulation of the transsuppression activity of hepatitis C virus core protein by phosphorylation. J Virol 1995;69:1160–1171PubMedGoogle Scholar
  33. 33.
    Schuttler CG, Fiedler N, Schmidt K, Repp R, Gerlich WH, Schaefer S. Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein. J Hepatol 2002;37:855–862CrossRefPubMedGoogle Scholar
  34. 34.
    Chen SY, Kao CF, Chen CM, et al. Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. J Biol Chem 2003;278:591–607CrossRefPubMedGoogle Scholar
  35. 35.
    Pasquinelli C, Shoenberger JM, Chung J, et al. Hepatitis C virus core and E2 protein expression in transgenic mice. Hepatology 1997;25:719–727CrossRefPubMedGoogle Scholar
  36. 36.
    Pan Y, Wei W, Kang L, et al. NS5A protein of HCV enhances HBV replication and resistance to interferon response. Biochem Biophys Res Commun 2007;359:70–75CrossRefPubMedGoogle Scholar
  37. 37.
    Guo H, Zhou T, Jiang D, et al. Regulation of hepatitis B virus replication by the phosphatidylinositol 3-kinase akt signal transduction pathway. J Virol 2007;81:10072–10080CrossRefPubMedGoogle Scholar
  38. 38.
    Zarski JP, Bohn B, Bastie A, et al. Characteristic of patients with dual infection by hepatitis B and C viruses. J Hepatol 1998;28:27–33CrossRefPubMedGoogle Scholar
  39. 39.
    Ohkawa K, Hayashi N, Yuki N, et al. Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis B patients. J Hepatol 1994;21:509–514CrossRefPubMedGoogle Scholar
  40. 40.
    Ohkawa K, Hayashi N, Yuki N, et al. Long-term follow up of hepatitis B virus and hepatitis C virus replicative levels in chronic hepatitis patients co-infected with both viruses. J Med Virol 1995;46:258–264CrossRefPubMedGoogle Scholar
  41. 41.
    Pontisso P, Gerotto M, Ruvoletto MG, et al. Hepatitis C genotypes in patients with dual hepatitis B and C virus infection. J Med Virol 1996;48:157–160CrossRefPubMedGoogle Scholar
  42. 42.
    Bellecave P, Gouttenoire J, Gajer M, et al. Hepatitis B and C virus coinfection: a novel model system reveals the absence of direct viral interference. Hepatology 2009;50:46–55CrossRefPubMedGoogle Scholar
  43. 43.
    Raimondo G, Brunetto MR, Pontisso P, et al. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-co-infected patients. Hepatology 2006;43:100–107CrossRefPubMedGoogle Scholar
  44. 44.
    Wieland SF, Chisari FV. Stealth and cunning: hepatitis B and hepatitis C viruses. J Virol 2005;79:9369–9380CrossRefPubMedGoogle Scholar
  45. 45.
    Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008;49:652–657CrossRefPubMedGoogle Scholar
  46. 46.
    Li L, Chen PJ, Chen MH, et al. A pilot study for screening blood donors in Taiwan by nucleic acid amplification technology: detecting occult hepatitis B virus infections and closing the serologic window period for hepatitis C virus. Transfusion 2008;48:1198–1206CrossRefPubMedGoogle Scholar
  47. 47.
    Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med 1999;341:22–26CrossRefPubMedGoogle Scholar
  48. 48.
    Fukuda R, Ishimura N, Hamamoto S, et al. Co-infection by serologically silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver. J Med Virol 2001;63:220–227CrossRefPubMedGoogle Scholar
  49. 49.
    Sagnelli E, Copolla N, Colastico C, et al. HCV genotype and “silent” HBV infection: two main risk factors for a more severe liver disease. J Med Virol 2001;64:350–355CrossRefPubMedGoogle Scholar
  50. 50.
    Paterlini P, Driss F, Nalpas B, et al. Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg-negative patients: a study of a low-endemic area. Hepatology 1993;17:20–29CrossRefPubMedGoogle Scholar
  51. 51.
    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 1998;54:249–255CrossRefPubMedGoogle Scholar
  52. 52.
    De Maria N, Colantoni A, Friedlander L, et al. The impact of previous HBV infection on the course of chronic hepatitis C. Am J Gastroenterol 2000;95:3529–3536CrossRefPubMedGoogle Scholar
  53. 53.
    Pollicino T, Squadrito G, Cerenzia G, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology 2004;126:102–110CrossRefPubMedGoogle Scholar
  54. 54.
    Zeuzem S, Feinman SV, Rasenack J, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000;343:1666–1672CrossRefPubMedGoogle Scholar
  55. 55.
    Lee SD, Yu ML, Cheng PN, et al. Comparison of a 6-month course peginterferon alfa-2b plus ribavirin and interferon alfa-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan. J Viral Hepat 2005;12:283–291CrossRefPubMedGoogle Scholar
  56. 56.
    Yu ML, Dai CY, Huang JF, et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology 2008;47:1884–1893CrossRefPubMedGoogle Scholar
  57. 57.
    Villa E, Grottola A, Buttafoco P, et al. High doses of alpha-interferon are required in chronic hepatitis due to coinfection with hepatitis B virus and hepatitis C virus: long term results of a prospective randomized trial. Am J Gastroenterol 2001;96:2973–2977PubMedGoogle Scholar
  58. 58.
    Liu CJ, Chen PJ, Lai MY, Kao JH, Jeng YM, Chen DS. Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients. Hepatology 2003;37:568–576CrossRefPubMedGoogle Scholar
  59. 59.
    Chuang WL, Dai CY, Chang WY, et al. Viral interaction and responses in chronic hepatitis C and B coinfected patients with interferon-alpha plus ribavirin combination therapy. Antivir Ther 2005;10:125–133PubMedGoogle Scholar
  60. 60.
    Hung CH, Lee CM, Lu SN, et al. Combination therapy with interferon-alpha and ribavirin in patients with dual hepatitis B and hepatitis C virus infection. J Gastroenterol Hepatol 2005;20:727–732CrossRefPubMedGoogle Scholar
  61. 61.
    Liu CJ, Chen PJ, Chen DS. A forgotten population with chronic hepatitis C infection: subjects coinfected with hepatitis B virus. Hepatology. 2004;40:266CrossRefPubMedGoogle Scholar
  62. 62.
    Asian Pacific Association for the Study of the Liver (APASL). Hepatitis C Working Party. Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection. J Gastroenterol Hepatol 2007;22:615–633PubMedGoogle Scholar
  63. 63.
    Scott JD, Gretch DR. Molecular diagnostics of hepatitis C virus infection: a systematic review. JAMA 2007;297:724–732CrossRefPubMedGoogle Scholar
  64. 64.
    Marrone A, Zampino R, D’Onofrio M, Ricciotti R, Ruggiero G, Utili R. Combined interferon plus lamivudine treatment in young patients with dual HBV (HBeAg positive) and HCV chronic infection. J Hepatol 2004;41:1064–1065CrossRefPubMedGoogle Scholar
  65. 65.
    Gehenot M, Marcellin P, Colin JF, Martinot M, Benhamou JP, Erlinger S. Alpha interferon therapy in HBsAg positive patients with chronic hepatitis C. Hepatology 1995;22:116AGoogle Scholar
  66. 66.
    Liaw YF, Chien RN, Lin SM, et al. Response of patients with dual hepatitis B virus and C virus infection to interferon therapy. J Interferon Cytokine Res 1997;17:449–452CrossRefPubMedGoogle Scholar
  67. 67.
    Guptan RC, Thakur V, Raina V, Sarin SK. Alpha-interferon therapy in chronic hepatitis due to active dual infection with hepatitis B and C viruses. J Gastroenterol Hepatol 1999;14:893–898CrossRefPubMedGoogle Scholar
  68. 68.
    Utili R, Zampino R, Bellopede P, et al. Dual or single hepatitis B and C virus infections in childhood cancer survivors: long-term follow-up and effect of interferon treatment. Blood 1999;94:4046–4052PubMedGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2009

Authors and Affiliations

  1. 1.Department of Internal Medicine, Graduate Institute of Clinical Medicine, Hepatitis Research CenterNational Taiwan University College of Medicine and National Taiwan University HospitalTaipeiTaiwan

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