Skip to main content

Advertisement

SpringerLink
Log in

Management and Treatment of Chronic HBV and HCV Co-Infection and the Impact of Anti-Viral Therapy

  • Hepatitis B (J Lim, Section Editor)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Recent reports have demonstrated that chronic hepatitis B virus (HBV) can flare or reactivate when chronic hepatitis C virus (HCV) is treated with direct-acting anti-viral agents (DAAs). Understanding HBV and HCV co-infection is therefore important.

Recent Findings

Although 40–60% of patients with chronic HCV have been previously exposed to HBV; only about 1–6% has serologic evidence of co-infection. In some patients with co-infection, both HBsurface antigen and HBV DNA may be suppressed to undetectable levels by HCV. Complete serologic screening for HBV should be performed in all patients prior to initiating HCV treatment. Patients with HB surface antigen and isolated anti-HBcore require frequent monitoring during HCV treatment, and some will require treatment.

Summary

The epidemiology of HBV, HCV, and co-infection; how these viruses interact within the host; the treatments for each virus; the risk of HBV flare during HCV treatment; and how patients with HBV should be managed during HCV treatment will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis. 2010;14:1–21.

    Article  PubMed  Google Scholar 

  2. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107.

    Article  CAS  PubMed  Google Scholar 

  3. Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56:422–33.

    Article  PubMed  Google Scholar 

  4. Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol. 2011;26(Suppl 1):123–30.

    Article  PubMed  Google Scholar 

  5. Chu CJ, Keeffe EB, Han SH, Perrillo RP, Min AD, Soldevila-Pico C, et al. Hepatitis B virus genotypes in the United States: results of a nationwide study. Gastroenterology. 2003;125:444–51.

    Article  PubMed  Google Scholar 

  6. Lavanchy D. The global burden of hepatitis C. Liver Int. 2009;29(Suppl 1):74–81.

    Article  PubMed  Google Scholar 

  7. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–14.

    Article  PubMed  Google Scholar 

  8. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13:2436–41.

    Article  PubMed  PubMed Central  Google Scholar 

  9. • Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374:2324–34. Randomized clinical trial demonstrating that treatment of patients with high HBV DNA during pregnancy can prevent vertical transmission

    Article  CAS  PubMed  Google Scholar 

  10. Basnayake SK, Easterbrook PJ. Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature. J Viral Hepat. 2016;23:545–59.

    Article  CAS  PubMed  Google Scholar 

  11. Cheruvu S, Marks K, Talal AH. Understanding the pathogenesis and management of hepatitis B/HIV and hepatitis B/hepatitis C virus coinfection. Clin Liver Dis. 2007;11:917–43.

    Article  PubMed  Google Scholar 

  12. Tyson GI, Kramer JR, Duan Z, Davila JR, Richardson PA, El-Serag HB. Prevalence and predictors of hepatits B coinfection in a United States cohort of hepatitis C infected patients. Hepatology. 2013;58:538–45.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bini EJ, Perumalswami PV. Hepatitis B virus infection among America patients with chronic hepatitis C virus infection; prevalence, racial ethnic differences, and viral interaction. Hepatology. 2013;51:759–66.

    Google Scholar 

  14. Liaw YF. Role of hepatitis C virus in dual and triple hepatitis virus infection. Hepatology. 1995;22:1101–8.

    CAS  PubMed  Google Scholar 

  15. Zhang Q, Qi W, Wang X, Zhang Y, Xu Y, Qin S, et al. Epidemiology of hepatitis B and hepatitis C infections and benefits of programs for hepatitis prevention in northeastern China: a cross-sectional study. Clin Infect Dis. 2016;62:305–12.

    Article  PubMed  Google Scholar 

  16. Crockett SD, Keeffe EB. Natural history and treatment of hepatitis B and hepatitis C virus co-infection. Ann Clin Microbiol Antimicrob. 2005;4:13.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Konstantinou D, Deutsch M. The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viral interactions and management. Ann Gastroenterol. 2015;28:221–8.

    PubMed  PubMed Central  Google Scholar 

  18. Zampino R, Pisaturo MA, Cirillo G. Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration. Ann Hepatol. 2015;14:75–82.

    PubMed  Google Scholar 

  19. Crespo J, Lozano JL, de la Cruz F, Rodrigo L, Rodríguez M, San Miguel G, et al. Prevalence and significance of hepatitis C viremia in chronic active hepatitis B. Am J Gastroenterol. 1994;89:1147–51.

    CAS  PubMed  Google Scholar 

  20. Shi J, Zhu L, Liu S, Xie WF. A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer. 2005;92:607–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wiegand SB, Jaroszewicz J, Pothoff A. Dominance of hepatitis C (HCV) virus is associated with lower quantitative hepatitis B surface antigen and higher serum interferon γ induced protein 10 levels in HBV/HCV coinfected patients. Clin Microbiol Infect. 2015;21:710e1–9.

    Article  Google Scholar 

  22. Raimondo G, Brunetto MR, Pontisso P, Smedile A, Maina AM, Saitta C, et al. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-coinfected patients. Hepatology. 2006;43:100–7.

    Article  PubMed  Google Scholar 

  23. Pontisso P, Ruvoletto MG, Fattovich G, Chemello L, Gallorini A, Ruol A, et al. Clinical and virological profiles in patients with multiple hepatitis virus infections. Gastroenterology. 1993;105:1529–33.

    Article  CAS  PubMed  Google Scholar 

  24. Saitta C, Pontisso P, Brunetto MR, Fargion S, Gaeta GB, Niro GA, et al. Virological profiles in hepatitis B virus/hepatitis C virus coinfected patients under interferon plus ribavirin therapy. Antivir Ther. 2006;11:931–4.

    CAS  PubMed  Google Scholar 

  25. Agrawal A, Samrat SK, Arawal B. Co-incubation and core proteins of HBV and HCV leads to modulation of human dendritic cells. Viral Immunol. 2014;27:412–4.

    Article  CAS  PubMed  Google Scholar 

  26. Chen SY, Kao CF, Chen CM, Shih CM, Hsu MJ, Chao CH, et al. Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein. J Biol Chem. 2003;278:591–607.

    Article  CAS  PubMed  Google Scholar 

  27. 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;67:5823–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. • Bersoff-Matcha SJ, Cao K, Jason M, Ajao A, Jones SC, Meyer T, Brinker A. Hepatitis B virus reactivation associated with direct-acting antiviral therapy for chronic hepatitis C virus: a review of cases reported to the U.S. Food and Drug Administration Adverse Event Reporting System. Ann Intern Med. 2017; (in press). Case series complied by FDA demonstrating the impact of HBV reaction during HCV treatment.

  29. Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Galimany R, et al. Role 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;34:404–10.

    Article  CAS  PubMed  Google Scholar 

  30. Liaw YF, Chu CM, Su IJ, Huang MJ, Lin DY, Chang-Chien CS. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology. 1983;84:216–9.

    CAS  PubMed  Google Scholar 

  31. Goldstein ST, Alter MJ, Williams IT, Moyer LA, Judson FN, Mottram K, et al. Incidence and risk factors for acute hepatitis B in the United States, 1982–1998: implications for vaccination programs. J Infect Dis. 2002;185:713–9.

    Article  PubMed  Google Scholar 

  32. Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000;31:777–82.

    Article  CAS  PubMed  Google Scholar 

  33. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW. Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention. Ann Intern Med. 2012;157:817–22.

    Article  PubMed  Google Scholar 

  34. Moyer VA. Screening for hepatitis C infection in adults. US preventative services task force recommendation statement. Ann Intern Med. 2013;159:349–57.

    Article  PubMed  Google Scholar 

  35. Ward JW. The epidemiology of chronic hepatitis C and one-time hepatitis C virus testing of persons born during 1945 to 1965 in the United States. Clin Liver Dis. 2013;17:1–11.

    Article  CAS  PubMed  Google Scholar 

  36. Shiffman ML. Management of acute hepatitis B. Clin Liver Dis. 2010;14:75–91.

    Article  PubMed  Google Scholar 

  37. • Yeh ML, Huang CF, Hsieh MH, Ko YM, Chen KY, Liu TW, et al. Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals. J Gastroenterol Hepatol. 2017; (in press). Prospective study evaluating HBV reactivation in patients with co-infection during HCV treatment.

  38. •• Belperio PS, Shahoumian TA, Mole LA, Backus LI. Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral Hepatitis C antivirals. Hepatology 2017; (in press). The largest retrospective analysis of patients with HCV and HBV co-infection and the impact of HCV treatment.

  39. • Kawagishi N, Suda G, Onozawa M, Kimura M, Maehara O, Ito J, et al. Hepatitis B virus reactivation during hepatitis C direct-acting antiviral therapy in patients with previous HBV infection. J Hepatol. 2017; (in press). Retrospective evaluation of HBV reactivation in patients with co-infection during HCV treatment.

  40. • Wang C, Ji D, Chen J, Shao Q, Li B, Liu J, et al. Hepatitis due to reactivation of hepatitis B virus in endemic areas among patients with hepatitis C treated with direct-acting antiviral agents. Clin Gastroenterol Hepatol. 2017;15:132–6. Observational study Prospective of HBV reactivation in patients with co-infection during HCV treatment

    Article  PubMed  Google Scholar 

  41. • Londoño MC, Lens S, Mariño Z, Bonacci M, Ariza X, Broquetas T, et al. Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with an interferon-free regimen. Aliment Pharmacol Ther. 2017;45:1156–61. Observational and prospective study evaluating HBV reactivation in patients with co-infection during HCV treatment

    Article  PubMed  Google Scholar 

  42. El-Sherif O, Khoo S, Solas C. Key drug-drug interactions with direct-acting antiviral in HIV-HCV coinfection. Curr Opin HIV AIDS. 2015;10:348–854.

    Article  CAS  PubMed  Google Scholar 

  43. Agarwal K, Fung SK, Nguyen TT, Cheng W, Sicard E, Ryder SD, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol. 2015;62:533–40.

    Article  CAS  PubMed  Google Scholar 

  44. Ayoub WS, Tran TT. Regimens for the hepatitis C treatment-naive patient. Clin Liver Dis. 2015;19:619–27.

    Article  PubMed  Google Scholar 

  45. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology. 2010;139:1593–601.

    Article  CAS  PubMed  Google Scholar 

  46. Manns MP, Pockros PJ, Norkrans G, Smith CI, Morgan TR, Häussinger D, et al. Long-term clearance of hepatitis C virus following interferon α-2b or peginterferon α-2b, alone or in combination with ribavirin. J Viral Hepat. 2013;20:524–9.

    Article  CAS  PubMed  Google Scholar 

  47. Shiffman ML, Sterling RK, Contos M, Hubbard S, Long A, Luketic VA, et al. Long term changes in liver histology following treatment of chronic hepatitis C virus. Ann Hepatol. 2014;13:340–9.

    PubMed  Google Scholar 

  48. Morgan TR, Ghany MG, Kim HY, Snow KK, Shiffman ML, De Santo JL, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52:833–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584–93.

    Article  PubMed  Google Scholar 

  50. Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45:1056–75.

    Article  CAS  PubMed  Google Scholar 

  51. Kohrt HE, Ouyang DL, Keeffe EB. Antiviral prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection. Clin Liver Dis. 2007;11:965–91.

    Article  PubMed  Google Scholar 

  52. Shouval D, Shibolet O. Immunosuppression and HBV reactivation. Semin Liver Dis. 2013;33:167–77.

    Article  CAS  PubMed  Google Scholar 

  53. Asselah T, Marcellin P. Long-term results of treatment with nucleoside and nucleotide analogues (entecavir and tenofovir) for chronic hepatitis B. Clin Liver Dis. 2013;17:445–50.

    Article  PubMed  Google Scholar 

  54. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005;352:2673–81.

    Article  CAS  PubMed  Google Scholar 

  55. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468–75.

    Article  CAS  PubMed  Google Scholar 

  56. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–31.

    Article  CAS  PubMed  Google Scholar 

  57. Konerman MA, Lok AS. Interferon treatment for hepatitis B. Clin Liver Dis. 2016;20:645–65.

    Article  PubMed  Google Scholar 

  58. Sethi A, Shiffman ML. Approach to the management of patients with chronic hepatitis C who failed to achieve sustained virologic response. Clin Liver Dis. 2005;9:453–71.

    Article  PubMed  Google Scholar 

  59. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.

    Article  CAS  PubMed  Google Scholar 

  60. Yu ML, Lee CM, Chen CL, Chuang WL, Lu SN, Liu CH, et al. Sustained hepatitis C virus clearance and increased hepatitis B surface antigen seroclearance in patients with dual chronic hepatitis C and B during posttreatment follow-up. Hepatology. 2013;57:2135–42.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, 5855 Bremo Road, Suite 509, Richmond, VA, 23226, USA

    Mitchell L. Shiffman

  2. Pinnacle Clinical Research, 3001 Bee Caves Road Ste. 220, Rollingwood, TX, 78746, USA

    Nadege T. Gunn

Authors
  1. Mitchell L. Shiffman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nadege T. Gunn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitchell L. Shiffman.

Ethics declarations

Conflict of Interest

Dr. Gunn declares no potential conflict of interest.

Dr. Shiffman reports grants and personal fees from Abbvie, personal fees from Bayer, grants and personal fees from Bristol-Myers-Squibb, grants from Conatus, grants from CymaBay, grants and personal fees from Daiichi Sankyo, grants from Exalenz, grants from Galectin, grants from Genfit, grants and personal fees from Gilead, grants and personal fees from Intercept, grants from Immuron, grants and personal fees from Merck, grants from NGMBio, grants from Novartis, personal fees from Optum Rx, personal fees from Salix, and grants from Shire, outside the submitted work.

Human and Animal Rights and Informed Consent

This article contains no studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Hepatitis B

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shiffman, M.L., Gunn, N.T. Management and Treatment of Chronic HBV and HCV Co-Infection and the Impact of Anti-Viral Therapy. Curr Hepatology Rep 16, 169–177 (2017). https://doi.org/10.1007/s11901-017-0352-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-017-0352-z

Keywords

Search

Navigation