Advertisement

Current Treatment Options in Infectious Diseases

, Volume 9, Issue 4, pp 380–388 | Cite as

Reactivation of Occult HBV Infection in Patients Cured of HCV With Direct-Acting Antivirals

  • Karen Ma
  • Susanne Shokoohi
  • Nancy Reau
Hepatitis C (J Raybould, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Hepatitis C

Opinion statement

The era of hepatitis C virus (HCV) treatment with direct-acting antiviral (DAA) therapy has remarkably improved liver-related morbidity and overall mortality with patients achieving rapid and sustained clearance of HCV infection. The initial DAA clinical trials excluded patients with hepatitis B virus (HBV) co-infection, and thus potential complications were unforeseen until case reports of HBV reactivation associated with DAA therapy began to emerge. A recent United States Food and Drug Administration (FDA) drug safety communication has brought public attention to the issue of HBV reactivation in patients treated with DAA for HCV co-infection. Reactivation of HBV is well known to occur with a variety of immune-suppressive therapies notably in the context of cancer, rheumatologic treatments, and organ transplantation. While HBV reactivation in the setting of DAA therapy remains rare, the severity of hepatitis can be profound and deadly. Early recognition and treatment are keys to improving patient outcomes. Therefore, it is currently recommended to screen all patients for current or prior HBV infection prior to starting DAA therapy. If either hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc) is positive, HBV DNA should be obtained. With active viremia, prophylactic therapy should be started with DAA treatment with an agent with a high barrier for resistance. If there is no evidence of active viremia, the risks and benefits of prophylactic therapy should be weighed. Those with positive HBsAg should consider prophylactic therapy. Those with an isolated anti-HBc in the absence of HBsAg have an option of monitoring their liver enzymes, HBV DNA, and HBsAg at regular intervals during DAA therapy. If prophylactic HBV therapy is initiated, it should be continued for at least 3 months after DAA therapy is complete. After this period, the risks and benefits of continuing their HBV therapy should be re-addressed.

Keywords

Hepatitis B reactivation HCV direct-acting antivirals Acute hepatitis HBV/HCV co-infection 

Notes

Compliance with ethical standards

Conflict of interest

Karen Ma has no relevant disclosures to report.

Susanne Shokoohi has no relevant disclosures to report.

Nancy Reau: Consultation: AbbVie, Abbott, Gilead, Merck; Research funding: AbbVie.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

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

  1. 1.
    Sagnelli C, Macera M, Pisaturo M, et al. Occult HBV infection in the oncohematological setting. Infection. 2016;44:575–82.CrossRefPubMedGoogle Scholar
  2. 2.
    Tyson GL, Kramer JR, Duan Z, et al. Prevalence and predictors of hepatitis B virus coinfection in a United States cohort of hepatitis C virus-infected patients. Hepatology. 2013;58:538–45.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87.CrossRefPubMedGoogle Scholar
  4. 4.
    • Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naïve patients: the COSMOS randomized study. Lancet. 2014;384:1756–65. Demonstrated that the combination of simeprevir and sofosbuvir led to a high rate of SVR12 in a patient population traditionally felt difficult to cureCrossRefPubMedGoogle Scholar
  5. 5.
    FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis. https://www.fda.gov/Drugs/DrugSafety/ucm522932.htm. Accessed 10 May 2017.
  6. 6.
    Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148:519–52.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    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;36:2084–6.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Liaw YF, Chen YC, Sheen IS, et al. Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. Gastroenterology. 2004;126:1024–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Biliotti E, Kondili LA, Furlan C, et al. Acute hepatitis B in patients with or without underlying chronic HCV infection. J Inf Secur. 2008;57:152–7.Google Scholar
  10. 10.
    Balagopal A, Thio CL. Another call to cure hepatitis B. Clin Infect Dis. 2015;61:1307–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Liu JY, Sheng YJ, Hu HD, et al. The influence of hepatitis B virus on antiviral treatment with interferon and ribavirin in Asian patients with hepatitis C virus/hepatitis B virus coinfection: a meta-analysis. Virol J. 2012;9:186.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Yalcin K, Degertekin H, Yildiz F, Kilinc N. A severe hepatitis flare in an HBV-HCV coinfected patient during combination therapy with A-interferon and ribavirin. J Gastroenterol. 2003;38:796–800.CrossRefPubMedGoogle Scholar
  13. 13.
    Fabbri G, Mastrorosa I, Vergori A, et al. Reactivation of occult HBV infection in an HIV/HCV co-infected patient successfully treated with sofosbuvir/ledipasvir: a case report and review of the literature. BMC Infect Dis. 2017;17:182.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Collins JM, Raphael KL, Terry C, et al. Hepatitis B virus reactivation during successful treatment of hepatitis C virus with sofosbuvir and simepravir. Clin Infect Dis. 2015;61:1304–6.CrossRefPubMedGoogle Scholar
  15. 15.
    • 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;66:27–36. A large cohort study of veterans infected with chronic hepatitis B infection who were treated with DAA therapy which reports on the prevalence and characteristics of HBV reactivationCrossRefPubMedGoogle Scholar
  16. 16.
    Chen G, Wang C, Chen J, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: a systematic review and meta-analysis. Hepatology. 2017;66:13–26.CrossRefPubMedGoogle Scholar
  17. 17.
    De Monte A, Courjon J, Anty R, et al. Direct-acting antiviral treatment in adults infected with hepatitis C virus: reaction of hepatitis B virus coinfection as a further challenge. J Clin Virol. 2016;78:27–30.CrossRefPubMedGoogle Scholar
  18. 18.
    Lepelletier C, Salmona M, Bercot B, et al. First description of past hepatitis B virus infection acute reactivation occurring in a human immunodeficiency virus infected patient as manifestation of immune reconstitution inflammatory syndrome. J Infect Chemother. 2016;22:490–4.CrossRefPubMedGoogle Scholar
  19. 19.••
    AASLD-IDSA: Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. 10 May 2017. Combined hepatology and infectious diseases societal guidelines on the evaluation and management of hepatitis C infection.
  20. 20.
    European Association for the Study of the Liver. EASL clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.CrossRefGoogle Scholar
  21. 21.
    Launay O, Masurel J, Servant-Delmas A, et al. High levels of serum hepatitis B virus DNA in patients with ‘anti-HBc alone’: role of HBsAg mutants. J Viral Hepat. 2011;18:721–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Terrault NA, Bzowej NH, Chang K-M, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–83.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Division of Digestive Diseases, Department of Internal MedicineRush University Medical CenterChicagoUSA
  2. 2.Section of Hepatology, Division of Digestive Diseases, Department of Internal MedicineRush University Medical CenterChicagoUSA

Personalised recommendations