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Low Rate of Hepatitis B Reactivation Among Patients with Chronic Hepatitis C During Direct Acting Antiviral Therapy

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Abstract

Background and Aims

Hepatitis B virus (HBV) reactivation has been reported in patients co-infected with hepatitis C virus (HCV) during direct acting antiviral (DAA) therapy, leading the United States Food and Drug Administration (U.S. FDA) to issue a black box warning on all DAA drug labels recommending monitoring for HBV reactivation. We conducted a comprehensive evaluation to assess the rate of HBV reactivation among patients with chronic hepatitis C (CHC) during DAA therapy.

Methods

Patients with CHC and recovered HBV infection (hepatitis B surface antigen negative (HBsAg)/anti-hepatitis B core positive), treated with DAAs were included if stored sera were available. Samples were tested for HBV DNA, HBsAg, and ALT. HBV reactivation was considered if (1) HBV DNA was undetectable pre-DAA therapy and became detectable post-therapy, or (2) HBV DNA was detectable pre-treatment, but not quantifiable (< 20 IU/mL) and became quantifiable post-treatment.

Result

79 patients with median age of 62 years were included. 68% were male and Caucasian. Various DAA regimens were administered for 12–24 weeks. Reactivation occurred in 8/79 (10%) of patients and occurred more frequently in men compared to women: 6 during treatment and 2 after treatment. Neither an ALT flare nor HBsAg seroreversion were observed. Detectable HBV DNA was transient in 5/8 and could not be determined in 3/8 but ALT flares were not observed in follow-up of these patients.

Conclusion

The risk of HBV reactivation was low in CHC patients with resolved HBV during DAA therapy. Our data support testing for HBV DNA only in selected patients with ALT flares or failure of ALT normalization during DAA treatment.

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Abbreviations

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

DAA:

Direct acting antiviral

U.S. FDA:

United States Food and Drug Administration

CHC:

Chronic hepatitis C

CD20:

Cluster of differentiate 20

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

ALKP:

Alkaline phosphatase

DNA:

Deoxyribonucleic acid

RNA:

Ribonucleic acid

ULN:

Upper limit of normal

pegIFN:

Pegylated interferon

HBsAg:

Hepatitis B surface antigen

Anti-HBc:

Hepatitis B core antibody

ETV:

Entecavir

LDB:

Liver diseases branch

NIDDK:

National Institute of Diabetes and Digestive and Kidney Diseases

NIH:

National Institutes of Health

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Funding

The study was supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases.

Author information

Authors and Affiliations

  1. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Nehna Abdul Majeed, Ahmad Samer Alawad & Marc G. Ghany

  2. Toronto Centre for Liver Disease, Toronto General Hospital, Toronto, Canada

    Kin Seng Liem, Jordan J. Feld & Harry L. A. Janssen

  3. Institute of Medical Science, University of Toronto, Toronto, Canada

    Kin Seng Liem, Jordan J. Feld & Harry L. A. Janssen

  4. The Toronto Viral Hepatitis Care Network (VIRCAN), Toronto, Canada

    Kin Seng Liem, Jordan J. Feld & Harry L. A. Janssen

  5. Department of Gastroenterology, Alta Bates Summit Medical Center, Oakland, CA, USA

    Varun Takyar

  6. Transfusion Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Harvey Alter

  7. Liver Disease & Transplantation, Erasmus MC, Rotterdam, Netherlands

    Harry L. A. Janssen

  8. Liver Diseases Branch, NIDDK, NIH, Bldg 10, Room 9B-16, 10 Center Drive, MSC 1800, Bethesda, MD, 20892-1800, USA

    Marc G. Ghany

Authors
  1. Nehna Abdul Majeed
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  2. Ahmad Samer Alawad
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  3. Kin Seng Liem
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  4. Varun Takyar
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  5. Harvey Alter
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  6. Jordan J. Feld
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  7. Harry L. A. Janssen
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  8. Marc G. Ghany
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Contributions

NAM: analysis and interpretation and data, statistical analysis, drafting of the manuscript, critical revision for intellectual content. ASA, KSL, JJF: study concept and design, acquisition of data, analysis and interpretation and data, statistical analysis, critical revision for intellectual content. VK: study concept and design, acquisition of data, analysis and interpretation and data, critical revision for intellectual content. HA, HLAJ: study concept and design, acquisition of data, statistical analysis, critical revision for intellectual content. MGG: study concept and design, acquisition of data, analysis and interpretation and data, statistical analysis, drafting of the manuscript, critical revision for intellectual content.

Corresponding author

Correspondence to Marc G. Ghany.

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The authors declare that they have no conflict of interest.

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Marc G. Ghany accepts full responsibility for the conduct of the study.

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Cite this article

Majeed, N.A., Alawad, A.S., Liem, K.S. et al. Low Rate of Hepatitis B Reactivation Among Patients with Chronic Hepatitis C During Direct Acting Antiviral Therapy. Dig Dis Sci 68, 3193–3198 (2023). https://doi.org/10.1007/s10620-023-07916-2

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  • DOI: https://doi.org/10.1007/s10620-023-07916-2

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