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Nucleoside analog monotherapy for prophylaxis in Hepatitis B liver transplant patients is safe and efficacious

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Abstract

Background

Combination therapy with HBIG and NAs has reduced HBV recurrence post LT. Despite its efficacy, costs of HBIG remain prohibitive. With high-potency NAs, HBIG’s use has been questioned. We aim to evaluate the efficacy and safety of HBIG-free regimens in patients transplanted for HBV-related liver disease.

Methods

A review of LT patients at the National University Hospital, Singapore from 2001 to 2015 was performed. Patients transplanted for HBV were divided by antiviral treatment received: high- or low-potency NAs, or a combination of HBIG with high-potency NAs. Post-transplant outcomes were reviewed till data censure. Primary outcome was recurrence of HBV viremia post-transplant, while secondary outcomes were HBsAg sero-clearance, graft survival and mortality.

Results

Among 58 patients, 51 (88%) had persistent HBV viral suppression. Patients on a high-potency agent had significantly higher viral suppression compared to those on a low-potency agent (97% vs 72%, p = 0.02). This was also seen in patients with VL detectable at transplant (100% vs 50%, p < 0.01). None of the 16 patients with VL detectable at transplant and treated with high-potency agents developed recurrence. 42 patients (72%) achieved persistent HBsAg sero-clearance. Although this was higher in the high-potency NA-only group, it was not statistically significant (p = 0.56). There were no graft failures or mortalities attributed to HBV recurrence.

Conclusion

With the use of high-potency agents, HBIG may not be necessary in the treatment of patients transplanted for HBV-related liver disease, even in the presence of detectable VL at time of transplant.

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Abbreviations

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

Anti-HBc:

Antibody to Hepatitis B core antigen

Anti-HBe:

Antibody to Hepatitis B e antigen

Anti-HBs:

Anti-Hepatitis B surface antigen

AST:

Aspartate aminotransferase

ETV:

Entecavir

HBIG:

Hepatitis B immunoglobulin

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HP:

High potency (nucleoside analog)

INR:

International normalized ratio

LAM:

Lamivudine

LdT:

Telbivudine

LT:

Liver transplantation

LP:

Low potency (nucleoside analog)

MELD:

Model for end-stage liver disease

NA:

Nucleos(t)ide analog

OLTx:

Orthotopic liver transplantation

TDF:

Tenofovir

ULN:

Upper limit of normal

VL:

Viral load

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Author information

Author notes

  1. Mark D. Muthiah and En Ying Tan contributed equally as first authors.

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, National University Health System, 5 Lower Kent Ridge Road, Main Building Level 1, Singapore, 119074, Singapore

    Mark D. Muthiah, Daniel Q. Y. Huang, Seng Gee Lim, Yock Young Dan, Poh Seng Tan, Guan Huei Lee & Boon Leng Lim

  2. National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore

    Mark D. Muthiah, Daniel Q. Y. Huang, Glenn K. Bonney, Alfred W. C. Kow, Seng Gee Lim, Yock Young Dan, Poh Seng Tan, Guan Huei Lee & Boon Leng Lim

  3. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Mark D. Muthiah, Daniel Q. Y. Huang, Seng Gee Lim, Yock Young Dan, Poh Seng Tan & Guan Huei Lee

  4. University Medicine Cluster, National University Health System, Singapore, Singapore

    En Ying Tan & Sin Hui Melissa Chua

  5. Department of Hepatobiliary and Pancreatic Surgery, National University Health System, Singapore, Singapore

    Glenn K. Bonney & Alfred W. C. Kow

Authors
  1. Mark D. Muthiah
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Contributions

MDM, study concept and design, data acquisition and analysis, statistical analysis, drafting of manuscript, review of content. EYT, data acquisition and analysis, statistical analysis, drafting of manuscript, review of content. SHMC, data acquisition and analysis, statistical analysis, review of content. GB, AWCK, SGL, YYD, PST review of content, study supervision. GHL, BLL study concept and design, data analysis, review of content, study supervision.

Corresponding author

Correspondence to Guan Huei Lee.

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Conflict of interest

Mark Muthiah, En Ying Tan, Sin Hui Melissa Chua, Daniel Huang, Glenn Bonney, Alfred Kow, Seng Gee Lim, Yock Young Dan, Poh Seng Tan, Guan Huei Lee and Boon Leng Lim declare that they have no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

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Informed consent was obtained from all patients for being included in the study.

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Muthiah, M.D., Tan, E.Y., Chua, S.H.M. et al. Nucleoside analog monotherapy for prophylaxis in Hepatitis B liver transplant patients is safe and efficacious. Hepatol Int 14, 57–69 (2020). https://doi.org/10.1007/s12072-019-10011-2

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  • DOI: https://doi.org/10.1007/s12072-019-10011-2

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