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

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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.


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.


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.


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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Fig. 1
Fig. 2
Fig. 3
Fig. 4



Alkaline phosphatase


Alanine aminotransferase


Antibody to Hepatitis B core antigen


Antibody to Hepatitis B e antigen


Anti-Hepatitis B surface antigen


Aspartate aminotransferase




Hepatitis B immunoglobulin


Hepatitis B e antigen


Hepatitis B surface antigen


Hepatitis B virus


Hepatocellular carcinoma


High potency (nucleoside analog)


International normalized ratio






Liver transplantation


Low potency (nucleoside analog)


Model for end-stage liver disease


Nucleos(t)ide analog


Orthotopic liver transplantation




Upper limit of normal


Viral load


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Author information

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.

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.

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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 (2020) doi:10.1007/s12072-019-10011-2

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  • HBIG
  • Hepatitis B
  • Liver transplant
  • Nucleoside analogs
  • Low potency
  • High potency
  • Lamivudine
  • Tenofovir
  • Entecavir
  • Asian