Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2019; 11(6): 553-561
Published online Jun 27, 2019. doi: 10.4254/wjh.v11.i6.553
Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection
En Xian Sarah Low, Edhel Tripon, Kieron Lim, Poh Seng Tan, How Cheng Low, Yock Young Dan, Yin Mei Lee, Mark Muthiah, Wai Mun Loo, Calvin Jianyi Koh, Wah Wah Phyo, JunXiong Pang, Seng Gee Lim, Guan-Huei Lee
En Xian Sarah Low, Department of Medicine, Ng Teng Fong General Hospital, National University Health System, Singapore 609606, Singapore
Edhel Tripon, Centre for Liver Disease Management and Transplant of Medical City, Manila 1605, Philippines
Kieron Lim, Mount Elizabeth Medical Centre, Singapore 228510, Singapore
Poh Seng Tan, How Cheng Low, Yock Young Dan, Yin Mei Lee, Mark Muthiah, Wai Mun Loo, Calvin Jianyi Koh, Seng Gee Lim, Guan-Huei Lee, Division of Gastroenterology and Hepatology, National University Health System, Singapore 119228, Singapore
Wah Wah Phyo, Department of Medicine, National University of Singapore, Singapore 119077, Singapore
JunXiong Pang, Centre for Infectious Disease Epidemiology and Research, National University of Singapore, Singapore 117549, Singapore
Seng Gee Lim, Guan-Huei Lee, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Author contributions: Low EXS compiled the data and wrote the main section of the manuscript; Tripon E collected the patient data and carried out the initial analysis; Lim K, Tan PS, Low HC, Dan YY, Koh CJ and Lee YM were involved in subject recruitment and data collection; Muthiah M, Loo WM, and Phyo WW carried out the statistical analysis and preparation of the tables and figures; Lim SG assisted in the study design and edited the manuscript; Pang JX assisted in the biostatistics statement and edited the manuscript; Lee GH designed the study and wrote the final version of the manuscript.
Institutional review board statement: The study is approved by the NHG Domain Specific Review Board.
Informed consent statement: All involved subjects provided consent for study participation.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Guan-Huei Lee, MBBS, MRCP, PhD, Attending Doctor, Division of Gastroenterology and Hepatology, National University Health System, 1E Kent Ridge Road, Singapore 119228, Singapore. guan_huei_lee@nuhs.edu.sg
Telephone: +65-67795555
Received: February 12, 2019
Peer-review started: February 13, 2019
First decision: April 11, 2019
Revised: June 11, 2019
Accepted: June 17, 2019
Article in press: June 17, 2019
Published online: June 27, 2019
Abstract
BACKGROUND

Hepatitis E virus (HEV) infection is a cause of chronic hepatitis in immunosuppressed patients. Sustained virologic response rates to a 12-wk course of ribavirin therapy were reported to be > 70% in the West. This study describes the outcome of HEV treatment in a transplant center in Singapore.

AIM

To study the outcome of ribavirin treatment in a series of chronic HEV patients, and the cause of treatment failure.

METHODS

We studied all of the transplant recipients who were diagnosed with HEV infection between 2012 to 2015. The outcome of therapy and virologic relapse are monitored for three years after the end of therapy.

RESULTS

Ten transplant recipients (4 liver, 5 kidney, and 1 bone marrow transplantation) with positive HEV RNA were studied. Nine patients received at least 12 wk of ribavirin therapy, and the remaining patient resolved after reducing immunosuppression therapy. Two subjects had prolonged viremia that lasted more than one year, despite continuous ribavirin therapy. Four ribavirin-treated patients (44.4%) had HEV RNA relapse after achieving a virologic response by the end of treatment. The overall failure rate is 66.7%. Being a kidney transplant recipient is the strongest risk factor for not achieving an initial sustained virologic response (0/5 treated, Chi-Square test, P < 0.05). The most common side effect of ribavirin is anemia (100%) (haemoglobin reduction of 3-6.2 g/dL). Seven patients required either a blood transfusion or erythropoietin therapy.

CONCLUSION

The sustained virologic response rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than expected. Kidney transplant recipients had a higher rate of treatment failure due to higher immunosuppression requirements and adverse effects.

Keywords: Toxicity, Antiviral agents, Hepatitis E virus, Virus classification, Systemic immunity, Immune responses, Persistent infection

Core tip: Hepatitis E virus (HEV) infection is a cause of chronic hepatitis in immunosuppressed patients. Sustained virologic response (SVR) rate to a 12-wk course of ribavirin therapy was reported to be > 70% in the West. This study describes the outcome of HEV treatment in a transplant centre in Singapore. Ten transplant recipients (liver, kidney, bone marrow transplantation) with positive HEV RNA were studied. The SVR rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than expected; an overall failure rate of 66.7%. Kidney transplant recipients had a higher treatment failure due to higher immunosuppression requirements and adverse effects.