Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection

World J Hepatol. 2019 Jun 27;11(6):553-561. doi: 10.4254/wjh.v11.i6.553.

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: Antiviral agents; Hepatitis E virus; Immune responses; Persistent infection; Systemic immunity; Toxicity; Virus classification.