Published online Jun 27, 2019. doi: 10.4254/wjh.v11.i6.553
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
There has been an increase in the amount of literature and our understanding of Hepatitis E virus (HEV) infection since the landmark paper by Kamar et al in 2014. This study describes the outcome of HEV treatment in a transplant center in Singapore, where immunosuppressed Asian hosts appear to have lower sustained virologic response (SVR) rates after a 12-wk course of ribavirin than reported earlier.
Singapore is a unique industrialized country where, although ethnic Chinese make up 76% of the population, it is a thriving hub with many international visitors. Seven genotypes of HEV have been described so far, and studies have reported a rate of chronicity of 50%-60%. Ribavirin is considered an effective treatment option for chronic HEV in post-transplant patients, where success rates > 75% have been reported in France and Germany alongside a reduction in immunosuppression dose. Since most clinical studies come from Europe and the United States, there is a pressing need to characterize and investigate the state of chronic HEV infection in Asian populations.
Our report describes the first 10 consecutive cases of hepatitis E diagnosed in post-transplant patients in an organ transplant center in Singapore.
This is a retrospective case series that studied all newly diagnosed HEV infections in post-transplant patients from May 2012 to September 2015. Subjects who had transaminitis that were caused by persistent HEV replication were treated with ribavirin, and the results were collected and tabulated. Data from the first 10 HEV RNA-positive patients who had received a solid organ transplant (5 kidney transplant recipients, 4 liver-transplant recipients, and 1 bone marrow transplant recipient) were analysed.
One of the patients was from United Arab Emirates, and the other nine were Singapore residents. The median starting dose of ribavirin was 600 mg per day. The dosages were subsequently adjusted based on the estimated GFR. In more than half of patients (5 out of 9), dose reductions of ribavirin were necessary due to clinically significant anemia. The overall failure rate of achieving sustained viral clearance for a 12-wk course of ribavirin was 66.67% (delayed virologic response plus viral recurrence after completing treatment) – far higher than that reported in Western populations. All four patients with viremia recurrence were kidney transplant recipients, which was found to be the only statistically significant predictive factor. The most common side effect of ribavirin was anemia.
This study proposes that kidney transplant recipients, particularly those with poorer renal function, are more susceptible to the adverse effects of ribavirin. Asian patients with lower body weight may be even more likely to suffer from the side effects. This Asian single-centre case series shows that the SVR rate of HEV infection treated with a 12-wk course of ribavirin may be lower than reported earlier. Kidney transplant recipients are at higher risk of relapse, possibly due to higher immunosuppression requirements and reduced tolerance for higher ribavirin dosages.
More effective therapy for chronic HEV infection may be needed, including more accurate markers to predict ribavirin response. A large, prospective, controlled study comparing kidney transplants and other groups of chronic HEV patients will be useful to confirm the results of this study and minimise bias.