Ribavirin yields lower than expected SVR rates for HEV-infected Asian transplant recipients
Sustained virologic response (SVR) rates with a 12-week course of ribavirin therapy appear to be lower than expected in an Asian cohort of transplant recipients with hepatitis E virus (HEV) infection, with those who received kidney transplant as opposed to other organs being more likely to fail therapy, as reported in a recent study from Singapore.
“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,” according to the investigators.
The analysis involved 10 consecutive HEV RNA-positive patients (mean age, 47 years; 80 percent male) who had received a solid organ transplant (kidney, n=5; liver, n=4; bone marrow, n=1). One of the patients was from United Arab Emirates, and the other nine were Singapore residents.
Nine patients received at least 12 weeks of ribavirin, whereas the remaining patient achieved resolution after reducing immunosuppression therapy. Ribavirin was initiated at a median dose of 600 mg per day, which was equivalent to 9.7 mg per kilogram of body weight per day. The dosages were subsequently adjusted based on the estimated glomerular filtration rate.
At month 3, by the end of therapy, two patients had detectable HEV RNA, with viraemia lasting more than a year despite continuous therapy. Both received reduced ribavirin doses due to side effects and achieved SVR after 1.5 and 3.7 years, respectively. [World J Hepatol 2019;11:553-561]
HEV recurred after initial complete virologic response at the end of therapy in four patients (44 percent), all of whom were kidney transplant recipients. All four of them responded to the second course of ribavirin (12–16 weeks) and achieved durable SVR.
The overall treatment failure rate was 66.7 percent. Being a kidney transplant recipient emerged as the sole significant predictor of failing to achieve an initial SVR (p<0.05).
In terms of safety, anaemia was the most common side effect of ribavirin (mean haemoglobin drop, 3.4 g/dL), with three patients (33.3 percent) transiently interrupting therapy due to severe anaemia. Five patients required blood transfusion, while seven required erythropoietin therapy.
Taken together, the current data indicate that the SVR rate of HEV infection treated with a 12-week ribavirin course is lower than that reported in the Western populations (70 percent), and that kidney transplantation poses a higher risk of relapse possibly because the recipients require higher immunosuppression and have reduced tolerance for higher ribavirin dosages, according to the investigators.
“[A] longer course of ribavirin therapy may be considered in kidney transplant patients who could not tolerate a full dose of ribavirin therapy … [while] a 3-month regimen seems to be sufficient for the remaining organ transplant recipients,” they added.
The investigators stressed that most patients in the study received ribavirin therapy between 1 and 3 months after the first HEV RNA positive result, based on the discretion of the physicians. Hence, HEV infection was not technically chronic by the original definition that requires viral persistence of ≥6 months.
“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 minimize bias,” they said.