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

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.

Epidemiology and treatment of hepatitis E in the liver transplantation setting: A literature review

“…In addition, 27 studies 5,14,15,18,22,26–47 were evaluated for the second arm on HEV treatment, including 118 LT recipients (6 of them with dual liver/kidney and 1 with liver/heart recipients) treated with various regimens for HEV infection (Table 3).…”

“…Twenty seven studies 5,14,15,18,22,26–47 (16 case reports, 2 case series, 9 cohorts) reported the outcomes of 118 LT recipients with confirmed HEV infection Table 3. Median age of patients was 55 (32–64) years old and mean time from transplantation was 19 (2–216) months.…”

“…SVR was also achieved in a patient treated with immunosuppression reduction and valganciclovir, another patient treated with RBV and SOF and one patient who remained untreated, while SVR was not achieved in two patients treated with Peg‐IFNa (one with immunosuppression reduction and one with RBV) and a patient treated with SOF, but no statistical analysis could be performed due to the small number of patients. In patients with RBV as 1st line regimen, cases with and without SVR had similar duration [12 (4–40) vs. 12 (12–24) months, p = .77] and dose of RBV [600 (400–1200) vs. 600 (600–800) mg, p = 1.00] (Figure S1).…”

Treatment for chronic hepatitis E virus infection: A systematic review and meta‐analysis

“…Treatment effect of RBV was described in 34 studies 22,23,25‐27,32,34‐36,38‐62 . The majority of the 395 patients treated with RBV was male, and almost all patients were SOT recipients.…”

Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients

“…In this sense, clinical guidelines recommend a program therapy duration of 12 weeks using RBV at the initiation with a weight-adjusted dose or a dose adjusted on the basis of the estimated glomerular filtration rate [12,13,23]. Following these recommendations, a total of 176 transplant patients have been reported, and 129 of these patients have achieved SVR (73.2%) [11,[24][25][26][27][28][29][30][31][32][33]. Therefore, this recommendation seems to be highly effective for the treatment of HEV infection in transplant recipients infected by genotype 3 HEV.…”