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

Abstract

Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty‐four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta‐analysis of 395 patients showed a pooled SVR rate of 78% (95‐CI 72%–84%) after ribavirin treatment. Twenty‐five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon‐alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon‐alpha increases the risk of transplant rejection and should therefore be administered with great caution.

Hepatitis E case series: A UK experience

“…No median dose was calculated but the range was 29-1200 mg/day. 16 It was also reported that 52% patients required a dose reduction due to anaemia. These studies have a median treatment length of 12 weeks.…”

“…A meta‐analysis published in 2020 reviewed 582 patients who received treatment with ribavirin for chronic hepatitis E. The SVR rate was 76%, and again, the median duration of treatment was 3 months (range 0.3–32). No median dose was calculated but the range was 29–1200 mg/day 16 . It was also reported that 52% patients required a dose reduction due to anaemia.…”

Recapitulating hepatitis E virus–host interactions and facilitating antiviral drug discovery in human liver–derived organoids

“…This bears important biological and therapeutic implications, as inhibiting basal interferon activation by JAK inhibitor further promoted HEV replication, whereas therapeutic treatment with recombinant IFNα inhibited viral replication. PEGylated IFNα has been administered to a small number of chronic HEV patients with about 85% response rate, but this treatment has a high risk of causing acute transplant rejection ( 47 ). HEV replication in cell lines has been shown to barely activate type I but mildly type III interferon response ( 48 ).…”

Transfusion-transmitted hepatitis E: What we know so far?

“…If modification of the immunosuppressant regimen is not possible or is unsuccessful, pharmacological agents such as ribavirin and/or pegylated interferon-alpha (peg-IFN) can be used[ 171 ]. In a meta-analysis that included 395 patients with chronic hepatitis E, ribavirin monotherapy for a median of 3 mo achieved sustained virological response (SVR) in 76% of patients[ 172 ]. The reported dose of ribavirin in the literature ranged from 29 to 1200 mg/d, and the duration from 1 to 18 mo.…”

“…HEV RNA should be assessed in the serum and in the stool before treatment discontinuation[ 169 ]. A second course of ribavirin for 6 mo can be attempted in cases of treatment failure[ 172 ]. HEV RNA concentrations decrease within the first week of initiating ribavirin therapy, and a greater reduction in viral load on day 7 is an independent predictor of SVR[ 174 ].…”