Ribavirin Therapy in Immunodeficient Patients with Chronic Hepatitis E Virus Infection

Research Article

J Hepat Res. 2021; 6(1): 1044.

Ribavirin Therapy in Immunodeficient Patients with Chronic Hepatitis E Virus Infection

Materacki L¹*, Valliani T¹, Gordon FH²

¹North Bristol Liver Unit, Southmead Hospital, Southmead Road, Bristol, UK

²Department of Liver Medicine, Bristol Royal Infirmary, Upper Maudlin St, Bristol, UK

*Corresponding author: Luke Materacki, North Bristol Liver Unit, Southmead Hospital, Southmead Road, Bristol, UK

Received: May 28, 2021; Accepted: June 25, 2021; Published: July 02, 2021


Hepatitis E virus (HEV) infection, usually self-limiting in immunocompetent individuals, may adopt a chronic course in immunodeficient patients. A low threshold for HEV screening in immunodeficient patients is advocated so early management can be initiated to minimise liver injury.

This retrospective, observational study evaluated all cases (n=11) of chronic HEV diagnosed in immunodeficient patients in 2 university hospitals in Bristol, UK between February 2014 and October 2017. We report our experiences in the management of chronic HEV including ribavirin use.

No patients achieved viral clearance spontaneously or with reduction of immunosuppression and so all were treated with ribavirin. The median time between chronic HEV diagnosis and initiation of ribavirin was 91 days (range, 1–293 days). The median ribavirin dose at initiation was 1000 mg/day (range 800-1200 mg/day) and at cessation was 900 mg/day (range 600–1200 mg/day), reduced due to anaemia.

Different end points guided treatment cessation including negative HEV RNA PCR serology +/- negative stool HEV RNA PCR +/- biochemical remission at various time points. Following ribavirin therapy, HEV relapse occurred in 1 patient. The mean duration of ribavirin therapy, excluding the patient who was re-treated, was 4.6 months. One significant adverse event of severe anaemia requiring transfusion was observed.

This case series supports the use of ribavirin monotherapy for chronic HEV in immunodeficient patients. Anaemia commonly developed prompting ribavirin dose reduction. We advocate 2 consecutive negative serum and stool HEV RNA PCR results sampled at 4 weekly intervals to guide ribavirin cessation.

Keywords: Hepatitis E; Hepatitis; Ribavirin


HEV: Hepatitis E Virus; SOT: Solid Organ Transplant; EASL: European Association for the Study of the Liver; HIV: Human Immunodeficiency Virus; RNA: Ribonucleic Acid; SVR: Spontaneous Virological Response; NHS: National Health Service; CKD: Chronic Kidney Disease; RR: Reference Range; ALT: Alanine Aminotransferase; PCR: Polymerase Chain Reaction; ARFI: Acoustic Radiation Force Impulse


HEV is the most common cause of acute viral hepatitis in the UK. Although infection is usually self-limiting, immunosuppressed patients may fail to eradicate the virus leading to chronic infection [1]. This may induce accelerated liver fibrosis, leading to cirrhosis in some patients [2]. Prompt diagnosis and treatment of chronic HEV is important as liver fibrosis may regress after viral clearance.

A large multi-centre retrospective study of SOT recipients with chronic HEV found cirrhosis developed in 10% [3]. No patients were identified in this study who spontaneously cleared the virus between 3 and 6 months after infection. Subsequent EASL clinical practice guidelines have recommended that chronic infection be defined as patients with persistent viraemia for more than 3 months, for the purposes of treatment [4].

HEV infection may manifest with subtle or no symptoms making diagnosis challenging. The clinical presentation of chronic HEV infection is similar in patients with haematological disorders, HIV, rheumatological conditions receiving heavy immunosuppression and SOT recipients [4]. Most patients will be asymptomatic but coryzal symptoms, tiredness, malaise and fever may be reported and physicians should exercise a low threshold for testing liver biochemistry, including a viral liver screen, if any symptoms are identified, particularly in immunocompromised patients. Similar practice should be adopted if liver dysfunction is detected during monitoring in asymptomatic patients taking immunosuppression.

Following HEV exposure, 50% to 67% of SOT recipients will develop chronic HEV hepatitis. This risk is increased by a low platelet count at the time of diagnosis of infection and the use of tacrolimusbased immunosuppressive therapy (rather than cyclosporine A) [2]. Reducing immunosuppressive therapy achieves sustained viral clearance in 30% of SOT recipients [4]. Those SOT recipients who spontaneously achieved viral clearance had a lower tacrolimus level and a lower daily steroid dose compared to those who remained viraemic [4]. If HEV clearance is not spontaneously achieved by reducing immunosuppressive therapy, EASL recommend a 3 month course of ribavirin monotherapy, extended to 6 months if HEV RNA remains detectable or if there is relapse after ceasing ribavirin [4]. Second-line therapy with pegylated interferon for 3 months can be considered in liver transplant patients who fail ribavirin.

Predicting which patients with chronic HEV who are less likely to achieve SVR with conventional therapy is desirable so a more tailored treatment regimen can be instigated early. The optimal ribavirin dose and duration of therapy to treat chronic HEV remains unanswered. We report a combined case series from 2 hospitals in Bristol, United Kingdom of immunocompromised patients with chronic HEV who were treated with ribavirin.

Materials and Methods

This retrospective, observational study evaluated all cases of chronic HEV diagnosed with ribavirin monotherapy in North Bristol NHS Trust and University Hospitals Bristol and Weston NHS Trust between February 2014 and October 2017 (11 patients). Chronic HEV infection was defined by the presence of persistent HEV RNA detectable in the serum for at least 3 months before treatment was commenced using analysis of frozen serum if necessary. All samples were analysed by quantitative PCR at the UK reference centre for HEV in Colindale, London. Clinical data was collected from patients’ written and electronic medical records. SVR was defined as an undetectable level of HEV RNA in the serum and stool at least 6 months post-ribavirin therapy.


Patient characteristics (Table 1)

Citation: Materacki L, Valliani T, Gordon FH. Ribavirin Therapy in Immunodeficient Patients with Chronic Hepatitis E Virus Infection. J Hepat Res. 2021; 6(1): 1044.