Antiviral Therapy in Chronic Hepatitis E

A Systematic Review

A. M. Peters van Ton; T. J. G. Gevers; J. P. H. Drenth


J Viral Hepat. 2015;22(12):965-973. 

In This Article

Abstract and Introduction


Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon-α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and for articles and abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty-four studies matched our criteria, representing a total of 105 ribavirin-treated and 8 pegylated interferon-treated patients. The majority of patients had a solid organ transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon-treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.


Chronic hepatitis E infections are seen in an increasing rate.[1–3] In contrast to acute hepatitis E, which causes a self-limiting and sometimes asymptomatic infection in immunocompetent patients, chronic hepatitis E can develop into progressive liver disease that rapidly evolves to cirrhosis.[2] The culprit, hepatitis E virus (HEV), is a nonenveloped single-stranded RNA virus. Molecular characterization of various HEV strains has identified that HEV genotype 3 is the most common cause of chronic hepatitis E.[2] HEV is transmitted via uncooked pig, swine or other meat and is responsible for sporadic cases of autochthonous cases of hepatitis E in both developing and developed countries with a worldwide distribution.[1,3] Patients with haematological disorders, HIV infection and solid organ transplant patients under immunosuppressives are particularly at risk for chronic HEV infection.[2,4] HEV infection can be lethal in these specific subgroups and therefore requires treatment.

The optimal therapy for chronic hepatitis E is currently under debate. Studies show that reduction of immunosuppressive medication leads to spontaneous viral clearance in a third of patients.[5,6] However, many of these patients depend on their immunosuppressants to control their comorbidity. Case reports have shown that antiviral drugs such as ribavirin and pegylated interferon-α (peginterferon) lead to viral clearance in patients with severe hepatitis E.[7–12] Peginterferon is a strong immunostimulatory drug that is being used for the treatment of chronic hepatitis B and C infections.[11] However, it is suggested to induce allogenic immunity, leading to transplant rejection in patients after solid organ transplantation,[13] which possibly limits its use in the treatment of chronic hepatitis E. Ribavirin is an antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. Although anecdotal reports suggest the beneficial effect from both antivirals for chronic hepatitis E, these therapies are still experimental. The optimal dose, duration of therapy, timing of initiating treatment and its safety are unknown. No guidelines have been formulated yet, and both peginterferon and ribavirin have not been approved for this indication. This systematic review aims to evaluate efficacy and safety of ribavirin and pegylated interferon treatment in chronic hepatitis E.