Toward antivirals against hepatitis E: In the steps of hepatitis C

Abstract

Infections with the HEV have long been neglected as it was believed that such infections resulted only in self-limiting hepatitis in endemic regions. HEV is a nonenveloped positive-single-stranded RNA virus belonging to the family of the Hepeviridae. HEV-1 and HEV-2 are transmitted through the fecal-oral route and cause epidemics in regions with poor sanitation settings. In pregnant women, up to 25% may develop fulminant hepatitis and acute liver failure with fetal, neonatal, and maternal mortality. [1] The World Health Organization reports that there are annually and globally (but mostly in East and South Asia) an estimated 3.3 million symptomatic cases of hepatitis E, resulting in ~44,000 deaths. A vaccine (Hecolin) has only been approved in China for people aged above 16, who are at high risk of HEV infection. In industrialized countries, HEV-3 and HEV-4 are sources of zoonotically acquired infection through contact or meat consumption from animal species, such as pig, deer, and wild boar. [1] Persistent infection with these genotypes occurs in about 60% of immunosuppressed individuals with a risk for a rapid progression to liver fibrosis, cirrhosis, and end-stage liver disease. Elimination of the virus can be achieved either by relieving the immunosuppression regimen, when possible, or by 3-6 months of off-label treatment with the broadspectrum antiviral drug ribavirin. [1] Hematological toxicity (anemia) is a frequent adverse effect of ribavirin limiting its use. Patients with renal insufficiency or pregnant woman are not eligible for ribavirin therapy. A cure rate of ~65%-80% in patients with chronic hepatitis E has been reported with this drug. Interferon-based regimens may be an alternative, but the increased risk of graft rejection in transplant patients is a strong limitation. There is, thus, an urgent need for one or more potent and safe antiviral drugs for the treatment of (chronic) HEV infection.HEV is, akin to the HCV, a positive single-strand RNA virus. Today, combinations of highly potent and safe antivirals against HCV are successfully used in the treatment and cure of chronic hepatitis C. There is no doubt that it should, given sufficient efforts and investments, also be possible to develop