Therapy of Delta Hepatitis

Abstract

Delta hepatitis is the less frequently encountered but most severe form of viral hepatitis. Acute delta hepatitis, as a result of coinfection with hepatitis B and hepatitis delta, is rare, but may lead to fulminant hepatitis, and no therapy exists for this form. Chronic delta hepatitis (CDH) mostly develops as a result of superinfection of a hepatitis B surface antigen (HBsAg) carrier with hepatitis delta virus (HDV). In general, HDV is the dominant virus. However, a dynamic shift of the dominant virus may occur with time in rare instances, and hepatitis B virus (HBV) may become the dominant virus, at which time nucleos(t)ide analog therapy may be indicated. Otherwise, the only established management of CDH consists of conventional or pegylated interferon therapy, which has to be administered at doses used for hepatitis B for a duration of at least 1 year. Posttreatment week-24 virologic response is the most widely used surrogate marker of treatment efficacy, but it does not represent a sustained virologic response, and late relapse can occur. As an easy-to-use simple serological test, anti-HDV-immunoglobulin M (IgM) correlates with histological inflammatory activity and clinical long-term outcome; however, it is not as sensitive as HDV RNA in assessing treatment response. No evidence-based rules for treating CDH exist, and treatment duration needs to be individualized based on virologic response at end of treatment or end of follow-up. Effective treatment may decrease liver-related complications, such as decompensation or liver-related mortality. In patients with decompensated cirrhosis, interferons are contraindicated and liver transplantation has to be considered. Alternative treatment options are an urgent need in CDH. New treatment strategies targeting different steps of the HDV life cycle, such as hepatocyte entry inhibitors or prenylation inhibitors, are emerging and provide hope for the future.