New therapies for hepatitis delta virus infection.

Hepatitis delta virus (HDV) infection is a defective virus requiring hepatitis B virus (HBV) for its complete replication cycle. HDV is a small hepatotropic RNA virus and around 15 to 25 million people worldwide are living with chronic hepatitis delta (CHD) infection. However, the prevalence of HDV may be underestimated, and screening is frequently insufficient. HDV infection remains endemic in several regions including Central and West Africa, the Mediterranean basin, the Middle East, Eastern Europe, Northern Asia, certain areas of Southeast Asia and the Amazon basin of South America. The best preventive strategy to decrease HDV infection is to improve coverage of the prophylactic HBV vaccine. HDV infection may occur by HBV-HDV co-infection or superinfection, and the latter is usually more severe. CHD is associated with a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to HBV mono-infection. Pegylated interferon alpha (PEG-IFNα) therapy is limited by moderate effectiveness (around 20%) and its adverse effects. The entry inhibitor, bulevirtide (BLV, Hepcludex® ), which was recently approved in Europe at a dose of 2 mg in sub-cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG-IFNα. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFNλ) (immunomodulator), lonafarnib (prenylation inhibitor) and nucleic acid polymers (Inhibitors of HBsAg release). In this review, we will present an update on CHD and future promising treatments.