1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
2Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany; German Center for Infection Research (DZIF), Partner Side Hannover/Braunschweig. Electronic address: Wedemeyer.Heiner@mh-hannover.de.
Chronic hepatitis D virus (HDV) infection is the most severe form of viral hepatitis with high rates of end-stage liver disease and hepatocellular carcinoma. Therefore, effective antiviral treatment strategies are needed desperately. Until recently, antiviral treatment was limited to pegylated interferon-alpha. With the conditional approval of the entry inhibitor bulevirtide by the European Medicines Agency, new treatment options are now available. In addition, multiple other antiviral compounds are currently tested in clinical phase II and III trials and represent promising agents for the treatment of chronic HDV infection.
Jacobson, I. (2021) Sandmann L , Wedemeyer, H. New Treatments for Chronic Hepatitis B Virus/Hepatitis D Virus Infection. Clin Liver Dis. 2021 Nov;25(4):831-839.
This is a very readable, concise summary of the basic aspects of HDV biology, including epidemiology, viral structure and life cycle, interferon therapy, and novel agents. It includes a clear diagram of the replication cycle and other sites amenable to therapeutic targeting. The authors underscore the pathogenicity of hepatitis D virus (HDV), the maxim that every HBV-positive patient should have at least a one-time test for HDV, and the diagnostic testing pathway consisting of HDV antibody followed by PCR for HDV RNA. Therapy is heavily featured and includes the data on peginterferon and the recently approved entry inhibitor bulevirtide. This drug binds to the sodium taurocholate peptide (NTCP), famously discovered to be the receptor for HBV entry nearly a decade ago, thereby blocking the entry of HBV or HDV into hepatocytes. Other novel agents covered include the prenylation inhibitor lonafarnib, which blocks a critical step in the synthesis of the large hepatitis D antigen, nucleic acid polymers, and interferon lambda. The senior author is one of the world’s leading investigators in the HDV field.