New Medications Offer Promise in Treating HDV/HBV Coinfection

While the focus of the World Health Organization has been aimed eliminating hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, the authors of a review of hepatitis D note that “little attention has been reserved to… [this] satellite virus coinfecting with HBV.”

They point out, “Once chronic HDV infection is established, it usually exacerbates the pre-existing chronic hepatitis B,” which is estimated to infect between 240 to 350 million people worldwide. “This constitutes a major contributor to viral hepatitis-associated cirrhosis, hepatocellular carcinoma (HCC), and mortality,” they state.

Although most coinfection cases occur among adults with competent immunity systems, who are able to clear the virus, about 20% of these cases progress to chronic infection with both HBV and HDV. “Chronic hepatitis D is considered to be associated with the most severe form of chronic viral hepatitis, with a rapid progression towards fibrosis/cirrhosis and subsequent liver decompensation. Longitudinal studies have confirmed that a large proportion of chronic hepatitis D patients swiftly progress to cirrhosis and eventually 80% of the patients will develop cirrhosis, which is significantly higher than the percentage seen in patients only infected with HBV,” the authors wrote. They also noted that the reported incidence of HCC among chronic hepatitis D patients is much higher than that of patients infected with HBV alone.

Due to advances in the understanding of HDV virology, new therapeutic agents have been developed to target HDV life cycle at different stages. Bulevirtide, a subcutaneous lipopeptide, blocks the entry of HBV/HDV into hepatocytes. Lonafarnib, an oral agent, inhibits virion assembly in hepatocytes, reducing the HDV RNA. Another therapeutic under study is REP 2139, a nucleic acid polymer that also reduces serum HDV RNA levels.

“Recently, the infectious clones of HDV 1 to 8 and HBV envelope protein expression constructs of genotype A-H have been successfully established,” the authors wrote. “Based on this complete tool set, bulevirtide and lonafarnib, for the first time, were confirmed as potent and pangenotypic antiviral regimens against HBV/HDV or HDV.”

Further research is needed to increase the understanding ofthe possible origin of HDV, the authors noted. “The field is realizing the importance of understanding HDV epidemiology, which is the cornerstone of any effective public health response.”

—Rebecca Mashaw

Reference:

Miao Z, Xie Z, Ren L, Pan, Q. Hepatitis D: advances and challenges. Chin Med J.

2022;135(7):767-773.