Author: Karen Blum
The prevalence of hepatitis D virus (HDV) in the United States may be higher than clinicians realize, a new study has found.
“We need to do a better job of understanding the epidemiology of hepatitis D in the U.S. and really get at the question of who is currently infected, because we need that information to inform screening guidelines as treatments are being developed,” stressed the study’s lead author, Eshan Patel, MPH, a biostatistician with the Department of Pathology at Johns Hopkins Medicine in Baltimore.
Hepatitis D, or delta, virus is a defective human RNA virus that requires surface antigen of hepatitis B virus (HBsAg) for transmission and persistence. Compared with having HBV infection alone, coinfection with HDV is associated with increased progression to cirrhosis, liver cancer, end-stage liver disease and death. Although there is a vaccine to protect against HBV—in turn, protecting against HDV—both hepatitis infections are still prevalent in the United States, according to Mr. Patel.
Trends in Testing
Testing for HDV is rarely conducted in the United States, he said. The American Association for the Study of Liver Diseases (AASLD) recommends testing only for HBsAg carriers at high risk for HDV infection. By contrast, the European Association for the Study of the Liver (EASL) and the Asian Pacific Association for the Study of the Liver both recommend routine testing for HDV among all HBsAg-positive patients. “Given the high prevalence of antibodies for hepatitis D among HBsAg carriers in this national population-based study, adopting a similar testing strategy in the U.S. should be considered,” Mr. Patel said.
Among the HBsAg-positive adults, a higher proportion of those with antibodies to HDV reported being diagnosed with liver disease (30%) compared with those without antibodies to the virus (9%).
This study’s estimates for HDV prevalence may be inflated, said Christopher Koh, MD, MHSc, an associate research physician with the Liver Diseases Virology Section of the National Institute of Diabetes and Digestive and Kidney Diseases. “It’s estimated that about 10% of all patients with hepatitis B likely will have hepatitis D, so the findings they had were a bit surprising—a lot higher than we would expect.” It could result from the study sample being relatively small, he said.
Still, practitioners should be concerned about HDV because it has been considered the most aggressive and virulent chronic viral hepatitis known to infect humans, said Dr. Koh, who also directs the institute’s gastroenterology and hepatology fellowship programs.
Treatment for HDV
There are no FDA-approved therapies for HDV, but societies such as AASLD and EASL recommend a one-year course of interferon-based therapy, according to Dr. Koh. Most physicians use pegylated interferon, “but the response rates are in general pretty abysmal,” he said. “About 20% to 25% of patients will respond to it. Once therapy is discontinued, most relapse. People are hunting for different types of therapies for delta hepatitis.”
Three main investigational drugs are still in clinical trials, according to a recent paper Dr. Koh co-authored (Gastroenterology 2019;156:461-476.e1). One is lonafarnib (Eiger BioPharmaceuticals), an agent that inhibits the prenylation process required for HDV packaging and secretion. The others are REP2139 (Replicor), a nucleic acid polymer that inhibits the secretion of HBsAg, and myrcludex B (MYR Pharma), which targets the liver protein NTCP, blocking the virus’s entry mechanism into liver cells. The only U.S.-based trials at this time are with lonafarnib. However, future studies evaluating all three agents are being planned, Dr. Koh said.
Meanwhile, Dr. Koh said he agrees with Mr. Patel’s call for additional screening: “Clearly, there just aren’t enough patients being tested for delta hepatitis.”