Research Highlights Need to Increase Screening and Treatment of Hepatitis Delta Virus

Hepatitis D is one of the five common types of hepatitis, which are viral infections of the liver. Importantly, only individuals already infected with the hepatitis B virus (HBV) can acquire hepatitis D.

Although only 5% of patients with chronic HBV infection have been diagnosed with HDV, this virus is of high clinical importance because it is associated with a significant increase in risk of liver-related complications compared with patients with chronic HBV infection alone. For example, current data suggest that chronic HDV increases the risk of liver cirrhosis, liver failure, and liver cancer two- to three-fold compared with chronic HBV. Other research suggests approximately 70% of patients with chronic HDV develop cirrhosis within 10 years of diagnosis.

In our recent study of U.S. veterans with HBV, we found that nearly one in three individuals had already developed advanced liver disease at the time of their HDV diagnosis. We need more effective screening programs nationwide to help patients receive earlier diagnoses and connect them to treatments that can prevent liver-related complications.

Routine testing for HDV infection has been limited due to a combination of factors, including the absence of clinical guidelines, inconsistent payer coverage of HDV testing, and inconsistent availability of laboratory tests. In addition, both clinicians and patients have low awareness of HDV.

Research suggests clinicians should carefully consider screening for HDV in all patients with chronic HBV, especially those with elevated liver enzymes despite inactive or treated HBV. Clinicians need to recognize that more than one in five patients with chronic HDV infection do not have any of the established risk factors that would typically prompt screening.

Emerging research over the past five years has provided increased evidence for universal HDV reflex testing, paired with HBV screening. A paper published earlier this year suggests that universal HDV screening may be cost-effective and decrease HDV-related cirrhosis, liver cancer, and HDV-related death.

Within our clinical program, HDV screening is considered the standard of care for all patients with an established diagnosis of chronic HBV infection, and HDV antibody testing is performed at the time of initial consultation.

While there are highly effective antiviral medications used to treat HBV, those medications do not have any effect on HDV. Currently, there are no U.S. Food and Drug Administration (FDA)-approved medications for HDV; however, clinical guidelines recommend the off-label use of pegylated interferon-alfa as a first-line therapy. Due to the poor efficacy and tolerability profile of this medication, there remains a significant unmet medical need for better treatments for HDV.

Fortunately, there are at least three antiviral regimens in clinical trials for HDV. One antiviral regimen has completed Phase III trials and has recently been approved in Europe by the European Medicines Agency and is awaiting possible approval by the U.S. FDA. We will offer two research protocols evaluating novel antiviral agents for HDV here at Yale.

Although we await approved treatments, we remain hopeful that increased research and awareness of HDV will lead to progress in screening, diagnosing, and caring for patients earlier, ultimately improving patient outcomes.