The American Gastroenterological Association (AGA) has released a Clinical Practice Update on the management of hepatitis delta virus (HDV) infection, providing current guidance on epidemiology, screening, diagnosis, and treatment.
Hepatitis delta virus occurs in patients with hepatitis B virus (HBV) infection and substantially increases the risk of cirrhosis, hepatocellular carcinoma, and liver-related mortality compared with HBV monoinfection. Recent analyses estimate that approximately 30,000 to 60,000 people in the United States have active HDV infection.
Among those with chronic hepatitis B, prevalence varies across groups, with 4.2% among non–US-born patients, 6.7% among people with HIV coinfection, 43.8% among persons who inject drugs, and 5.1% among men who have sex with men. A recent meta-analysis found that concurrent HDV infection nearly doubles the risk of compensated cirrhosis and increases the risk of decompensated cirrhosis, hepatocellular carcinoma, and liver-related death by up to fourfold.
Testing for HDV remains limited in the United States. Among more than 40,000 veterans with positive hepatitis B surface antigen, only about 11% were tested for HDV, and few received confirmatory RNA testing. Even in populations with high-risk features, HDV screening rates have not improved significantly over the past decade, noted Tatyana Kushner, MD, (Division of Gastroenterology and Hepatology, Weill Cornell School of Medicine, New York, NY) and colleagues, in the published article in Gastroenterology.
In line with the World Health Organization’s 2024 guidance, the AGA panel recommended universal HDV screening for all patients with chronic HBV infection. Screening should begin with anti-HDV antibody testing, followed by confirmatory HDV RNA polymerase chain reaction testing to identify active infection.
Patients with HDV infection should be evaluated for cirrhosis using noninvasive methods such as vibration-controlled transient elastography or FIB-4, both of which show high diagnostic accuracy. Given the elevated risk of hepatocellular carcinoma, all patients with HDV should be enrolled in liver cancer surveillance programs.
Pegylated interferon-alpha remains the only approved treatment for chronic HDV in the United States. Sustained virologic response rates range from 23% to 57%, and relapse occurs in about half of patients after discontinuation. Despite these limitations, responders show improved survival and reduced liver-related complications. Several new therapeutic agents are in late-stage clinical trials.
Bulevirtide, a viral entry inhibitor, has been approved in Europe since 2020 and achieved response rates of 45% to 48% at 48 weeks in phase 3 trials; an expanded access program is available in the US. Brelovitug, a monoclonal antibody targeting hepatitis B surface antigen, showed a 67% HDV RNA decline at 24 weeks in phase 2 data. A combination therapy of tobevibart and elebsiran achieved approximately 50% alanine aminotransferase normalization and a 2-log or greater HDV RNA decline in all treated participants at 24 weeks. Lonafarnib, an oral farnesyltransferase inhibitor, produced response rates of 10% to 19% at 48 weeks, and nucleic acid polymers such as REP2139 demonstrated a 73% HDV RNA decline in early trials.
"The concurrent development of novel therapeutics with increased efficacy and safety will hopefully improve disease outcomes in patients living with HDV," wrote Dr. Kushner and colleagues. "As promising HDV treatments enter phase 3 trials and in particular drugs that also target functional cure of HBV are developed, the future will hopefully bring curative treatments for HDV that can decrease disease burden and optimize outcomes for patients living with HDV."
Source: Gastroenterology
