NIH
Zebra of the Week: Hepatitis D virus (HDV) infection
Hepatitis D virus (HDV) infection—also known as delta hepatitis—is a rare but highly virulent form of viral hepatitis that occurs only in the presence of hepatitis B virus (HBV). HDV is a defective RNA “satellite” virus that depends on HBV for replication and transmission, making coinfection or superinfection with HBV a prerequisite for disease.
Clinically, HDV infection is notable for its severity and unpredictable course. Patients may present with anything from mild acute hepatitis to fulminant liver failure; however, the disease more commonly progresses to severe liver injury, hepatic decompensation, and rapid progression to cirrhosis. Coexisting HBV infection markedly amplifies morbidity, with an elevated risk of hepatocellular carcinoma compared with HBV monoinfection.
Two clinical patterns are recognized: HBV–HDV coinfection (simultaneous acquisition) and superinfection (HDV infection in a patient already chronically infected with HBV). Coinfection typically produces an acute, sometimes severe illness but is often self-limited, whereas superinfection is more likely to result in chronic HDV infection and accelerated liver disease, including cirrhosis and liver failure. Symptoms are similar to other viral hepatitides—fatigue, jaundice, abdominal pain, nausea, and dark urine—but tend to be more severe than in HBV alone.
Epidemiologically, HDV is uncommon in the US but remains underdiagnosed; estimates suggest tens of thousands of affected individuals, largely among patients already infected with HBV. Transmission parallels HBV, occurring via blood or body fluids, including injection drug use, sexual contact, and perinatal exposure. Importantly, HBV vaccination confers indirect protection against HDV by preventing the necessary helper infection.
Historically, treatment options for HDV have been limited and suboptimal, with pegylated interferon offering modest and often transient virologic responses.
In May 2026, FDA approved Hepcludex (bulevirtide-gmod), the first therapy for chronic HDV infection. This entry inhibitor blocks the NTCP receptor on hepatocytes, preventing viral entry. In the pivotal phase 3 MYR301 trial, nearly half of treated patients achieved a combined virologic and biochemical response at 48 weeks, compared with 2% in controls.
Sources:
NIH GARD. Hepatitis D virus infection
CDC. Hepatitis D Basics
Gish RG, et al. (2023, October). Gastroenterol Hepatol. Delta Hepatitis in the United States: Epidemiology, Testing, and Linkage to Care