Hepatitis D is caused by a defective RNA virus (delta agent) that can replicate only in the presence of hepatitis B virus. It occurs, uncommonly, as a coinfection with acute hepatitis B or as a superinfection in chronic hepatitis B.
(See also Causes of Hepatitis, Overview of Acute Viral Hepatitis, and Overview of Chronic Hepatitis.)
Hepatitis D is usually transmitted by parenteral or mucosal contact with infected blood or body fluids. Infected hepatocytes contain delta particles coated with hepatitis B surface antigen (HBsAg).
Prevalence of hepatitis D virus (HDV) varies widely geographically, with endemic pockets in several countries (1). Parenteral illicit drug users are at relatively high risk, but HDV, unlike hepatitis B virus (HBV), has not widely permeated the MSM (men-who-have-sex-with-men) community.
The two recognized forms of HDV infection are coinfection (simultaneous acquisition of HBV and HDV in a person with no prior HBV exposure) and superinfection (HDV acquisition in a person with pre-existing chronic HBV infection). Hepatitis B (HBV)-HDV coinfection is most often self-limited, while superinfection of chronic hepatitis B with hepatis D usually results in chronic HBV-HDV infection (2).
General references
1. Asselah T, Rizzetto M. Hepatitis D Virus Infection. N Engl J Med. 2023;389(1):58-70. doi:10.1056/NEJMra2212151
2. Negro F, Lok AS. Hepatitis D: A Review. JAMA. 2023;330(24):2376-2387. doi:10.1001/jama.2023.23242
Symptoms and Signs of Hepatitis D
Hepatitis D infection typically manifests as:
Unusually severe acute hepatitis B virus (HBV) infection (coinfection)
An acute exacerbation in chronic HBV carriers (superinfection)
A relatively aggressive course of chronic HBV infection
Diagnosis of Hepatitis D
If hepatitis B infection is confirmed, anti-HDV antibody as initial screening test followed by serum HDV RNA reverse transcriptase-polymerase chain reaction (RT-PCR) for confirmatory testing
If serologic tests for hepatitis B confirm infection and clinical manifestations are severe, antibody to hepatitis D virus (HDV) (anti-HDV) antibody levels should be measured as an initial screening test (1). Positive anti-HDV implies prior exposure to HDV, but does not confirm active infection. Furthermore, in acute infection, anti-HDV may not become detectable until weeks after the acute illness. If anti-HDV is positive, HDV RNA testing should be performed to confirm active infection.
Diagnosis reference
1. Asselah T, Rizzetto M. Hepatitis D Virus Infection. N Engl J Med. 2023;389(1):58-70. doi:10.1056/NEJMra2212151
Treatment of Hepatitis D
Supportive care
For HBV-HDV coinfection, pegylated interferon-alfa and sometimes bulevirtide
Hepatitis B should be treated independently from hepatitis D. Antiviral therapy with nucleoside/nucleotide analogues (eg, entecavir, tenofovir) should be considered to suppress HBV replication, though these agents have no direct activity against HDV itself. For chronic HDV infection, pegylated interferon-alfa is recommended for at least 48 weeks (1). Pegylated interferon-alfa is contraindicated in patients with decompensated liver disease. Bulevirtide, an entry inhibitor that blocks HDV from entering hepatocytes (available in Europe and the United States, and some other countries) is sometimes used both in combination with pegylated interferon-alfa or as monotherapy. Several other agents are in trials or development (2, 3).
Alcohol should be avoided, as it can accelerate liver damage. Restrictions on diet or activity, including commonly prescribed bed rest, have no established scientific basis.
Treatment references
1. Kushner T, Cohen SM, Ahn J, et al. AGA Clinical Practice Update on Management of Hepatitis Delta: Commentary. Gastroenterology. 2025;169(5):1063-1069. doi:10.1053/j.gastro.2025.07.037
2. Asselah T, Rizzetto M. Hepatitis D Virus Infection. N Engl J Med. 2023;389(1):58-70. doi:10.1056/NEJMra2212151
3. Asselah T, Chulanov V, Lampertico P, et al. Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D. N Engl J Med. 2024;391(2):133-143. doi:10.1056/NEJMoa2314134
Prevention of Hepatitis D
No product exists for immunoprophylaxis of hepatitis D. However, prevention of HBV infection prevents HDV infection.
Key Points
Hepatitis D occurs only with hepatitis B.
Suspect hepatitis D particularly when cases of hepatitis B are severe or when symptoms of chronic hepatitis B are worsening.
Treat hepatitis B with nucleoside/nucleotide analogues (entecavir or tenofovir) when indicated, and treat hepatitis D with pegylated interferon-alfa and sometimes other medications (eg, bulevirtide).
Prevent infection as for hepatitis B.
Drug Information for the Topic
