Hepatitis Delta Virus
Hepatitis D is caused by a defective RNA virus, hepatitis delta virus (HDV). Although HDV can replicate autonomously, it is dependent on hepatitis B virus (HBV) for its lipoprotein coat and complete virion assembly. Individuals with hepatitis D are always dually infected with HBV. HDV infection is rare in the United States. Among the persons who participated in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016 and had positive tests for HBV core antibodies and surface antigen, the estimated overall prevalence of HDV infection 0.11%. However, NHANES did not include high-risk populations, such as homeless and incarcerated persons. HDV prevalence may be higher among persons with injection drug use. In one cohort of persons who inject drugs HDV infection was identified in 35% of participants with chronic HBV infection.
HDV has two clinical patterns of infection: coinfection, in which exposure to HDV and to HBV occurs simultaneously; and superinfection, in which acute HDV infection occurs in a person with chronic HBV infection. HDV coinfection is usually clinically indistinguishable from acute hepatitis B infection. It is often transient and self-limited. Acute liver failure may occur in injection drug users.
HDV superinfection of a chronic HBsAg carrier more often presents as severe acute hepatitis in a previously unknown HBV carrier or as an exacerbation of preexisting chronic hepatitis B infection. Most of these patients progress to chronic HDV infection.
Diagnosis of HDV relies on detection of HDV antigen, HDV IgM, or HDV total antibodies (combined IgM and IgG) in the sera of infected patients. Anti-HDV IgM typically appears in serum at 2 to 3 weeks after onset of symptoms and disappears by 2 months after acute HDV infection, but it may persist up to 9 months in HDV superinfection. HDV IgG and HDV total antibodies persist in serum after resolution of acute HDV infection and in chronic coinfection.
HBV DNA level is more commonly elevated in patients with acute coinfection than in patients with superinfection. HBV DNA levels can be quite low in superinfection because of an anti-HDV immune response. HDV RNA is detected early but is transient during HBV and HDV coinfection.
The serological patterns of hepatitis D virus testing in different clinical settings are summarized in the following table.
| Serologic Test | Acute Coinfection | Acute Superinfection | Chronic Infection |
| HBsAg | Positive | Positive | Positive |
| HBc IgM | Positive | Negative | Negative |
| HDV Ag | Positive early | Positive early | Negative |
| HDV RNA | Positive early | Positive | Positive |
| HDV Total Ab | Late, low titer | Positive | Positive |
| HDV IgM | Positive early | Positive | Positive |
References
Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet 2011;378:73-85.
Koh C, Heller T, Glenn JS. Pathogenesis of and new therapies for hepatitis D. Gastroenterology 2019;156(2):461-476.e1.
Njei B, Do A, Lim JK. Prevalence of hepatitis delta infection in the United States: National Health and Nutrition Examination Survey, 1999-2012. Hepatology 2016;64:681-682.
Olivero A, Smedile A: Hepatitis delta virus diagnosis. Semin Liver Dis 2012;32:220-227
Pascarella S, Negro F: Hepatitis D virus: an update. Liver International 2011;31(1):7-21
