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Hepatitis Delta Found in 15% of HIV/HBV Coinfected People, Increases Risk of Death

Approximately 15% of people with HIV who test positive for hepatitis B surface antigen (HBsAg) also carry hepatitis delta virus (HDV), a defective virus that can only replicate in the presence of hepatitis B virus (HBV) but can lead to more severe liver damage, according to a recent European study.alt

As described in the August 19, 2011, advance online edition of AIDS, Vincent Soriano and fellow investigators with the EuroSIDA study aimed to learn more about the prevalence, epidemiology, virological profile, and natural history of hepatitis delta in HIV positive people.

HDV is a blood-borne virus like HBV and HIV, suggesting that injection users infected via shared syringes or other injection equipment might be at high risk of having HDV as well.

Out of more than 16,000 HIV positive individuals enrolled in the EuroSIDA cohort, the investigators identified 1319 (7.9%) who had ever tested positive for HBsAg, indicating exposure. The body often clears HBV on its own without treatment, so many HBsAg positive people do not have current active hepatitis B.

During the latest follow-up visit, 1084 participants (6.5%) were currently HBsAg positive. The HDV sub-study included 422 of these patients who had available stored blood samples. The researchers tested samples for HDV using a commercial enzyme immunoassay and measured HDV RNA viral load using real-time PCR.


  • 61 out of the 422 tested HIV/HBsAg positive patients also carried HDV antibodies, a prevalence of 14.5%.
  • HDV was primarily seen among injection drug users, who are concentrated in Southern and Eastern Europe:
    • Russia and Eastern Europe: HDV prevalence 25%;
    • Southern Europe including Italy and Spain: 21%;
    • Central Europe, including France and Southern Germany: 11%;
    • Northern Europe, including the U.K., Scandinavia, and Northern Germany.
  • 87.0% of participants who tested positive for HDV antibodies had detectable HDV RNA -- indicating active viral replication -- with a median viral load of 1.76 x 107 copies/mL.
  • Overall, people triply infected with HDV had lower serum HBV DNA viral load than HBsAg positive people without hepatitis delta.
  • This inhibitory effect of HDV on HBV replication was not seen, however, in people with HBV genotype D.
  • HDV triple infection was not associated with more rapid progression to AIDS.
  • HDV was, however, significantly associated with a higher risk of death due to liver-related causes and overall mortality.

The study authors concluded that most patients infected with HDV "exhibit detectable HDV viremia," and that "[v]iral interference between HBV and HDV is manifest in all but HBV genotype D carriers, in whom overt co-replication of both viruses occurs, which might result in enhanced liver damage."

"Treatment of chronic hepatitis delta is a huge challenge," they explained in their discussion. HDV replicates using a human polymerase enzyme, so nucleoside/nucleotide analog drugs designed to inhibit viral polymerases do not block HDV replication. Current recommended therapy is pegylated interferon-alfa (Pegasys or PegIntron) for at least 12 months. Some studies suggest that the most potent nucleoside/nucleotide analogs, such as tenofovir (Viread), may be beneficial for a subset of hepatitis delta patients, though this has mainly been limited to people with HBV genotype A or hepatitis B "e" antigen (HBeAg).

"Most guidelines recommend that all HBsAg [positive] patients should be tested for anti-HDV antibodies," the researchers wrote. "Given that a fraction of HDV-seropositive individuals may not actively replicate the virus, serum HDV RNA should be measured and treatment be considered in patients with detectable viremia, given that chronic hepatitis delta is associated with a high risk of cirrhosis in HIV-infected patients...Failure to exclude HDV infection in HBsAg carriers may result in an unexpected worse outcome and trigger unnecessary search for other etiologies of liver disease."

Investigator affiliations: Infectious Diseases, Hospital Carlos III, Madrid, Spain; University College London Medical School, Royal Free Campus, London, UK; Clinica Malattie Infettive e Tropicali, Milan, Italy; Infectious Diseases Department, Hospital for Infectious Diseases, Warsaw, Poland; Infectious Diseases Department, Western General Hospital, Edinburgh, UK; Infectious Diseases Department, Hospital Santa Maria, Lisbon, Portugal; Infectious Diseases Department, St Pierre Hospital, Brussels, Belgium; Copenhagen HIV Programme, Copenhagen, Denmark; Infectious Diseases Department, Rigshospitalet, Copenhagen, Denmark; Infectious Diseases Department, Bonn University Hospital, Bonn, Germany.



V Soriano, D Grint, A d’Arminio Monforte, et al. Hepatitis delta in HIV-infected individuals in Europe. AIDS (abstract). August 19, 2011 (Epub ahead of print).