Infection with hepatitis delta virus is associated with an
increased risk of death for HIV-positive patients with chronic hepatitis B
infection, European research published in the online edition of AIDS shows.
“In our study we reported for the first time that hepatitis
delta was…predictive of increased risk of liver-related death and overall
mortality in HIV patients,” write the investigators, who recommend that all
HIV-positive patients with chronic hepatitis B infection should be tested for
Hepatitis delta (HDV) is the most aggressive form of chronic
hepatitis infection in humans. Worldwide, between 15 and 20 million individuals
carry the virus, including 5% of patients with chronic hepatitis B virus infection
HIV, hepatitis B, and hepatitis delta all share modes of
transmission, including sex transmission, injecting drug use and from a mother
to her baby.
However, little information is available on the prevalence
of the infection in patients with HIV. Nor are its epidemiology, viral
characteristics, and natural history well understood.
To answer these questions investigators from the EuroSIDA
cohort examined the medical records of HIV-positive patients with chronic
hepatitis B (hepatitis B surface antigen positive [HBsAg+]).
Their analysis included 422 patients and 61 (15%) had
antibodies to hepatitis delta.
Prevalence of the infection was significantly higher in
patients with a history of injecting drug use (42%) compared to patients whose
HIV risk factor was heterosexual intercourse (9%) or sex between men (3%) (p
Hepatitis delta co-infection was more common in Southern
(21%) and Eastern Europe (9%) than in Northern (9%) or Central Europe (11%) (p
Most of the hepatitis delta-infected patients were white
(84%) and two-thirds were receiving antiretroviral therapy. Median CD4 cell
count was 281 cells/mm3 and median HIV viral load was undetectable.
The investigators’ first set of analyses showed that
co-infection with hepatitis delta was significantly associated with younger age
(p = 0.0007), female sex (p = 0.005), intravenous drug use (p < 0.0001),
co-infection with hepatitis C virus (p < 0.0001), residence in Southern or
Eastern Europe (p < 0.003), and infection with hepatitis B sub-type D (p
However, only injecting drug use (p = 0.0003) remained
significant in analysis that controlled for confounding factors.
Hepatitis B genotype D was detected in 50% of patients
infected with hepatitis delta compared to 12% of individuals negative for the
The investigators were able to detect hepatitis delta viral
load in 31 patients, and median viral load was 1.76 x 107 copies/ml.
The only hepatitis B subtype found in patients with a
hepatitis delta viral load above this level was subtype D.
Earlier research has shown that, with the exception of
patients with hepatitis B subtype D, co-infection with hepatitis delta is
associated with an attenuation of hepatitis B virus infection. The present
study confirmed these findings. Overall, co-infected patients had lower median
hepatitis B viral loads than patients not infected with hepatitis delta (p =
0.003). However, the exception was patients with hepatitis B genotype D.
“Hypothetically, this last group of patients replicating
both HBV and HDV might experience enhanced liver damage,” suggest the investigators.
Co-infection with hepatitis delta was associated with an
increased risk of death (p = 0.01) and of death from end-stage liver disease (p
Treatment for hepatitis delta is “challenging” and usually
consists of twelve months of therapy with pegylated interferon-alpha. There is
also some evidence that tenofovir, 3TC and adefovir are active against the
“Most guidelines recommend that HBsAg+ patients should be
tested for anti-HDV antibodies,” note the authors, “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.”