Co-infection with hepatitis delta increases risk of death for patients with HIV and chronic hepatitis B

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 the infection.

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 (HBV).

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 < 0.001).

Hepatitis delta co-infection was more common in Southern (21%) and Eastern Europe (9%) than in Northern (9%) or Central Europe (11%) (p = 0.003).

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 < 0.01).

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 infection.

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 = 0.008).

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 virus.

“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.”