hepatitis delta virus (HDV) is a major risk factor for hepatic decompensation
and liver-related death in people living with HIV, Spanish investigators report in
the online edition of Clinical Infectious
Diseases. Over an average of 80 months of follow-up, co-infection with hepatitis delta virus was
the single biggest risk factor for serious liver disease and death.
“Our study has the
lengthiest follow-up period of HIV-positive patients with chronic hepatitis
delta and provides a long-term perspective of its complications,” comment the
authors. “The results provide a unique insight about the natural history of
patients with HIV/HDV co-infection.”
approximately 15 million people have hepatitis delta virus. The virus can
only replicate within the context of chronic hepatitis B virus (HBV) infection.
However, hepatitis delta virus causes the most severe form of viral hepatitis, including rapid
progression of liver cirrhosis, decompensated liver disease and an increased
risk of liver cancer.
Investigators in Madrid
wanted to see how co-infection with hepatitis delta virus affected outcomes in people living with HIV.
designed a retrospective study involving 1147 people who received care after
On entry to the
study, 45% of participants had hepatitis C virus antibodies, 7% had chronic hepatitis C virus infection and
1.5% were infected with hepatitis delta virus. During follow-up, a total of 233 people with HIV and hepatitis C
co-infection received interferon-based therapy and 45% achieved a sustained
virological response. A total of 524 participants had HIV mono-infection.
The study endpoints
were progression to decompensated liver disease or death.
Most (81%) of the participants
in the study were men and the mean age was 42 years. Histories of
injecting drug use or
alcohol abuse were reported by 46% and 7%, respectively. At baseline,
85% of participants were taking HIV treatment and the mean CD4 count was
high at 566
followed for a mean of 81 months. During this time, 15 people died of
liver-related causes and 26 developed a first episode of decompensated liver
liver-related mortality rate was 3.6%. But the rates were much higher
among people with hepatitis delta virus infection and individuals who
had an unsuccessful response to hepatitis C virus therapy (14 and 8.6%,
The mean period of
survival for participants with HIV mono-infection was 101 months, which was
significantly longer than the 86 months (p < 0.001) observed in people with hepatitis D virus
co-infection and the 98 months for participants who did not respond to hepatitis C virus
therapy (p = 0.002).
patients with HIV mono-infection showed that co-infection with hepatitis delta virus was the
single biggest predictor of hepatic decompensation/death, increasing the risk
more than seven-fold (HR = 7.5; 95% CI, 1.84-30.8, p = 0.005). Baseline liver
stiffness was also a significant risk factor (HR = 1.1; 95% CI, 1.07-1.13, p
< 0.0001). A successful response to treatment for hepatitis C virus protected against disease
progression (HR = 0.11; 95% CI, 0.01-0.86, p = 0.03).
It is uncertain
how best to treat hepatitis delta virus. Protracted therapy with high-dose interferon
can have transient benefits, but it only rarely achieves complete viral
suppression. However, there is emerging evidence that long-term treatment with
tenofovir can reduce hepatitis delta virus replication and lessen liver damage.
The investigators therefore
recommend that all patients susceptible to hepatitis delta virus should
be vaccinated against hepatitis B virus
and that individuals with chronic hepatitis B should be screened for
hepatitis delta virus. The use of HIV/hepatitis B treatment regimens
that include tenofovir is also “encouraged.”