Hepatitis delta virus co-infection increases risk of poor liver-related outcomes for people living with HIV

Michael Carter
07 April 2014

Co-infection with 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.”

Worldwide, 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.

They therefore designed a retrospective study involving 1147 people who received care after 2004.

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 cells/mm3.

Participants were 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 disease.

The overall 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%, respectively).

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).

Comparison with 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.”


Fernándes-Montero JV et al. Hepatitis delta is a major determinant of liver decompensation events and death in HIV-infected patients. Clin Infect Dis, online edition ahead of print, 2014.