Hepatitis Delta Infection May Worsen Disease Progression in HIV-HBV Coinfected Individuals

By Liz Highleyman

Hepatitis Delta Virus Image

Hepatitis delta virus (HDV) -- which occurs only in conjunction with hepatitis B virus (HBV) -- has been associated with worse liver disease outcomes in studies of HIV negative individuals.

HDV in HIV Positive Patients

As described in the April 1, 2007 issue of Clinical Infectious Diseases, researchers from National Taiwan University Hospital conducted a study to assess the influence of HDV infection on responses to highly active antiretroviral therapy (HAART) and hepatic complications in HIV-HBV coinfected patients.

Between January 1995 and June 2003, the authors identified 26 HDV-infected HIV positive case patients and 78 matched HIV positive HDV-uninfected control subjects. They assessed clinical and immunological outcomes, HBV and HIV viral loads, and genotypic resistance of HBV to lamivudine (Epivir).

Results

• HDV-infected case patients had a higher rate of injection drug use (7.7% vs 1.3%; P = 0.05) and lower baseline serum HBV DNA levels (median 4.04 vs 5.75 log10 copies/mL; P = 0.07) than HDV-uninfected control subjects.

• Over a median observation period of 54.7 months, HDV infection did not have an adverse impact on clinical, virological, or immunological responses to HAART.

• However, HDV-infected patients had a higher incidence of:

- hepatitis flares (57.7% vs 23.1%; P = 0.002);
- hyperbilirubinemia (34.6% vs 14.1%; P = 0.04);
- liver cirrhosis (26.9% vs 5.1%; P = 0.009);
- hepatic decompensation (23.1% vs 5.1%; P = 0.007);
- death (adjusted hazard ratio 5.41; P = 0.02).

• Conversely, HDV-infected patients had a lower risk of genotypic resistance to lamivudine (0% vs 57.1%; P = 0.003).

"HDV infection did not affect clinical, virological, or immunologic responses to highly active antiretroviral therapy in patients with HBV-HIV coinfection," the authors concluded. "HDV infection increased risk of hepatitis flares, liver cirrhosis, hepatic decompensation, and death in patients with HBV-HIV coinfection."

HDV Epidemiology

In a related letter in the May 2007 issue of Hepatology, Heiner Wedemeyer and colleagues from Medizinische Hochschule in Hannover, Germany, responded to a previous editorial by Patricia Farci, which noted that the prevalence of HDV infection among HBsAg-positive individuals had declined dramatically in Italy in the 1990s.

In contrast, they wrote, hepatitis delta is not a "vanishing disease" in other countries in Europe, mainly due to immigration of people from high endemic areas.

In an analysis of serum samples from 2354 consecutive HBsAg-positive patients tested at the authors' hospital between 1992 and 2006, 253 samples (11.3%) tested positive for antibodies to HDV. For 144 individuals with known countries of birth, 19% of HDV-infected patients were born in Germany, whereas 26% had immigrated from Turkey and 28% from Eastern Europe or countries of the former Soviet Union. The percentage testing positive for HDV declined from 18.6% in 1992 to 6.8% in 1997, but there was no further decline between 1997 and 2006.

"[O]ur data clearly demonstrate that HDV infection in Europe is no longer a disease found only in the Mediterranean area, but also has become an important clinical consideration in central Europe," the authors wrote.

In her reply, Farci acknowledged that HDV may not be "vanishing" in several European countries; in France, she noted, an analysis of 617 patients found that HDV prevalence was not as high among Eastern European immigrants as it was in the German study, but was most often seen among African immigrants.

Given this variability in HDV prevalence, they urged clinicians to test patients with HBV at least once for HDV.

Treatment of Patients with HDV

Finally, Wedemeyer and colleagues presented data from the Hep-Net/International Delta Hepatitis Intervention Trial (HIDIT-1), a study of treatment of 90 HBV patients with HDV, at the 42 Annual Meeting of the European Association for the Study of Liver Diseases (EASL) last month.

They found that pegylated interferon alfa-2a (Pegasys) reduced HDV RNA levels by at least 2 log10 in about 40% of patients. Further, 25% had undetectable HDV RNA after 48 weeks of therapy, and 27% remained HDV negative 24 weeks after the end of treatment. Adefovir (Hepsera) did not affect HDV replication -- although it did reduce HBV DNA levels -- and combining Pegasys with adefovir did not produce greater HDV suppression.

05/25/07

References

WH Sheng, CC Hung, JH Kao, and others. Impact of hepatitis D virus infection on the long-term outcomes of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. Clinical Infectious Diseases 44(7): 988-985. April 1, 2007.

H Wedemeyer, B Heidrich, and MP Manns. Hepatitis D virus infection - Not a vanishing disease in Europe! Hepatology 45(5):1331-1332. May 2007.

H Wedemeyer, C Yurdaydin, G Dalekos, and others. A Multicenter Randomised Study Comparing the Efficacy of Pegylated interferon-alfa-2a plus Adefovir dipivoxil vs. Pegylated interferon-alfa-2a plus Placebo vs. Adefovir dipivoxil for the Treatment of Chronic Delta Hepatitis: The HIDIT-1 Study. 42nd Annual Meeting of the European Association for the Study of the Liver (EASL). Barcelona, Spain. April 11-15, 2007.

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