By Liz Highleyman

Over years of decades, chronic hepatitis B virus (HBV) infection can lead to severe liver disease including advanced fibrosis, cirrhosis, and hepatocellular carcinoma. There is considerable evidence that HIV positive people coinfected with hepatitis C virus (HCV) may experience accelerated liver disease progression, but less is known about outcomes in people with HIV-HBV coinfection.

At the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008) last week in Washington, DC, researchers from Portugal and Spain presented an analysis of fibrosis progression in HIV-HBV coinfected patients (detectable hepatitis B surface antigen, or HBsAg) treated with antiretroviral agents also active against HBV.

As background, the investigators noted that progression of fibrosis may be slowed or halted in most HIV-HBV coinfected individuals taking dually active agents as part of their HAART regimen. These include tenofovir (Viread) -- which was recently approved as a treatment for HBV as well as HIV -- lamivudine (3TC; Epivir), emtricitabine (Emtriva), and to a lesser extent, entecavir (Baraclude).

The study looked at a cohort of 80 HIV-HBV coinfected patients who underwent liver fibrosis assessment using the non-invasive transient elastometry method (FibroScan) since 2004. Metavir fibrosis estimates were defined as mild (F0-F2), moderate (F3), or severe (F4 or cirrhosis) for liver stiffness values < 9.5, 9.5-14, and >14 KPa, respectively. A second FibroScan was performed after a median interval of 24 months. Changes in liver stiffness, HBsAg and hepatitis B "e" antigen (HBeAg) seroconversion, liver-related complications, and mortality were assessed prospectively.

Most participants (86%) were men and the median age was 41 years. About two-thirds (64%) were also infected with HCV and 20% also had hepatitis delta virus (HDV) antibodies. About half had undetectable HBV DNA at the time of first FibroScan and 43% were HBeAg positive.

With regard to HAART, 92% were taking regimens containing lamivudine, emtricitabine, and/or tenofovir during the study period. The median time on HAART was about 5 years.

Results

• The initial liver fibrosis stage was mild in 66%, moderate in 14%, and severe in 20%.

• After a median follow-up period of 24 months, 5 patients (7.7%) experienced HBsAg seroconversion and 6 (23.1%) experienced HBeAg seroconversion.

• A second FibroScan could be obtained for 65 patients.

• Liver stiffness improved in 57% and worsened in 34%.

• Worsening liver stiffness was associated with:

• HDV coinfections (odds ratio [OR] 2.3);
• Greater CD4 cell recovery (OR 1.48 per 100 cells/mm3);
• Higher ALT levels at last FibroScan (OR 2.85).

• No episodes of liver-related complications or deaths were reported during the study period.

Based on these findings, the researchers concluded, "In HIV-HBV coinfected patients on anti-HBV active HAART, worsening in liver fibrosis was related with delta coinfection, greater ALT levels and, unexpectedly, with greater CD4+ gains, which might reflect immune reconstitution inflammatory responses."

Since almost all patients were taking dually active drugs, it was not possible to compare outcomes in those taking only anti-HIV drugs with no effect on HBV. Thus, it is difficult to say whether (or to what extent) these findings reflect the anti-HBV activity of antiretroviral drugs or HIV suppression and immune recovery due to HAART in general.

Hosp. Joaquim Urbano, Porto, Portugal; Hosp. Carlos III, Madrid, Spain.

11/04/08

Reference
T Teixeira, l Martin-Carbonero, P Barreiro, and others. Progression of Liver Fibrosis in HIV/HBV Coinfected Patients Undergoing Anti-HBV Active Antiretroviral Therapy. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-2315.