Hepatitis B: Nucleoside analogues slow liver fibrosis progression

Nucleoside analogues slow liver fibrosis progression in chronic hepatitis B

Last Updated: 2010-12-10 11:02:03 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Nucleoside/nucleotide analogues as part of an anti-HIV regimen slow the progression of liver fibrosis in patients coinfected with hepatitis B (HBV), researchers from Spain report online in the January 2, 2011 issue of AIDS

Nucleoside/nucleotide analogues often form a part of highly active antiretroviral therapy (HAART) for HIV, but whether prolonged use of these agents influences the long-term markers of liver disease in patients coinfected with both viruses hasn't been studied before now.

Dr. Luz Mart�n-Carbonero and colleagues from Hospital Carlos III, Madrid, evaluated the long-term clinical outcomes, HBsAg and/or HBeAg clearance, and changes in liver stiffness (a measure of liver fibrosis) in 92 patients with HIV-HBV coinfection, most of whom were treated with lamivudine/emtricitabine (94%) and/or tenofovir (82%) and all of whom received at least one drug with dual activity against both viruses.

At the end of follow-up, serum HBV-DNA was undetected in 65 of 73 patients (89%).

Seven of the 42 patients who were HBsAg-positive at baseline cleared serum HBsAg (2.6/100 patient-years), and 5 of these 7 had anti-HBs seroconversion. The only 2 patients who cleared HBsAg but didn't seroconvert were coinfected with HDV but cleared their serum HDV-RNA and were positive for anti-HCV antibodies (without detectable HCV-RNA).

Investigators say these clearance rates compare with rates lower than 2% among HBV-monoinfected carriers when using oral nucleoside/nucleotide analogues and with rates around 2.6% in HIV-HBV coinfected individuals receiving similar treatment.

Eleven of 42 serum HBeAg-positive patients cleared HBeAg (9/100 patient-years), but only 5 showed anti-HBe seroconversion.

These HBeAg clearance rates compared with rates of 12 to 21% among HIV-negative patients and with yearly rates of 9% in HIV-HBV coinfected individuals.

Six patients died during follow-up (2.2/100 patient-years), and 8 experienced at least one episode of liver decompensation (2.9/100 patient-years).

Overall, median liver stiffness declined slightly during 40.1 months of follow-up, but the change was not significant. The proportion of patients with null-mild liver fibrosis, however, increased significantly from 47.8% at baseline to 64.7% at follow-up.

About three-quarters of the patients stayed at their original liver fibrosis stage, whereas 9 patients improved from moderate-advanced to null-mild fibrosis, 2 from cirrhosis to moderate-advanced fibrosis, and 1 from cirrhosis to null-mild fibrosis. Four patients worsened from null-mild to moderate-advanced fibrosis, and 2 worsened from moderate-advanced fibrosis to cirrhosis.

The only independent predictors of cirrhosis in multivariate analysis were positive anti-HCV antibody and low CD4 cell counts. No single variable was associated with a worsening or improvement of liver fibrosis.

"Although our data strongly suggest that long-term control of HBV replication with potent anti-HBV active antiretroviral regimens may slow down liver fibrosis progression in HIV-HBV coinfected patients, patients with low CD4 cell counts and those with positive serum HCV antibody seem to remain at increased risk for developing cirrhosis," researchers say.

"Of note, liver cancer may develop in this setting even in the absence of cirrhosis, as in one of our patients, and, therefore, periodic screening for this tumor with periodic assessment of alphafetoprotein and abdominal ultrasound is warranted."

SOURCE: http://link.reuters.com/xaz59q

AIDS 2011;25:73-79.