Liver Fibrosis Increases the Risk of Antiretroviral Drug Toxicity

Liver toxicity is a potential concern related to antiretroviral therapy, and research suggests that the risk is higher in patients with pre-existing liver disease, including chronic hepatitis B or C.

As reported at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), Italian researchers evaluated the relationship between liver fibrosis and the rate of HAART-associated liver toxicity.

The study included HIV positive patients, mostly men (68%), with a mean age of 44 years. About half (54%) were coinfected with HCV and 7% with HBV. Most were taking some form of combination antiretroviral therapy. Subjects were divided into 4 groups:

• HIV monoinfected, antiretroviral-naive (n = 19);

• HIV monoinfected, on HAART (n = 132);

• HIV-HCV coinfected, antiretroviral-naive (n = 21);

• HIV-HCV coinfected, on HAART (n = 177).

Study participants underwent non-invasive fibrosis assessment using FibroScan (transient elastography, a method of measuring liver "stiffness"). Liver fibrosis was staged using a scoring system of F0 (no fibrosis) to F4 (cirrhosis).

Hepatotoxicity was defined as an increase in AST or ALT levels over 5 times the upper limit of normal -- or a 3-5 fold increase if baseline levels were already elevated -- occurring in the past 3 years. The occurrence of hepatotoxicity was assessed in relation to liver fibrosis stage, antiretroviral regimen, and amount of time on HAART.

Results

• Overall, there were 18 episodes of hepatotoxicity (4.6%).

• All these events were asymptomatic and did not lead to changes in therapy.

• There was no association between liver toxicity and age, sex, transmission risk category, CD4 cell count, or HIV viral load.

• There was also no significant association between liver toxicity and use of specific antiretroviral drugs or regimens.

• HIV-HCV coinfected patients had a more advanced fibrosis stage (F3-F4) compared with HIV monoinfected subjects (P = 0.001).

• There was no association between fibrosis stage and HAART use.

• Patients with advanced fibrosis (F3-F4) had a greater rate of hepatotoxicity than those with mild-to-moderate fibrosis (F1-F2) (P < 0.01).

• Risk of hepatotoxicity was not associated with HAART use or HCV positivity per se, in the absence of advanced fibrosis,

Conclusion

"In HIV infected patients, liver fibrosis is the one responsible for hepatotoxicity," the investigators concluded, adding that, "nearly one-third of patients with advanced fibrosis could develop hepatotoxicity."

08/24/07

Reference
N Marino, S Lo Caputo, C Blè, and others. Influence of liver fibrosis on highly active antiretroviral therapy-associated hepatotoxicity in HIV positive patients. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract MOPEB057.