Influence of Antiretroviral Drugs on Liver Fibrosis Progression in HIV-HCV Coinfected Patients

By Liz Highleyman

As effective antiretroviral therapy has dramatically lowered the rate of mortality due to AIDS, liver disease has become a leading cause of death among HIV positive individuals. The highest rates of liver-related death are seen in people with pre-existing chronic liver disease such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, but certain antiretroviral drugs may cause or exacerbate liver damage.

Several studies have shown that HIV-HCV coinfected patients experience more rapid liver disease progression compared to those with HCV alone, although this appears less likely individuals with well-controlled HIV and high CD4 cell counts.

As reported at the 42nd Annual Meeting of the European Association for the Study of the Liver last month in Barcelona, Spanish researchers conducted a study to assess the impact of antiretroviral therapy on fibrosis progression in coinfected patients. The analysis included all consecutive HIV positive patients with chronic HCV infection (HCV RNA positive) followed at Hospital Carlos III in Madrid. Advanced liver fibrosis was defined as liver stiffness > 9.5 Kpa using the transient elastometry technique (FibroScan).

The researchers conducted a further analysis of coinfected patients receiving antiretroviral therapy, accounting for 3291 total person-years of exposure. Distribution of antiretroviral therapy exposure was as follows:

• 3.5% were HAART-naive;
• 34.7% had taken nevirapine (Viramune);
• 48.7% and taken efavirenz (Sustiva, Stocrin);
• 74.1% had taken protease inhibitors (PIs).

Results

• A total of 489 HIV-HCV coinfected patients were identified, of whom 37% had advanced liver fibrosis.

• In a univariate analysis, the follow factors were significantly associated with advanced fibrosis (comparison between patients with and without severe fibrosis):

o older age (mean 44 vs 42 years);
o male sex (76% vs 67%);
o current or past heavy alcohol consumption (55% vs 34%);
o higher mean CD4 cell count (486 vs 553 cells/mm3)
o higher peak HCV RNA level (6.4 vs 6 log IU/mL);
o higher ALT level (88 vs 64 IU/L);
o higher blood glucose (102 vs 98 mg/dL);
o higher triglycerides (167 vs 148 mg/dL).

• There was a significant association between liver fibrosis and duration of PI exposure (P = 0.01).

• This association was even more pronounced for ritonavir-boosted PIs (P < 0.001).

• However, no correlation with fibrosis was observed for any nucleoside reverse transcriptase inhibitors (NRTIs) or for the NNRTIs nevirapine or efavirenz.

• Mean biochemical parameters while using regimens containing NNRTIs vs boosted PIs were as follows:

o ALT: 85.6 vs 81.0 IU/L;
o blood glucose: 99.6 vs 99.9 mg/dL;
o triglycerides: 162 vs 179.

• In a multivariate analysis, factors independently associated with advanced liver fibrosis were:

o heavy alcohol use (OR 2.1);
o low CD4 cell count (OR 0.8 per 100 cells/mm3);
o elevated ALT (OR 1.2 per 10 IU/L);
o elevated blood glucose (OR 1.5 per 10 mg/dL).

Conclusion

"The influence of HAART on the progression of liver fibrosis in HIV-HCV coinfected patients may be a 'double-edged sword'," the investigators concluded. "While liver fibrosis progression could be delayed by enhancing CD4 counts, causing episodes of ALT elevations and higher glucose and triglyceride levels HAART might accelerate liver damage."

05/04/07

Reference
P Barreiro, L Martin-Carbonero, F Blanco, and others. Influence of Antiretrovirals in the Progression of Liver Fibrosis in HCV/HIV Coinfected Patients: Effect of Hepatoxicity and Metabolic Abnormalities. 42nd Annual Meeting of the European Association for the Study of the Liver. April 11-15, 2007. Barcelona, Spain.