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Prolonged ART and Risk for Chronic Elevation of Alanine Aminotransferase in HIV-infected Persons without HBV or HCV Co-infections
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In multivariable models, prolonged ART, NRTI exposure, PI exposure, increased body mass index, and high alcohol use were associated with chronic ALT elevation. Long-term follow-up is needed to assess whether chronic ALT elevation will result in increased morbidity or mortality.
Reported by Jules Levin CROI 2009 Montreal Feb 8-12
Helen Kovari*1, B Ledergerber1, M Battegay2, H Furrer3, B Hirschel4, M Cavassini5, P Vernazza6, E Bernasconi7, N Mueller1, R Weber1, and the Swiss HIV Cohort Study
1Univ Hosp Zurich, Switzerland; 2Univ Hosp Basel, Switzerland; 3Univ Hosp Bern, Switzerland; 4Univ Hosp Geneva, Switzerland; 5Univ Hosp Lausanne, Switzerland; 6Cantonal Hosp, St Gallen, Switzerland; and 7Regional Hosp, Lugano, Switzerland
Background: Chronic liver disease in HIV-infected patients is mostly due to hepatitis virus co-infections or alcohol use. ART-related liver toxicity is recognized but rare.
Methods: We studied the incidence of and risk factors for new and chronic elevation of alanine aminotransferase (ALT) in participants of the Swiss HIV Cohort Study, seen between 2002 and 2006, without hepatitis B or C virus (HBV/HCV) infections, with ≥3 semi-annual visits, and normal baseline ALT.. Chronic ALT elevation was defined as ALT >50 (males)/>35 U/L (females) at ≥2 consecutive semi-annual visits. Poisson regression analysis was used.
Results: We followed 2445 participants for 9795 person-years (median age 39 years; 66.6% male; 83.7% Caucasian; HIV transmission 54% heterosexual, 40% homosexual, 1% injection drug use [IDU]; median CD4 cells 436/μL; 31.5% ART-naive; 57.9% on ART, 10.6% interrupted ART); 365 (14.9%) newly developed chronic ALT elevation (incidence 3.73 [95%CI 3.36 to 4.13] per 100 person-years).Univariable analyses showed associations between chronic elevated ALT and increased body mass index, increased waist circumference, fat accumulation, fat loss, hypertension, plasma cholesterol, triglyceride, and time-updated cumulative exposure to NRTI, NNRTI, and PI. Multivariable models, considering that many of these variables are collinear or on the same causal pathway, confirmed the association between chronic ALT elevation and increased body mass index (IRR per kg/m2 1.06 [95%CI 1.03 to 1.09], p <0.001), ART per year of exposure (IRR 1.04 [1..01 to 1.07], p = 0.004), NRTI per year exposure (1.04 [1..02 to 1.08], p = 0.003), PI per year exposure (1.04 [1.01 to 1.08], p = 0.013), but not with NNRTI exposure (IRR 1.03 [0.98 to 1.08]). Median alcohol use among non-abstinent patients was 10 g/day in persons with and without ALT elevation. Compared with no alcohol use (30% of patients), light (women <20 g/d, men <40 g/d; 57%) and moderate (20 to 40/40 to 60 g/d; 9%) alcohol use was not, but high use (>40/>60 g/d; 4% of patients) was associated with chronic ALT elevation (IRR 1.83 [1.16 to 2.87], p = 0.009).. Treatment outcome and changes as well as mortality did not differ between patients with and without ALT elevation.
Conclusions: The incidence of chronic ALT elevation was 3.7/100 person-years in patients without hepatitis virus co-infections. In multivariable models, prolonged ART, NRTI exposure, PI exposure, increased body mass index, and high alcohol use were associated with chronic ALT elevation. Long-term follow-up is needed to assess whether chronic ALT elevation will result in increased morbidity or mortality.
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