Is 1 Alanine Transaminase >200 IU Enough to Define an Alanine Transaminase Flare in HIV-Infected Populations? A New Definition Derived From a Large Cohort Study


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Abstract

Objectives:Recent studies have suggested that highly active antiretroviral therapy may lead to rises in alanine transaminase (ALT) among HIV-infected patients. However, the definition of an ALT flare is arbitrary and the extent to which such increases represent normal fluctuations has not been explored.Methods:Using data from untreated, hepatitis B virus/hepatitis C virus-negative, HIV-infected patients, we derived a definition for an ALT flare by exploring a series of ALT thresholds (from 100 to 200 IU/L). The resulting definition (2 consecutive ALTs > 200 measured >2 weeks apart) was applied to all patients in the UK Collaborative HIV Cohort (CHIC) Study, and Poisson regression was used to identify factors associated with ALT flares.Results:Five hundred and twenty six of 12,206 eligible patients (4.3%) had ≥1 ALT flare, resulting in a total of 615 episodes of ALT flares. The overall rate of an ALT flare was 1.19 (95% confidence interval: 1.10 to 1.28) per 100 person-years. Higher risk of ALT flare was associated with lower CD4 counts, detectable viral loads, being under follow-up in earlier calendar years, prior clinical AIDS, receipt of nevirapine either with didanosine/stavudine or without didanosine/stavudine, receipt of ritonavir, detectable anti-hepatitis C virus, and detectable hepatitis B surface antigen.Conclusions:Associations between known risk factors may be under/over estimated if using single values, that is, 1 ALT > 200, to define ALT flares. We recommend studies to use a more stringent measure and suggest our derived definition of an ALT flare.

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