Chronic alanine aminotransferase elevation in people with HIV: Time trends over 22 years and genetic predisposition
Within the SHCS, Simon NR et al investigated time trends in chronic alanine aminotransferase (cALT) elevation, defined as elevated ALT levels at two consecutive six-monthly visits, and associated clinical and HIV-related risk factors among people with HIV. They included almost 9000 participants without viral hepatitis coinfection between 2002 and 2023, contributing over 200,000 ALT measurements. In addition, they performed a matched case–control analysis including 950 cALT cases and 950 controls to investigate clinical risk factors and genetic predisposition using a polygenic risk score (PGS).
Overall, 8414 cALT events occurred. The annual prevalence of cALT increased from 7.5% in 2002 to 10.1% in 2005, followed by a significant decline to 5.3% in 2018, remaining stable thereafter (5.5% in 2023). Interestingly, this decline occurred despite increasing body mass index over the study period. In multivariable analyses, obesity (odds ratio [OR] 2.84), hypertension (OR 1.82), dyslipidemia (OR 1.39), history of CDC stage C illness (OR 1.38), and 6–12 months of exposure to non-nucleoside reverse transcriptase inhibitors (OR 2.09) or tenofovir disoproxil fumarate (OR 1.99) were associated with cALT. Participants in the highest PGS quintile had more than fourfold higher odds of cALT compared with those in the lowest quintile (OR 4.44). Adding the PGS improved the predictive performance of the multivariable model (area under the curve 0.740 to 0.792).
In conclusion, the authors found an almost 50% decrease in cALT prevalence since 2005, potentially related to changes in antiretroviral drugs prescribed. Genetic predisposition emerged as a strong independent risk factor for cALT, exceeding the associations observed for established clinical risk factors. Although the clinical utility of genetic testing remains unproven, these findings suggest a potential future role for genetic risk assessment in individualized HIV care.