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LIVER INFLAMMATION IS COMMON AND LINKED TO METABOLIC DERANGEMENTS IN TREATED HIV
Kara W. Chew1, Katherine Tassiopoulos2, Frank J. Palella3, Kunling Wu2, Susanna Naggie4, Netanya S. Utay5, Edgar T. Overton6, Mark Sulkowski7
1University of California Los Angeles, Los Angeles, CA, USA,2Harvard University, Boston, MA, USA,3Northwestern University, Chicago, IL, USA,4Duke University, Durham, NC, USA,5University of Texas at Houston, Houston, TX, USA,6University of Alabama at Birmingham, Birmingham, AL, USA,7Johns Hopkins University, Baltimore, MD, USA
Abnormal serum liver enzymes in people with HIV (PWH) are common and often unexplained. We sought to identify the prevalence of and underlying reasons for aspartate and alanine aminotransferase (AST and ALT) elevation in a well-characterized cohort of adults with treated HIV without hepatitis C or B virus (HCV or HBV) infection or heavy alcohol use.
Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort who did not report heavy alcohol use, were negative for anti-HCV and hepatitis B surface antigen, and with at least 2 AST and ALT measures between 11/2013–2/2018 were included. Clinical and demographic characteristics, including the Hepatic Steatosis Index (HSI = 8x(ALT/AST)+BMI (+2 female, +2 diabetes)), FIB-4 score and metabolic syndrome (MetS) were compared between persons with and without ≥1 elevated AST or ALT (defined as AST >36 and ALT >30 U/L for men and AST >30 and ALT >19 U/L for women), using chi-square and Wilcoxon tests and multiple logistic regression models. Covariates with p<0.10 in univariate analysis were included in the multivariable models.
Of 1035 participants, 662 met criteria for inclusion; 456 (69%) had ≥ 1 and 236 (36%) ≥ 2 elevated AST/ALT during a median of 4.0 years of follow-up. Median age at entry was 51 years; 138 (21%) female; 184 (28%) black and 122 (18%) Hispanic; median entry and nadir CD4 cell counts/mm3 (CD4) 621 and 195, respectively; and 627 (95%) had plasma HIV RNA <200 copies/mL at entry. In univariate analysis, the elevated liver enzyme group was younger, had a higher proportion of Hispanic and female participants, higher entry CD4 without differences in nadir CD4, higher HSI score, and a higher proportion with MetS and HSI ≥ 36 (p<0.05 for all). There were no differences in the proportions with HIV RNA suppression or antiretroviral use (current or previous); FIB-4 score was similar in each group. The Table summarizes the results from multiple logistic regression models.
After exclusion of HCV, HBV and alcohol, liver enzyme elevation was remarkably common in this cohort and independently associated with metabolic disease, presence of hepatic steatosis by HSI, Hispanic ethnicity, and lower CD4 at entry. These findings suggest that NAFLD may be a common cause of liver inflammation in PWH receiving suppressive antiretroviral therapy (ART). Further research is needed to understand the contribution of NAFLD and other mechanisms of liver injury in PWH on suppressive ART.