Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study

Abstract

Introduction:Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries(LMICs),there is limited information about the burden of metabolic disorders on liver disease in PLHIV. Methods:We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 fromtheIeDEA-Sentinel Research Network,a prospective cohort enrolling PLHIV≥40 years on antiretroviral treatment (ART)for≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated withliver fibrosis (LSM≥7.1 kPa) and steatosis (CAP≥248 dB/m). Population attributable fraction (PAF) of each variable associ-ated with significant liver fibrosis was estimated using Levin’s formula. Results:Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45−56] years) were included. The preva-lence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia.The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1−8.4) and 28.4% (95% CI26.5−30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10−2.40), overweight/obesity(OR=2.50, 95% CI 1.69−3.75), T2DM (OR 2.26, 95% CI 1.46−3.47) and prolonged exposure to didanosine (OR 3.13, 95%CI1.46−6.49)wereassociatedwithliverfibrosis.Overweight/obesityandT2DMaccountedfor42%and11%ofthePAFforliver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis includedoverweight/obesity(OR4.25,95%CI3.29−5.51),T2DM(OR2.06,95%CI1.47−2.88),prolongedexposuretostavudine(OR1.69,95%CI1.27−2.26)anddyslipidaemia(OR1.68,95%CI1.31−2.16).Conclusions:Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings