Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis With Liver Fibrosis as Predictors of New-Onset Diabetes Mellitus in People With HIV: A Longitudinal Cohort Study

• Published in: Clinical infectious diseases 2023-12, Vol.77 (12), p.1687-1695
• Main Authors: Han, Win Min, Apornpong, Tanakorn, Lwin, Hay Mar Su, Thammapiwan, Siwat, Boonrungsirisap, Jedsadakorn, Gatechompol, Sivaporn, Ubolyam, Sasiwimol, Tangkijvanich, Pisit, Kerr, Stephen J, Avihingsanon, Anchalee
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Cohort Studies; Diabetes Mellitus - epidemiology; Female; HIV; HIV Infections - complications; HIV Infections - epidemiology; HIV Infections - pathology; Humans; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - epidemiology; Longitudinal Studies; Male; Middle Aged; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - epidemiology; Prospective Studies
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciad433

Abstract Background We investigated the association between nonalcoholic fatty liver disease (NAFLD) plus or minus a concurrent diagnosis of nonalcoholic steatohepatitis (NASH) and incident diabetes mellitus (DM) and the risk factors associated with NAFLD or NASH development. Methods In this prospective study, we analyzed people with human immunodeficiency virus (HIV; PWH) aged ≥18 years without excessive alcohol consumption or hepatitis coinfections. NAFLD was defined as controlled attenuation parameter ≥248 dB/m, whereas NASH with significant disease activity and liver fibrosis was defined as a FibroScan-AST score ≥0.67. Cox proportional hazard regression was used to investigate the association between NAFLD with or without NASH and new-onset DM. Results Of 847 PWH, the median age at baseline was 45 years (interquartile range, 38–51; 43% female). Baseline NAFLD was associated with 2.8-fold higher risk of new-onset DM after adjusting for age, sex, family history of DM, antiretroviral therapy duration, smoking, statin use, stavudine/didanosine/zidovudine exposure, time-updated body mass index, hypertension, and dyslipidemia. Combined NAFLD and NASH at baseline had 3.1-fold higher new-onset DM risk. In separate analyses, baseline DM did not predict progression to NAFLD or NASH, but tenofovir alafenamide use was associated with an increased risk of NAFLD (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.02–4.02) or NASH development (2.31; 95% CI, 1.12–5.11). Conclusions NAFLD alone or combined with NASH strongly predicts new-onset DM. This highlights the need for systematic risk assessments and management of NAFLD/NASH, as it may contribute to metabolic complications such as DM and subsequent cardiovascular diseases in PWH. People with human immunodeficiency virus with nonalcoholic fatty liver disease at baseline or during follow-up had a higher new-onset diabetes mellitus risk. Tenofovir alafenamide was linked to an increased risk of NAFLD and nonalcoholic steatohepatitis with significant activity and fibrosis. Graphical Abstract Graphical Abstract