Nonalcoholic Fatty Liver Disease Predicts Type 2 Diabetes in Patients With HIV

NAFLD with or without NASH was predictive of new-onset type 2 diabetes in patients with HIV infection, though further research is needed to assess long-term complications of NAFLD in this population.

Nonalcoholic fatty liver disease (NAFLD) with or without nonalcoholic steatohepatitis (NASH) increases the risk for new-onset type 2 diabetes among patients with HIV infection, according to results of a study published in Clinical Infectious Diseases.

Researchers conducted a longitudinal cohort study between 2013 and 2022 using data captured from adult patients with HIV infection and no history of excessive alcohol consumption or hepatitis coinfection. The researchers aimed to evaluate the connection between NAFLD (with or without NASH) and the risk for new-onset type 2 diabetes. They also assessed whether progression to NAFLD increases the risk for type 2 diabetes and whether tenofovir alafenamide (TAF) and integrase strand transfer inhibitor (INSTI) use is associated with increased risk for NAFLD or NASH. The primary outcome was new-onset type 2 diabetes; secondary outcomes included incident NASH and incident NAFLD.

A total of 847 patients were included in the study, of whom the median age was 45 (IQR, 38-51) years at baseline, and 43% were women. At enrollment, the median CD4+ count was 584 (IQR, 440-753) cells/mm3, the median BMI was 22.6 (IQR, 20.7-25.1) kg/m2, 28% of patients had NAFLD, 15% had NASH, and 6% were receiving TAF-based antiretroviral therapy (ART).

During a follow-up period of 2552 person-years, the overall incidence of type 2 diabetes was 10.9 (95% CI, 7.5-15.9) per 1000 person-years. The incidence of type 2 diabetes per 1000 person-years was higher among patients with (incidence rate [IR], 22.0; 95% CI, 13.6-36.3) vs without (IR, 6.5; 95% CI, 3.7-1.1) NAFLD at baseline (log-rank P <.001).

The presence of severe liver disease (NASH) amplifies the risk of new-onset DM for PWH with NAFLD.

The researchers performed a multivariable Cox regression analysis, adjusting for age, sex, BMI, smoking status, duration of ART use, dyslipidemia, hypertension, and family history of diabetes, among other variables. Results showed that the risk for type 2 diabetes was increased among patients with NAFLD with or without NASH compared with those without NAFLD at baseline (adjusted hazard ratio [aHR], 2.83; 95% CI, 1.26-6.36).

Further analysis showed that baseline NAFLD plus NASH with significant disease activity and liver fibrosis were significantly associated with new-onset type 2 diabetes (aHR, 3.12; 95% CI, 1.05-9.26). Although not significant, the risk for type 2 diabetes was also increased among patients with NASH alone.

Predictors of incident NASH included obesity, (aHR, 4.50; 95% CI, 1.95-10.36), receipt of ART for at least 10 years (aHR, 2.31; 95% CI, 1.12-5.11), and TAF use (aHR, 2.31; 95% CI, 1.12-5.11). Predictors of incident NAFLD included obesity, dyslipidemia, liver stiffness measurements of 7.5 kilopascals and above, and TAF use (aHR, 2.01; 95% CI, 1.02-4.02).

Study limitations include potential selection bias and the inability to control for unmeasured confounders such as genetic variants, lifestyle, and diet. These results may not be generalizable to other populations as all study patients were of Thai or Asian ancestry.

Based on these findings, “The presence of severe liver disease (NASH) amplifies the risk of new-onset DM [diabetes mellitus] for PWH [people with HIV] with NAFLD,” the researchers concluded.

Disclosures: Multiple study authors declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Infectious Disease Advisor


Han WM, Apornpong T, Su Lwin HM, et al. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis with liver fibrosis as predictors of new-onset diabetes mellitus in people living with HIV: a longitudinal cohort studyClin Infect Dis. Published online July 21, 2023. doi:10.1093/cid/ciad433