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Risk factors of metabolic dysfunction-associated fatty liver disease in people with HIV receiving antiretroviral therapy
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Yuan, Ruia,b,*; Yan, Yajuna,c,*; Deng, Lipinga,c,*; Li, Feid,*; Chen, Qianhuia,c; Gui, Xiena,c; Xiong, Yonga,c; Yang, Rongronga,c
AIDS May 2026
Widespread use of ART has led to a considerable reduction in the all-cause death rate among PWH. The higher life expectancy of PWH is also expected to increase the risk of MAFLD and other aging-related noncommunicable diseases [10]. Among this group, liver-related complications remain the leading cause of death. With an estimated global frequency of 25% [11], MAFLD is becoming a major public health concern. It worsens more quickly and more severely in PWH
These findings suggest that extended ART duration is associated with a marked and progressive increase in MAFLD risk among PWH. Particularly noteworthy was the development of obesity (BMI ≥ 24 kg/m2) after 1 year of treatment, which was associated with a dramatic increase in MAFLD risk (OR = 19.84), weight gain exceeding 5% within 1 year also demonstrated an elevated risk trend. A strong association was observed between weight gain magnitude and MAFLD risk, with individuals gaining ≥5% weight having a significantly elevated risk compared to those gaining <5% (P < 0.05). The MAFLD detection rate surpassed 85% in patients with 5% or more weight gain after ART initiation for 3 years, which was markedly higher than the 65.8% seen in the group with less than 5% weight gain.
The reported prevalence of MAFLD in PWH ranges from 28% to 48% [14-16]. In our cohort, the prevalence was 28.7% at baseline and rose to 57.4% after three years of ART, a trend that aligns with the global annual increase of about 1% in steatosis [17]. Consistent with established risk factors in both HIV and non-HIV populations [18,19], we found MAFLD to be associated with TG >1.7 mmol/l, type 2 diabetes, weight gain, and BMI >24 kg/m2 after adjusting for confounders. Beyond these factors, we newly identified AZT/3TC-containing therapy as a potential protective factor against MAFLD. First-generation NRTIs (zalcitabine (ddC), ddI, d4T, and AZT) exhibit significant mitochondrial toxicity, increasing lactate production and abnormal lipid oxidation in the liver, leading to steatosis and other lipid disorders [26].
The frequency of overweight and obesity among PWH is increasing, with the initiation of ART frequently resulting in weight increase [31]. One theory for the weight increase linked to ART is the phenomenon known as “return to health,” which happens once an individual's weight rebounds to its preillness level, particularly in cases of advanced HIV disease [32]. Grant et al.[33] related the phenomenon to early weight gain following initiating ART, demonstrating that PWH, especially those with lower baseline CD4+ T cell count and BMI, showed substantial rises in lean body mass and fat mass during the first 96 weeks. These improvements represent physiological benefits from immunological reconstitution and reduced inflammation [34]. However, long-term excessive weight gain considerably increases the risk of noncommunicable diseases as MAFLD [35,36].
Objective:
This study aimed to identify risk factors associated with the onset and progression of metabolic dysfunction-associated fatty liver disease (MAFLD) in people with human immunodeficiency virus (PWH).
Methods:
Clinical and laboratory data were retrospective collected at 6 months, 1, 1.5, 2, and 3 years after ART initiation. Multivariable logistic regression was employed to identify MAFLD risk factors and evaluate ART's influence.
Results:
Among the 740 participants (95% male, mean age 36.58 ± 13.93 years), with an average ART duration of 3.33 ± 4.56 years. Laboratory data at 6 months showed a CD4+ cell count of (356.95 ± 98.76) cells/mm3, body mass index (BMI) of (22.87 ± 7.47) kg/m2, triglycerides (TG) of (1.53 ± 0.98) mmol/l and low-density lipoprotein cholesterol (LDL-c) of (2.45 ± 0.71) mmol/l.
MAFLD detection rates by hepatic steatosis index (HSI) and Zhejiang University indices (ZJU) increased with longer ART duration.
Patients with >10% weight gain showed a notable rise from 48.80% at baseline to 87% after 3 years of ART.
Independent risk factors for MAFLD included female, type 2 diabetes mellitus (T2DM) prior MAFLD, baseline BMI >24 kg/m2 and TG ≥1.7 mmol/l, weight gain of 5-10% or >10% within 1 year, BMI ≥24 kg/m2 and TG ≥1.7 mmol/l at year 1. Protective factors included age >65 years, AZT and 3TC-based therapies.
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