Abstract and Introduction
Objectives: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. We aimed to assess the impact of NAFLD and liver fibrosis on intermediate-high cardiovascular risk in people living with HIV.
Methods: We included people living with HIV from three cohorts. NAFLD and significant liver fibrosis were defined using transient elastography: controlled attenuation parameter ≥288 dB/m and liver stiffness measurement ≥7.1 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator in patients aged between 40 and 75 years and categorised as low if <5%, borderline if 5%–7.4%, intermediate if 7.5%–19.9% and high if ≥20% or with the presence of a previous cardiovascular event. Patients with hepatitis B and/or hepatitis C virus co-infection, alcohol abuse and unreliable transient elastography measurements were excluded. Predictors of intermediate-high cardiovascular risk were investigated in multivariable analysis by logistic regression and also by stratifying according to body mass index (BMI; cut-offs of 25 and 30 kg/m2) and age (cut-off of 60 years).
Results: Of 941 patients with HIV alone included, 423 (45%), 128 (13.6%), 260 (27.6%) and 130 (13.8%) were categorised as at low, borderline, intermediate and high ASCVD risk, respectively. Predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.11; 95% confidence interval [CI] 1.40–3.18; p < 0.001), liver fibrosis (aOR 1.64; 95% CI 1.03–2.59; p = 0.034), duration of HIV (aOR 1.04; 95% CI 1.02–1.06; p < 0.001), and previous exposure to thymidine analogues and/or didanosine (aOR 1.54; 95% CI 1.09–2.18; p = 0.014). NAFLD was also associated with higher cardiovascular risk in normoweight patients (aOR 2.97; 95% CI 1.43–6.16; p = 0.003), in those with BMI <30 kg/m2 (aOR 2.30; 95% CI 1.46–3.61; p < 0.001) and in those aged <60 years (aOR 2.19; 95% CI 1.36–3.54; p = 0.001).
Conclusion: Assessment of cardiovascular disease should be targeted in people living with HIV with NAFLD and/or significant liver fibrosis, even if they are normoweight and young.
With HIV becoming a long-term chronic disease, liver and cardiovascular diseases are now the leading causes of comorbidity and non-AIDS-related deaths in people living with HIV in Western countries. Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver pathologies, from simple steatosis to non-alcoholic steatohepatitis, fibrosis and cirrhosis, emerging as a clinically significant cause of chronic liver disease in people living with HIV. The prevalence of NAFLD ranges from 13% to 65% in people living with HIV,[2–4] such individuals are at higher risk for NAFLD, and the risk of developing liver fibrosis is two times higher than in those without HIV.[5,6] The global burden of HIV-associated cardiovascular disease (CVD) has tripled over the past two decades and accounts for 2.6 million disability-adjusted life-years per year. CVD occurs earlier and more commonly in people living with HIV, who have an estimated 1.5- to 2-fold greater risk of various cardiovascular manifestations than those without HIV.[7,8] The excess prevalence of NAFLD and CVD in people with HIV compared with those without is driven by the complex interplay among traditional risk factors and HIV-specific features (i.e. chronic inflammation, immune activation in the setting of suppressed HIV disease, toxicities related to antiretroviral therapies [ART] and mitochondrial stress).[4,9] An increasingly wide body of literature evidences a strong interrelation between NAFLD and CVD in the general population. Some data suggest that NAFLD, and especially NAFLD with severe liver fibrosis, may be actively involved in the pathogenesis of CVD, independent of features of metabolic syndrome. The correlation between NAFLD and CVD might be even more peculiar in people with HIV because of HIV-specific factors that may interfere in this complex interplay.
The aim of this study was to evaluate the association between NAFLD and significant liver fibrosis with intermediate-high cardiovascular risk in individuals living with HIV.
HIV Medicine. 2022;23(8):911-921. © 2022 Blackwell Publishing