Dangerous Liaisons

NAFLD and Liver Fibrosis Increase Cardiovascular Risk in HIV

Adriana Cervo; Giada Sebastiani; Jovana Milic; Thomas Krahn; Sergio Mazzola; Salvatore Petta; Antonio Cascio; Giovanni Guaraldi; Giovanni Mazzola

Disclosures

HIV Medicine. 2022;23(8):911-921. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

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.[1] 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.[2] 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.[7] 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.[10] 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.[11] 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.[11]

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.

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