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Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard
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Clinical Infectious Diseases 15 June 2021

Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard.
Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%).
Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%.

The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.
Among persons living with human immunodeficiency virus (HIV; PLWH), liver disease is a leading cause of morbidity and mortality [1]. Historically, coinfection with viral hepatitis B and C were major contributors to liver disease among PLWH, but these risk factors are increasingly controlled with improved antiviral therapy for viral hepatitis. With increases in the long-term survival of PLWH and in the prevalence of metabolic syndrome, which affects approximately 25% of PLWH, HIV-associated nonalcoholic fatty liver disease (NAFLD) is emerging as a major cause of liver disease [2-4].
HIV-associated NAFLD occurs in the presence of metabolic risk factors and in the absence of viral hepatitis and pathologic alcohol use among PLWH. Although primary NAFLD and HIV-associated NAFLD have similar risk factors, multiple unique factors contribute to disease pathogenesis in PLWH including lipodystrophy [5], direct and indirect viral effects, and increased permeability of the gut epithelium [6]. The pathogenic role of antiretroviral therapy in HIV-associated NAFLD remains unclear and include older nucleoside reverse transcriptase inhibitors (NRTIs) causing mitochondrial toxicity, insulin resistance, and impaired fatty acid oxidation contributing to HIV-associated NAFLD [7]. Thus, multiple unique factors contribute to the pathogenesis of HIV-associated NAFLD. Several noninvasive imaging tests have been evaluated for the detection of liver fat including conventional ultrasound, computed tomography, and magnetic resonance spectroscopy but are limited by low sensitivity [8], ionizing radiation [9], and the requirement for technical expertise [10], respectively. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) is a technique that can be included in conventional MRI exams and is an accurate, reproducible biomarker for the detection of NAFLD and liver fat quantification that has similar accuracy to magnetic resonance spectroscopy (MRS) and is more widely available [11-19]. Although MRI-PDFF can be considered a useful reference standard for the quantification of liver fat, a low-cost point-of-care test would be ideal to screen a large at-risk population. Controlled attenuation parameter (CAP) is a novel ultrasound-based test to quantify liver fat during a liver stiffness (LS) measurement obtained by vibration-controlled transient elastography (VCTE) known as Fibroscan [20].
Although CAP is less accurate than MRI-PDFF [18], it does allow for a rapid, point-of-care, noninvasive assessment of elevated liver fat (MRI-PDFF ≥ 5%) with good sensitivity and specificity [21]. We hypothesized that the optimal CAP cutoff for HIV-associated NAFLD would be higher than 238 dB/m, which was not derived in patients with NAFLD and was utilized in many studies of HIV-associated NAFLD. The current study aims to evaluate the diagnostic accuracy of CAP for the diagnosis of HIV-associated NAFLD and to identify an optimal disease-specific threshold for detection of elevated liver fat using MRI-PDFF as the reference standard.
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