Background: Patients with HIV infection and non-alcoholic fatty liver disease (NAFLD) are at increased risk for progression to advanced fibrosis. We aimed to validate the accuracy of serological biomarkers to detect NAFLD and advanced fibrosis in HIV mono-infected patients.
Methods: From Jun-2015 to Jan-2018, HIV-infected patients (n=547) were prospectively enrolled in the PROSPEC-HIV study [NCT02542020]. At entry, a clinical evaluation, laboratory testing, and liver stiffness measurement (LSM) / Controlled Attenuation Parameter (CAP) using transient elastography (Fibroscan) were performed. Patients with viral hepatitis co-infection (n=17), abusive alcohol intake [AUDIT>8 (n=54)] or unreliable Fibroscan (n=39) results were excluded. NAFLD was defined by CAP≥248 dB/m and advanced fibrosis by LSM≥8.7 kPa with M or ≥7.2 kPa with XL probes, respectively. Serological biomarkers for steatosis [Steato-ELSA, Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), NAFLD Liver Fat Score (NAFLD-LFS)] and fibrosis [FIB-4, APRI and NAFLD Fibrosis Score (NFS)] were calculated. The area under the ROC curves (AUROC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood-ratio (LR) were assessed.
Results: 437 patients [57% female, median age=44 (IQR 35-52) years, BMI=26.1 (23.4-29.3) Kg/m², ALT=30 (23-43)U/L, CD4=660 (427-901) cells/mm³] were included. The prevalence [95%CI] of NAFLD and advanced fibrosis were 38% [34-43] and 11% [8-14], respectively. The AUROCs [95%CI] for diagnosis of NAFLD were 0.854 [0.818-0.889], 0.840 [0.804-0.877], 0.805 [0.762-0.847] and 0.793 [0.750-0.836] for Steato-ELSA; FLI; HSI and NAFLD-LFS [p< 0.001], respectively. The AUROCs [95%CI] for diagnosis of advanced fibrosis were 0.736 [0.659-0.814], 0.700 [0.614-0.7851] and 0.795 [0.726-0.864] for FIB-4, APRI and NFS [p=0.077], respectively. The table shows sensitivities, specificities, PPV, NPV and LR.
Conclusions: Serological biomarkers accurately predicts steatosis; use in patients with fibrosis demonstrated high specificity and NPV. Integration of these tests should be encouraged as part of routine HIV management for the detection of NAFLD and to exclude advanced liver fibrosis.