Background Nonalcoholic fatty liver disease (NAFLD) is a major non–AIDS-defining condition for persons living with HIV (PLWHIV). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PLWHIV. Methods Cross-sectional study of PLWHIV on stable ART with persistently elevated transaminases and no known liver disease. The AUROC was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (including CAP), and noninvasive markers of steatosis (TyG, HSI, FLI) and fibrosis (FIB-4, APRI, NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F≥3). The AUROC for steatosis was: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49– 1). For liver fibrosis ≥ F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC, 0.99 (0.97–1, P < 0.001) and 0.92 (0.77–1, P < 0.001). Conclusions Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.
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