AcNASH index to diagnose nonalcoholic steatohepatitis: a prospective derivation and global validation study. (November 2021)

• Record Type: Journal Article
• Authors: Wu, Xi-Xi; Zheng, Kenneth I.; Boursier, Jérôme; Chan, Wah-Kheong; Yilmaz, Yusuf; Romero-Gómez, Manuel; El Kassas, Mohamed; Targher, Giovanni; Byrne, Christopher D.; Huang, Zhi-Ming; Zheng, Ming-Hua
• Is Part Of: EClinicalMedicine. Volume 41(2021)
• Publication Date: 2021-11
• Subjects: Nonalcoholic steatohepatitis -- primary care -- screening -- metabolic dysfunction-associated fatty liver disease -- nonalcoholic fatty liver disease -- scoring system; NASH nonalcoholic steatohepatitis -- NAFLD nonalcoholic fatty liver disease -- AUROC area under receiver operating characteristics -- PPV positive predictive value -- NPV negative predictive value -- T2DM type 2 diabetes mellitus -- ALT alanine aminotransferase -- PERSONS Prospective Epidemic Research Specifically Of NASH -- e-GFR estimated glomerular filtration rate -- SCr serum creatinine -- HBV chronic viral hepatitis B -- HCV chronic viral hepatitis C -- BMI body mass index -- NAS NAFLD Activity Score -- CRN Clinical Research Network -- Se sensitivity -- Sp specificity -- GAA guanidine-acetic acid -- CKD-EPI Chronic Kidney Disease Epidemiology Collaboration -- AST aspartate aminotransferase; Medicine -- Research -- Periodicals; Medical policy -- Periodicals; Clinical Medicine; Health Policy; Public Health; Medical policy; Medicine -- Research; Periodical; Electronic journals; Periodicals; 613
• DOI: 10.1016/j.eclinm.2021.101145
• Languages: English
• ISSNs: 2589-5370

Abstract

Abstract: Background: There is an unmet need for non-invasive biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) in non-specialized settings. We aimed to develop and validate a non-invasive test for diagnosing NASH in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD). Methods: We developed a non-invasive test named the acNASH index that combines serum creatinine and aspartate aminotransferase levels in a derivation cohort of 390 Chinese NAFLD patients admitted to the hepatology center of the First Affiliated Hospital of Wenzhou Medical University (China) between December 2016 and September 2019 and subsequently validated in five external cohorts of different ethnicities of patients with biopsy-confirmed NAFLD (pooled n=1, 089). Findings: The performance of the acNASH index for identifying NASH (defined as NAFLD activity score ≥5 with score of ≥1 for each steatosis, lobular inflammation and ballooning) was good in the derivation cohort with an area under receiver operating characteristics (AUROC) of 0·818 (95%CI 0·777-0·860). A cutoff of acNASH index <4·15 gave a sensitivity (Se) of 91%, a specificity (Sp) of 48% and a negative predictive value (NPV) of 83% for ruling-out NASH, conversely, a cutoff of acNASH >7·73 gave a Sp of 91%, Se of 53% and a positive predictive value (PPV) of 85% for ruling-in NASH. In the pooled validation cohort (n=1, 089), the diagnostic performance of the index was also good with AUROC=0·805 (95%CI 0·780-0·830), NPV of 93% for ruling-out NASH and PPV of 73% for ruling-in NASH. Subgroup analyses showed similar performance in patients with diabetes or subjects with normal serum transaminase levels. Interpretation: The acNASH index shows promising utility as a simple non-invasive biomarker for diagnosing NASH among adults with biopsy-proven NAFLD of different ethnicities from different countries. Funding: The National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou.