1. acNASH index to diagnose nonalcoholic steatohepatitis: a prospective derivation and global validation study
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Mohamed El Kassas, Manuel Romero-Gómez, Wah-Kheong Chan, Zhi-Ming Huang, Kenneth I. Zheng, Yusuf Yilmaz, Christopher D. Byrne, Ming-Hua Zheng, Xi-Xi Wu, Giovanni Targher, Jérôme Boursier, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Helwan University [Caire], University of Verona (UNIVR), National Natural Science Foundation of China, Public Health Department of Zhejiang Province, Wu, Xi-Xi, Zheng, Kenneth, I, Boursier, Jerome, Chan, Wah-Kheong, Yilmaz, Yusuf, Romero-Gomez, Manuel, El Kassas, Mohamed, Targher, Giovanni, Byrne, Christopher D., Huang, Zhi-Ming, and Zheng, Ming-Hua
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nonalcoholic fatty liver disease ,Metabolic dysfunction-associated fatty liver disease ,Medicine (General) ,Prospective Epidemic Research Specifically Of NASH ,ALT ,type 2 diabetes mellitus ,0302 clinical medicine ,aspartate aminotransferase ,HBV ,FIBROSIS ,Medicine ,GAA ,negative predictive value ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration ,AUROC ,NAS, NAFLD Activity Score ,URINARY CREATININE ,NASH ,ASSOCIATION ,General Medicine ,HBV, chronic viral hepatitis B ,Primary care ,3. Good health ,CRN ,NPV, negative predictive value ,HCV ,030211 gastroenterology & hepatology ,NASH, nonalcoholic steatohepatitis ,medicine.medical_specialty ,Renal function ,T2DM ,digestive system ,NPV ,03 medical and health sciences ,R5-920 ,NAFLD ,metabolic dysfunction-associated fatty liver disease ,metabolic dysfunction-associated fatty liver ,screening ,nutritional and metabolic diseases ,scoring system ,T2DM, type 2 diabetes mellitus ,medicine.disease ,sensitivity ,digestive system diseases ,Clinical Research Network ,NAS ,chronic viral hepatitis C ,HCV, chronic viral hepatitis C ,chronic viral hepatitis B ,NAFLD, nonalcoholic fatty liver disease ,area under receiver operating characteristics ,Body mass index ,Sp ,estimated glomerular filtration rate ,BMI, body mass index ,[SDV]Life Sciences [q-bio] ,CKD-EPI ,specificity ,AST, aspartate aminotransferase ,CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration ,GAA, guanidine-acetic acid ,Nonalcoholic fatty liver disease ,MUSCLE MASS ,SCr ,Se, sensitivity ,PERSONS, Prospective Epidemic Research Specifically Of NASH ,guanidine-acetic acid ,Screening ,Biomarker (medicine) ,Se ,Research Paper ,CRN, Clinical Research Network ,alanine aminotransferase ,Epidemiology  ,body mass index ,PPV ,NAFLD Activity Score ,serum creatinine ,e-GFR ,BMI ,primary care ,Diabetes mellitus ,Internal medicine ,ALT, alanine aminotransferase ,PERSONS ,SCr, serum creatinine ,Nonalcoholic steatohepatitis ,AST ,FATTY LIVER-DISEASE ,030304 developmental biology ,e-GFR, estimated glomerular filtration rate ,disease ,Receiver operating characteristic ,business.industry ,Hepatology ,Collaboration ,BIOMARKER PANEL ,PPV, positive predictive value ,MODEL ,Chronic Kidney Disease  ,AUROC, area under receiver operating characteristics ,positive predictive value ,Sp, specificity ,Steatosis ,business - 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 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., 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.
- Published
- 2021
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