Mohammed Eslam1, Grace Lai-Hung Wong2,3, Ahmed M Hashem4, Henry Lik-Yuen Chan2,3, Mette Juul Nielsen5, Diana Julie Leeming5, Anthony Wing-Hung Chan6, Yu Chen7, Kevin L Duffin7, Morten Karsdal5, Jörn M Schattenberg8, Jacob George1, Vincent Wai-Sun Wong2,3. 1. Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Westmead, and University of Sydney, Sydney, Australia. 2. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. 3. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. 4. Department of Systems and Biomedical Engineering, Faculty of Engineering, Minia University, Minia, Egypt. 5. Nordic Bioscience Biomarkers and Research A/S, Herlev, Denmark. 6. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China. 7. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA. 8. Department of Medicine, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.
Abstract
INTRODUCTION: Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking. METHODS: Three independent cohorts, 2 with both liver biopsy and liver stiffness measurements (LSMs, n = 254 and 65) and a population sample (n = 713), were studied. The performance of a recently developed noninvasive algorithm (ADAPT [age, diabetes, PRO-C3 and platelets panel]) as well as aspartate aminotransferase-to-platelet ratio index, fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and LSM was used to stage patients for significant (≥F2) and advanced (≥F3) fibrosis. RESULTS: In the hospital-based cohorts, the N-terminal propeptide of type 3 collagen (Pro-C3) increased with fibrosis stage (P < 0.0001) and independently associated with advanced fibrosis (odds ratio = 1.091, 95% confidence interval [CI]: 1.053-1.113, P = 0.0001). ADAPT showed areas under the receiver operating characteristics curve of 0.831 (95% CI: 0.779-0.875) in the derivation and 0.879 (95% CI: 0.774-0.946) in the validation cohort for advanced fibrosis. This was superior to the existing fibrosis scores, aspartate aminotransferase-to-platelet ratio index, fibrosis-4, BARD (BMI, aspartate aminotransferase to alanine aminotransferase ratio [AAR], diabetes), and nonalcoholic fatty liver disease fibrosis score in most comparisons and comparable with LSM. Serial use of ADAPT and LSM had diagnostic accuracy of 92.5%, with 98% and 100% negative predictive value in the derivation and validation cohorts, respectively. In the population cohort, PRO-C3 associated with advanced fibrosis (P = 0.04), while ADAPT had a negative predictive value of 98% for excluding advanced fibrosis. DISCUSSION: PRO-C3 and ADAPT reliably exclude advanced fibrosis in low-risk populations. The serial combination of ADAPT with LSM has high diagnostic accuracy with a low requirement for liver biopsy. The proposed algorithm would help stratify those who need biopsies and narrow down those patients who would need to be referred to specialty clinics.
INTRODUCTION: Metabolic-associated fatty liver disease is common, with fibrosis the major determinant of adverse outcomes. Population-based screening tools with high diagnostic accuracy for the staging of fibrosis are lacking. METHODS: Three independent cohorts, 2 with both liver biopsy and liver stiffness measurements (LSMs, n = 254 and 65) and a population sample (n = 713), were studied. The performance of a recently developed noninvasive algorithm (ADAPT [age, diabetes, PRO-C3 and platelets panel]) as well as aspartate aminotransferase-to-platelet ratio index, fibrosis-4, nonalcoholic fatty liver diseasefibrosis score, and LSM was used to stage patients for significant (≥F2) and advanced (≥F3) fibrosis. RESULTS: In the hospital-based cohorts, the N-terminal propeptide of type 3 collagen (Pro-C3) increased with fibrosis stage (P < 0.0001) and independently associated with advanced fibrosis (odds ratio = 1.091, 95% confidence interval [CI]: 1.053-1.113, P = 0.0001). ADAPT showed areas under the receiver operating characteristics curve of 0.831 (95% CI: 0.779-0.875) in the derivation and 0.879 (95% CI: 0.774-0.946) in the validation cohort for advanced fibrosis. This was superior to the existing fibrosis scores, aspartate aminotransferase-to-platelet ratio index, fibrosis-4, BARD (BMI, aspartate aminotransferase to alanine aminotransferase ratio [AAR], diabetes), and nonalcoholic fatty liver diseasefibrosis score in most comparisons and comparable with LSM. Serial use of ADAPT and LSM had diagnostic accuracy of 92.5%, with 98% and 100% negative predictive value in the derivation and validation cohorts, respectively. In the population cohort, PRO-C3 associated with advanced fibrosis (P = 0.04), while ADAPT had a negative predictive value of 98% for excluding advanced fibrosis. DISCUSSION: PRO-C3 and ADAPT reliably exclude advanced fibrosis in low-risk populations. The serial combination of ADAPT with LSM has high diagnostic accuracy with a low requirement for liver biopsy. The proposed algorithm would help stratify those who need biopsies and narrow down those patients who would need to be referred to specialty clinics.
Authors: Elisabeth Erhardtsen; Daniel G K Rasmussen; Peder Frederiksen; Diana Julie Leeming; Diane Shevell; Lise Lotte Gluud; Morten Asser Karsdal; Guruprasad P Aithal; Jörn M Schattenberg Journal: JHEP Rep Date: 2021-07-10
Authors: Yasser Fouad; Melissa Palmer; Minjun Chen; Arie Regev; Rajarshi Banerjee; Rob Myers; Robert Riccio; Richard Torstenson; Ramy Younes; Puneet S Arora; Henrik Landgren; Morten A Karsdal; Martin Blake; David A Shapiro; Hans-Juergen Gruss; Muhammad Y Sheikh; Dina Attia; Steven Bollipo; Alastair D Smith; Bradley Freilich; Robert G Gish; Detlef Schuppan Journal: J Clin Transl Hepatol Date: 2021-10-22
Authors: Anne Linde Mak; Jenny Lee; Anne-Marieke van Dijk; Yasaman Vali; Guruprasad P Aithal; Jörn M Schattenberg; Quentin M Anstee; M Julia Brosnan; Mohammad Hadi Zafarmand; Dewkoemar Ramsoekh; Stephen A Harrison; Max Nieuwdorp; Patrick M Bossuyt; Adriaan G Holleboom Journal: Biomedicines Date: 2021-12-15