• Christian Labenz, Gerrit Toenges, Ming-Hua Zheng, Dora Ding, Robert P Myers, Peter R Galle, Angelo Armandi, Javier Ampuero, GómezManuel RomeroMRDigestive Disease Department, Virgen del Rocio University Hospital, Sevilla, Spain. Electronic address: mromerogomez@us.es., Elisabetta Bugianesi, Quentin M Anstee, and Jörn M Schattenberg.
• Department of Internal Medicine I, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Metabolic Liver Research Program, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. Electronic address: christian.labenz@unimedizin-mainz.de.
• Eur. J. Intern. Med. 2022 Apr 1; 98: 53-60.

Separation of bridging fibrosis from cirrhosis in non-alcoholic fatty liver disease (NAFLD) is critical to guide management. Therefore, it was the aim of this study to develop an easy-to-perform score distinguishing F3 and F4 fibrosis in NAFLD. A derivation cohort comprising 251 NAFLD patients with F3 or F4 was used to develop the NAFLD Cirrhosis Score (NCS). The NCS was validated in three independent cohorts with liver histology comprising 1666 participants from the STELLAR trials, 47 patients from China and 2058 patients from the European NAFLD Registry. A model including INR, gGT, ALT, platelets and age discriminated best between patients with bridging fibrosis and cirrhosis with an area under the curve (AUC) of 0.733 (95%CI 0.671-0.795). The diagnostic performance of the NCS was similar in the STELLAR studies (AUC 0.700; 95%CI 0.680-0.730) and a smaller cohort from China (AUC 0.727; 95%CI 0.533-0.921). In the European NAFLD Registry, spanning all histological fibrosis stages, the NCS exhibited an AUC of 0.798 (95%CI 0.766-0.830) to detect cirrhosis. We derived two NCS cut-off values (<64.5 and >79.17) to classify patients at low, intermediate, or high risk for the presence of cirrhosis. Using these cut-offs, further diagnostic workup could be avoided by ruling in or ruling out cirrhosis in approximately half of the patients. Furthermore, NCS identified patients at risk for progression to cirrhosis in the F3 cohort and liver-related outcomes in the F4 cohort. ConclusionThe NCS is a simple tool to improve the identification of compensated cirrhosis within the large group of advanced disease stage and provides prognostic information. Overall, the differentiation of F3 from F4 disease using standard laboratory remains difficult and does not exceed moderate accuracy.Copyright © 2022. Published by Elsevier B.V.

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