Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis

Federica Tavaglione; Oveis Jamialahmadi; Antonio De Vincentis; Sami Qadri; Mohammad Erfan Mowlaei; Rosellina Margherita Mancina; Ester Ciociola; Simone Carotti; Giuseppe Perrone; Vincenzo Bruni; Ida Francesca Gallo; Dario Tuccinardi; Cristiana Bianco; Daniele Prati; Silvia Manfrini; Paolo Pozzilli; Antonio Picardi; Marco Caricato; Hannele Yki-Järvinen; Luca Valenti; Umberto Vespasiani-Gentilucci; Stefano Romeo

doi:10.1016/j.cgh.2022.03.044

Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis

Clin Gastroenterol Hepatol. 2023 Jun;21(6):1523-1532.e1. doi: 10.1016/j.cgh.2022.03.044. Epub 2022 Apr 11.

Authors

Federica Tavaglione¹, Oveis Jamialahmadi², Antonio De Vincentis³, Sami Qadri⁴, Mohammad Erfan Mowlaei⁵, Rosellina Margherita Mancina², Ester Ciociola², Simone Carotti⁶, Giuseppe Perrone⁷, Vincenzo Bruni⁸, Ida Francesca Gallo⁸, Dario Tuccinardi⁹, Cristiana Bianco¹⁰, Daniele Prati¹⁰, Silvia Manfrini⁹, Paolo Pozzilli⁹, Antonio Picardi¹¹, Marco Caricato¹², Hannele Yki-Järvinen⁴, Luca Valenti¹³, Umberto Vespasiani-Gentilucci¹⁴, Stefano Romeo¹⁵

Affiliations

¹ Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden. Electronic address: f.tavaglione@unicampus.it.
² Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
³ Internal Medicine Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy; Clinical Lecturer of Internal Medicine, Saint Camillus International University of Health and Medical Sciences, Rome, Italy.
⁴ Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
⁵ Department of Computer & Information Sciences, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
⁶ Research Unit of Microscopic and Ultrastructural Anatomy, Department of Medicine, Campus Bio-Medico University, Rome, Italy; Predictive Molecular Diagnostic Unit, Department of Pathology, Campus Bio-Medico University Hospital, Rome, Italy.
⁷ Predictive Molecular Diagnostic Unit, Department of Pathology, Campus Bio-Medico University Hospital, Rome, Italy; Research Unit of Pathology, Campus Bio-Medico University, Rome, Italy.
⁸ Bariatric Surgery Unit, Campus Bio-Medico University, Rome, Italy.
⁹ Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
¹⁰ Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
¹¹ Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy.
¹² Unit of Colon and Rectal Surgery, Department of General Surgery, Campus Bio-Medico University, Rome, Italy.
¹³ Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.
¹⁴ Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy. Electronic address: u.vespasiani@policlinicocampus.it.
¹⁵ Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy. Electronic address: stefano.romeo@wlab.gu.se.

PMID: 35421583
DOI: 10.1016/j.cgh.2022.03.044

Abstract

Background & aims: Noninvasive assessment of histological features of nonalcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple noninvasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic nonalcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score ≥4, and fibrosis stage ≥2.

Methods: The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in 3 independent European cohorts (Finland, n = 370; Italy, n = 947; England, n = 5368) of individuals at high risk for NAFLD.

Results: The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase, high-density lipoprotein cholesterol, and hemoglobin A1c. The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROC = 0.78 and AUROC = 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cutoffs were 0.10 for sensitivity ≥0.89 (negative predictive value, 0.93) and 0.33 for specificity ≥0.90 (positive predictive value, 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (negative predictive value, 0.99-1) and specificity from 0.73 to 0.94 (positive predictive value, 0.12-0.49) for rule-out and rule-in cutoff, respectively.

Conclusion: FNI is an accurate, simple, and affordable noninvasive score which can be used to screen for fibrotic NASH in individuals with dysmetabolism in primary health care.

Keywords: MAFLD; Metabolic Dysfunction-associated Fatty Liver Disease; Noninvasive tests; Obesity; Type 2 Diabetes.

MeSH terms

Biopsy
Fibrosis
Humans
Liver / pathology
Liver Cirrhosis / diagnosis
Liver Cirrhosis / pathology
Non-alcoholic Fatty Liver Disease* / diagnosis
Non-alcoholic Fatty Liver Disease* / pathology
Obesity, Morbid*
Predictive Value of Tests