Fabio Nascimbeni1, Pierre Bedossa2, Larysa Fedchuk3, Raluca Pais4, Frédéric Charlotte5, Pascal Lebray3, Thierry Poynard3, Vlad Ratziu6. 1. Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; Department of Hepatology and Gastroenterology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France; Institute for Cardiometabolism and Nutrition (ICAN). 2. LiverPat Paris France and Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, UK. 3. Department of Hepatology and Gastroenterology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France. 4. Department of Hepatology and Gastroenterology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France; Institute for Cardiometabolism and Nutrition (ICAN). 5. Pathology Department, Pitié-Salpêtrière Hospital, Paris, France. 6. Department of Hepatology and Gastroenterology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France; INSERM UMRS 1138, Centre de Recherche des Cordeliers, Paris, France; Institute for Cardiometabolism and Nutrition (ICAN). Electronic address: vlad.ratziu@inserm.fr.
Abstract
BACKGROUND & AIMS: Histological classifications used to diagnose/stage non-alcoholic fatty liver disease (NAFLD) are based on morphology, with undetermined clinical correlates and relevance. We assessed the clinical relevance of the fatty liver inhibition of progression (FLIP) algorithm and the steatosis, activity, and fibrosis (SAF) scoring system. METHODS: One hundred and forty consecutive patients with suspected NAFLD and a separate validation cohort of 78 patients enrolled in a therapeutic trial, all with central reading of liver biopsy, were included. FLIP and SAF were used to categorize patients with non-alcoholic steatohepatitis (NASH), non-NASH NAFLD (NAFL), or non-NAFLD. The SAF activity score assessed hepatocyte ballooning and lobular inflammation; a histologically severe disease was defined as a SAF activity score of ≥3 and/or bridging fibrosis or cirrhosis. Clinical, biochemical, and metabolic data were analyzed in relation to histology. RESULTS: Patients with NASH according to the FLIP algorithm had a clinical profile distinct from those with NAFL, with a higher prevalence of metabolic risk factors (increased body mass index [BMI], central obesity, serum glucose, and glycated hemoglobin), more severe insulin resistance (fasting insulin and homeostasis model assessment for insulin resistance [HOMA-IR] values), and higher levels of aminotransferases. Similar findings were documented for patients with severe disease vs. those without. Positive linear trends existed between NASH or severe disease and increasing BMI and HOMA-IR. There was a strong association between liver fibrosis and NASH or SAF-defined scores of activity. Patients with either significant or bridging fibrosis overwhelmingly had NASH, and bridging fibrosis most often coexisted with severe activity. CONCLUSIONS: The FLIP algorithm/SAF score, although based on purely morphological grounds, are clinically relevant, as they identify patients with distinct clinical and biological profiles of disease severity. Disease activity in NAFLD is associated with fibrosis severity. LAY SUMMARY: The examination of liver tissue under the microscope (histology) serves to define the type and severity of non-alcoholic fatty liver disease morphologically, and is also used to determine improvement in therapeutic or natural history clinical trials. The FLIP algorithm/SAF classification is a new histological classification well validated on morphological but not clinical grounds. Here, we demonstrate that different disease categories defined by the FLIP/SAF classification correspond to entities of different clinical and biological severity. We also show a strong association between the activity of steatohepatitis (defined histologically) and the amount of fibrotic scar.
BACKGROUND & AIMS: Histological classifications used to diagnose/stage non-alcoholic fatty liver disease (NAFLD) are based on morphology, with undetermined clinical correlates and relevance. We assessed the clinical relevance of the fatty liver inhibition of progression (FLIP) algorithm and the steatosis, activity, and fibrosis (SAF) scoring system. METHODS: One hundred and forty consecutive patients with suspected NAFLD and a separate validation cohort of 78 patients enrolled in a therapeutic trial, all with central reading of liver biopsy, were included. FLIP and SAF were used to categorize patients with non-alcoholic steatohepatitis (NASH), non-NASHNAFLD (NAFL), or non-NAFLD. The SAF activity score assessed hepatocyte ballooning and lobular inflammation; a histologically severe disease was defined as a SAF activity score of ≥3 and/or bridging fibrosis or cirrhosis. Clinical, biochemical, and metabolic data were analyzed in relation to histology. RESULTS:Patients with NASH according to the FLIP algorithm had a clinical profile distinct from those with NAFL, with a higher prevalence of metabolic risk factors (increased body mass index [BMI], central obesity, serum glucose, and glycated hemoglobin), more severe insulin resistance (fasting insulin and homeostasis model assessment for insulin resistance [HOMA-IR] values), and higher levels of aminotransferases. Similar findings were documented for patients with severe disease vs. those without. Positive linear trends existed between NASH or severe disease and increasing BMI and HOMA-IR. There was a strong association between liver fibrosis and NASH or SAF-defined scores of activity. Patients with either significant or bridging fibrosis overwhelmingly had NASH, and bridging fibrosis most often coexisted with severe activity. CONCLUSIONS: The FLIP algorithm/SAF score, although based on purely morphological grounds, are clinically relevant, as they identify patients with distinct clinical and biological profiles of disease severity. Disease activity in NAFLD is associated with fibrosis severity. LAY SUMMARY: The examination of liver tissue under the microscope (histology) serves to define the type and severity of non-alcoholic fatty liver disease morphologically, and is also used to determine improvement in therapeutic or natural history clinical trials. The FLIP algorithm/SAF classification is a new histological classification well validated on morphological but not clinical grounds. Here, we demonstrate that different disease categories defined by the FLIP/SAF classification correspond to entities of different clinical and biological severity. We also show a strong association between the activity of steatohepatitis (defined histologically) and the amount of fibrotic scar.
Authors: Mohammed Eslam; Shiv K Sarin; Vincent Wai-Sun Wong; Jian-Gao Fan; Takumi Kawaguchi; Sang Hoon Ahn; Ming-Hua Zheng; Gamal Shiha; Yusuf Yilmaz; Rino Gani; Shahinul Alam; Yock Young Dan; Jia-Horng Kao; Saeed Hamid; Ian Homer Cua; Wah-Kheong Chan; Diana Payawal; Soek-Siam Tan; Tawesak Tanwandee; Leon A Adams; Manoj Kumar; Masao Omata; Jacob George Journal: Hepatol Int Date: 2020-10-01 Impact factor: 6.047
Authors: Abraham S Meijnikman; Mark Davids; Hilde Herrema; Omrum Aydin; Valentina Tremaroli; Melany Rios-Morales; Han Levels; Sjoerd Bruin; Maurits de Brauw; Joanne Verheij; Marleen Kemper; Adriaan G Holleboom; Maarten E Tushuizen; Thue W Schwartz; Jens Nielsen; Dees Brandjes; Eveline Dirinck; Jonas Weyler; An Verrijken; Christophe E M De Block; Luisa Vonghia; Sven Francque; Ulrich Beuers; Victor E A Gerdes; Fredrik Bäckhed; Albert K Groen; Max Nieuwdorp Journal: Nat Med Date: 2022-10-10 Impact factor: 87.241