Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4

Background: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients wi...

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Main Authors: Katharina John, Martin Franck, Sherin Al Aoua, Monika Rau, Yvonne Huber, Joern M. Schattenberg, Andreas Geier, Matthias J. Bahr, Heiner Wedemeyer, Klaus Schulze-Osthoff, Heike Bantel
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/11/15/4394
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author Katharina John
Martin Franck
Sherin Al Aoua
Monika Rau
Yvonne Huber
Joern M. Schattenberg
Andreas Geier
Matthias J. Bahr
Heiner Wedemeyer
Klaus Schulze-Osthoff
Heike Bantel
author_facet Katharina John
Martin Franck
Sherin Al Aoua
Monika Rau
Yvonne Huber
Joern M. Schattenberg
Andreas Geier
Matthias J. Bahr
Heiner Wedemeyer
Klaus Schulze-Osthoff
Heike Bantel
author_sort Katharina John
collection DOAJ
description Background: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients with earlier fibrosis stages are at risk of disease progression, emphasizing the need for improved non-invasive risk stratification. Methods: We evaluated whether the apoptosis biomarker M30 can identify patients with fibrotic NASH despite low or intermediate FIB-4 values. Serum M30 levels were assessed by ELISA, and FIB-4 was calculated in an exploration (<i>n</i> = 103) and validation (<i>n</i> = 100) cohort of patients with histologically confirmed NAFLD. Results: The majority of patients with low FIB-4 (cut-off value < 1.3) in the exploration cohort revealed increased M30 levels (>200 U/L) and more than 80% of them had NASH, mostly with fibrosis. NASH was also detected in all patients with intermediate FIB-4 (1.3 to 2.67) and elevated M30, from which ~80% showed fibrosis. Importantly, in the absence of elevated M30, most patients with FIB-4 < 1.3 and NASH showed also no fibrosis. Similar results were obtained in the validation cohort. Conclusions: The combination of FIB-4 with M30 enables a more reliable identification of patients at risk for progressed NAFLD and might, therefore, improve patient stratification.
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spelling doaj.art-0e8eed3c394546f78406722dd46d1ab62023-11-30T22:32:51ZengMDPI AGJournal of Clinical Medicine2077-03832022-07-011115439410.3390/jcm11154394Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4Katharina John0Martin Franck1Sherin Al Aoua2Monika Rau3Yvonne Huber4Joern M. Schattenberg5Andreas Geier6Matthias J. Bahr7Heiner Wedemeyer8Klaus Schulze-Osthoff9Heike Bantel10Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyDivision of Hepatology, Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Internal Medicine I, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Internal Medicine I, University Medical Center Mainz, 55131 Mainz, GermanyDivision of Hepatology, Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, GermanyBrandenburg Medical School, University Hospital Ruppin-Brandenburg, 16816 Neuruppin, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyInterfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyBackground: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients with earlier fibrosis stages are at risk of disease progression, emphasizing the need for improved non-invasive risk stratification. Methods: We evaluated whether the apoptosis biomarker M30 can identify patients with fibrotic NASH despite low or intermediate FIB-4 values. Serum M30 levels were assessed by ELISA, and FIB-4 was calculated in an exploration (<i>n</i> = 103) and validation (<i>n</i> = 100) cohort of patients with histologically confirmed NAFLD. Results: The majority of patients with low FIB-4 (cut-off value < 1.3) in the exploration cohort revealed increased M30 levels (>200 U/L) and more than 80% of them had NASH, mostly with fibrosis. NASH was also detected in all patients with intermediate FIB-4 (1.3 to 2.67) and elevated M30, from which ~80% showed fibrosis. Importantly, in the absence of elevated M30, most patients with FIB-4 < 1.3 and NASH showed also no fibrosis. Similar results were obtained in the validation cohort. Conclusions: The combination of FIB-4 with M30 enables a more reliable identification of patients at risk for progressed NAFLD and might, therefore, improve patient stratification.https://www.mdpi.com/2077-0383/11/15/4394apoptosisbiomarkerfibrosisFIB-4NAFLDNASH
spellingShingle Katharina John
Martin Franck
Sherin Al Aoua
Monika Rau
Yvonne Huber
Joern M. Schattenberg
Andreas Geier
Matthias J. Bahr
Heiner Wedemeyer
Klaus Schulze-Osthoff
Heike Bantel
Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
Journal of Clinical Medicine
apoptosis
biomarker
fibrosis
FIB-4
NAFLD
NASH
title Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
title_full Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
title_fullStr Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
title_full_unstemmed Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
title_short Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4
title_sort non invasive detection of fibrotic nash in nafld patients with low or intermediate fib 4
topic apoptosis
biomarker
fibrosis
FIB-4
NAFLD
NASH
url https://www.mdpi.com/2077-0383/11/15/4394
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