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01-11-2008 | Research Article

A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH)

Authors: Zobair M. Younossi, Mohammed Jarrar, Clare Nugent, Manpreet Randhawa, Mariam Afendy, Maria Stepanova, Nila Rafiq, Zachary Goodman, Vikas Chandhoke, Ancha Baranova

Published in: Obesity Surgery | Issue 11/2008

Abstract

Background

Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH.

Methods

The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen).

Results

Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10⁻⁴, whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10⁻⁴). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10⁻⁴). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis.

Conclusions

Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

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Title: A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH)
Authors: Zobair M. Younossi
Mohammed Jarrar
Clare Nugent
Manpreet Randhawa
Mariam Afendy
Maria Stepanova
Nila Rafiq
Zachary Goodman
Vikas Chandhoke
Ancha Baranova
Publication date: 01-11-2008
Publisher: Springer-Verlag
Published in: Obesity Surgery / Issue 11/2008
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI: https://doi.org/10.1007/s11695-008-9506-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH)

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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Reply to the Letter to the Editor: “A “Biomarker Biopsy” for the Diagnosis of NASH: Promises from CK-18 Fragments” by Yusuf Yilmaz, Engin Ulukaya, Enver Dolar