A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis.
BACKGROUND
Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis.


OBJECTIVE
This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables.


METHODS
Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated.


RESULTS
Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65-M30 (necrosis) [AUC: 0.81, 95% CI, 0.70-0.89, 300 p value <9E 301 (-06)]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68-0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70-0.89; p value, 0.000062].


CONCLUSIONS
This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.
Younossi
Zobair M
ZM
Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. zobair.younossi@inova.org
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Sandra
S
Rafiq
Nila
N
Birerdinc
Aybike
A
Stepanova
Maria
M
Hossain
Noreen
N
Afendy
Arian
A
Younoszai
Zahra
Z
Goodman
Zachary
Z
Baranova
Ancha
A
D054392:Adipokines / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D053538:Keratin-18 / Q000097:blood; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011379:Prognosis; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D054392:Adipokines; D015415:Biomarkers; D001786:Blood Glucose; D053538:Keratin-18; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid