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.
Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. zobair.younossi@inova.org
Zobair M
ZM
Younossi
Sandra
S
Page
Nila
N
Rafiq
Aybike
A
Birerdinc
Maria
M
Stepanova
Noreen
N
Hossain
Arian
A
Afendy
Zahra
Z
Younoszai
Zachary
Z
Goodman
Ancha
A
Baranova
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