A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis

Obes Surg. 2011 Apr;21(4):431-9. doi: 10.1007/s11695-010-0204-1.

Abstract

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.

Aim: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adipokines / blood
  • Adult
  • Biomarkers / blood*
  • Biopsy
  • Blood Glucose / analysis
  • Fatty Liver / blood
  • Fatty Liver / complications
  • Fatty Liver / diagnosis
  • Female
  • Humans
  • Hyaluronic Acid / blood
  • Keratin-18 / blood
  • Liver / pathology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Models, Biological
  • Non-alcoholic Fatty Liver Disease
  • Peptide Fragments / blood
  • Procollagen / blood
  • Prognosis
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-1 / blood

Substances

  • Adipokines
  • Biomarkers
  • Blood Glucose
  • Keratin-18
  • Peptide Fragments
  • Procollagen
  • Tissue Inhibitor of Metalloproteinase-1
  • procollagen Type III-N-terminal peptide
  • Hyaluronic Acid