Serum immunoreactive collagen IV detected by monoclonal antibodies as a marker of severe fibrosis in patients with non-alcoholic fatty liver disease

J Gastrointestin Liver Dis. 2015 Mar;24(1):61-8. doi: 10.15403/jgld.2014.1121.yad.

Abstract

Background and aims: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We evaluated serum collagen IV as a direct non-invasive marker of severe liver fibrosis in NAFLD.

Methods: The study included 148 NAFLD and 187 chronic hepatitis C patients in whom histological severity of liver fibrosis was evaluated. The utility of serum collagen IV measured by immune-mediated agglutination using two types of monoclonal antibodies for distinguishing severe fibrosis (≥ stage 3 and ≥ F3) from non-to-moderate fibrosis in NAFLD or chronic hepatitis C was assessed in comparison to serum hyaluronic acid or other indirect fibrosis markers.

Results: Multiple logistic regression analysis showed that serum collagen IV was significantly associated with severe fibrosis in NAFLD (odds ratio: 1.21, p<0.001) but not in chronic hepatitis C. For distinguishing severe fibrosis in NAFLD, collagen IV showed the largest area under the receiver-operating characteristic curve (0.827, 95%CI: 0.746-0.908) followed by FIB-4 (0.805, 95%CI: 0.728-0.890); in chronic hepatitis C, those for FIB-4 (0.813, 95%CI: 0.748-0.878) and collagen IV (0.770, 95%CI: 0.683-0.857) were the largest and smallest, respectively. To detect severe fibrosis in NAFLD, a cutoff of collagen IV > 177 exhibited 77.1% sensitivity, 84.0% specificity, 76.5% positive predictive value, and 84.0% negative predictive value. Combined with a cutoff of FIB-4 > 2.09, the negative and positive predictive values, and specificity for detecting severe fibrosis in NAFLD increased further.

Conclusion: Collagen IV is a reliable marker for distinguishing severe liver fibrosis from non-to-moderate fibrosis in NAFLD but not chronic hepatitis C.

Publication types

  • Evaluation Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal / immunology*
  • Area Under Curve
  • Biomarkers / blood
  • Collagen Type IV / blood*
  • Collagen Type IV / immunology
  • Diagnosis, Differential
  • Female
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / diagnosis*
  • Hepatitis C, Chronic / immunology
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / immunology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / immunology
  • Odds Ratio
  • Predictive Value of Tests
  • ROC Curve
  • Retrospective Studies
  • Serologic Tests*
  • Severity of Illness Index

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Collagen Type IV