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

Background & 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.