Serum Immunoreactive Collagen IV detected by Monoclonal Antibodies as a Marker of Severe Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
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Yuta Aida, Hiroshi Abe, Yoichi Tomita, Tomohisa Nagano, Nobuyoshi Seki, Tomonori Sugita, Munenori Itagaki, Haruya Ishiguro, Satoshi Sutoh, Yoshio Aizawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506,
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.
Key words: non-alcoholic fatty liver disease - non-alcoholic steatohepatitis - collagen IV - FIB-4 - hepatitis C virus - liver fibrosis