Evaluating future risk of NAFLD fibrosis in adolescents: prediction and decision curve analysis

of interstitial matrix collagens is observed during advanced fibrosis.The role of type VII collagen in liver fibrosis is unknown.The aim of this study was to investigate the role of type VII collagen using a collagen neoepitope technology in relation to fibrosis development in NAFLD patients.Method: Degradation of type VII collagen was assessed by the novel neoepitope marker, C7M, developed by Nordic Bioscience A/S, in serum samples from 140 NAFLD patients with biopsy confirmed liver fibrosis F0-F4 and NAS 0-7 in a cross-sectional study design.Histopathological staging of fibrosis, steatosis, hepatocyte ballooning and lobular inflammation was scored according to the Kleiner scoring system.Results: Patients had median age of 53.5 (IQR 43-60) years and median BMI of 32.2 kg/m 2 (IQR 29.0-36.1) of which 74 (53%) were male ( p = 0.499).Serum C7M significantly correlated with the NAS (r = 0.255; p = 0.003), the grade of hepatocyte ballooning (r = 0.278; p = 0.001), and steatosis (r = 0.285; p < 0.001), but not the degree of lobular inflammation (r = 0.161; p = 0.065) or the histological fibrosis stage (r = -0.005;p = 0.962).C7M was significantly elevated in patients with NAS ≥3 compared to NAS ≤2 ( p < 0.001).A 30% and 18% increase in C7M was observed from hepatocyte ballooning grade 0 to 1-2 ( p = 0.001) and from steatosis grade 0-1 to 2-3 ( p = 0.004), respectively.In the same cohort, the levels of the fibrogenic collagen marker, PRO-C3, was increased in the population with advanced vs early fibrosis ( p < 0.0001), as well as in patients with steatosis ( p = 0.0001), hepatocyte ballooning ( p = 0.0001), and lobular inflammation ( p < 0.0001).Conclusion: Degradation of type VII collagen may be an early indicator of increased protease activity, related to linkage disruption of the ECM structure between basement membrane and interstitial matrix collagens in liver fibrosis development in patients with NAFLD.