UCL Institute of Liver & Digestive Health, Centre for Hepatology, Division of Medicine, University College London, London, UK.
Hepatology. 2013 Jan;57(1):103-11. doi: 10.1002/hep.26030.
Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87.
PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH.
肝活检是非酒精性脂肪性肝病(NAFLD)中检测非酒精性脂肪性肝炎(NASH)的参考标准。本研究旨在确定无显著纤维化的 NASH 患者的生物标志物。本研究共纳入来自两个中心的 172 例经活检证实的 NAFLD 患者。其中 84 例来自单一中心的患者被纳入推导队列,88 例来自第二中心的患者被纳入验证队列。检测了候选纤维化和炎症标志物以及血液学和生化标志物。在无晚期纤维化的患者中,III 型前胶原末端肽(PIIINP)是两个队列中唯一与组织学诊断 NASH 相关的标志物。PIIINP 还与总的 NAFLD 活动评分(NAS)及其组成成分相关(P<0.001)。在纤维化程度为 F0-2 和 F0-3 的患者中,PIIINP 区分 NASH 和单纯性脂肪变性(SS)的受试者工作特征曲线(AUROC)下面积分别为 0.77-0.82 和 0.82-0.84。在有晚期纤维化的患者中,PIIINP 升高,其中绝大多数患有 NASH。当纳入来自两个队列的所有纤维化程度的患者时,PIIINP 能够区分 SS 患者和 NASH 或伴有 NASH 的晚期纤维化患者,AUROC 为 0.85-0.87。
PIIINP 可区分 SS 和 NASH 或晚期纤维化。在这种情况下使用单一生物标志物将有助于临床检测少数患有 NASH 或与 NASH 相关的晚期纤维化的 NAFLD 患者。