Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, P.R. China.
Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P.R. China.
Clin Chem Lab Med. 2021 Jan 8;59(6):1087-1097. doi: 10.1515/cclm-2020-1588. Print 2021 May 26.
Liver cirrhosis (LC) is the end-stage of fibrosis in chronic liver diseases, non-invasive early detection of liver fibrosis (LF) is particularly essential for therapeutic decision. Aberrant glycosylation of glycoproteins has been demonstrated to be closely related to liver abnormalities.
This study was designed to enroll a total of 1,565 participants with LC/LF, chronic hepatitis virus (CHB) and healthy controls. Fibrosis was confirmed by liver biopsy. Using capillary electrophoresis N-glycan fingerprint (NGFP) analysis, we developed a nomogram algorithm (FIB-G) to discriminate LC from non-cirrhotic subjects.
The FIB-G demonstrated good diagnostic performances in identifying LC with the area under the curve (AUC) 0.895 (95%CI: 0.857-0.915). Furthermore, the diagnostic efficiencies of FIB-G were superior to that of log (P2/P8), procollagen III N-terminal (PIIINP), type IV collage (IV-C), laminin (LN), hyaluronic acid (HA), aspartate transaminase to platelets ratio index (APRI), and FIB-4 when detecting significant fibrosis (S0-1 vs. S2-4, AUC: 0.787, 95%CI: 0.701-0.873), severe fibrosis (S0-2 vs. S3-4, AUC: 0.844, 95%CI: 0.763-0.924), and LC (S0-3 vs. S4, AUC: 0.773, 95%CI: 0.667-0.880). Besides, changes of FIB-G were associated well with the regression of fibrosis and liver function Child-Pugh classification.
FIB-G is an accurate multivariant N-glycomic algorithm for LC prediction and fibrosis progression/regression monitoring. The high throughput feasible NGFP using only 2 μL of serum could help physicians make the more precise non-invasive staging of LF or cirrhosis and reduce the need for invasive liver biopsy.
肝硬化（LC）是慢性肝病纤维化的终末期，早期无创性检测肝纤维化（LF）对治疗决策尤为重要。糖蛋白的异常糖基化已被证明与肝脏异常密切相关。
本研究共纳入 1565 名 LC/LF、慢性乙型肝炎病毒（CHB）和健康对照者。纤维化通过肝活检证实。使用毛细管电泳 N-糖基化指纹（NGFP）分析，我们开发了一个列线图算法（FIB-G）来区分 LC 与非肝硬化患者。
FIB-G 在识别 LC 时具有良好的诊断性能，曲线下面积（AUC）为 0.895（95%CI：0.857-0.915）。此外，FIB-G 的诊断效率优于 log（P2/P8）、III 型前胶原氨基端肽（PIIINP）、IV 型胶原（IV-C）、层粘连蛋白（LN）、透明质酸（HA）、天门冬氨酸氨基转移酶血小板比值指数（APRI）和 FIB-4，用于检测显著纤维化（S0-1 与 S2-4，AUC：0.787，95%CI：0.701-0.873）、严重纤维化（S0-2 与 S3-4，AUC：0.844，95%CI：0.763-0.924）和 LC（S0-3 与 S4，AUC：0.773，95%CI：0.667-0.880）。此外，FIB-G 的变化与纤维化的消退和肝功能 Child-Pugh 分级密切相关。
FIB-G 是一种准确的多变量糖基化算法，可用于预测 LC 和监测纤维化进展/消退。仅使用 2μL 血清即可进行高通量的 NGFP，有助于医生更准确地对 LF 或肝硬化进行非侵入性分期，并减少对肝活检的需求。
