Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Division of Hepatology, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Liver Int. 2023 Dec;43(12):2668-2679. doi: 10.1111/liv.15686. Epub 2023 Aug 3.
The presence of significant liver fibrosis associated with non-alcoholic steatohepatitis (NASH) is regarded as the major prognostic factor in non-alcoholic fatty liver disease (NAFLD). Identification of patients at risk for NASH with significant fibrosis is therefore important. Although the established fibrosis score FIB-4 is suitable to exclude advanced fibrosis, it does not allow the prediction of significant fibrosis in NAFLD patients. We therefore evaluated whether the hepatokine fibroblast growth factor 21 (FGF21), a regulator of glucose and lipid metabolism, might identify 'at-risk NASH' in NAFLD.
FGF21 levels were assessed by enzyme-linked immunosorbent assay in sera from an exploration (n = 137) and a validation (n = 88) cohort of biopsy-proven NAFLD patients with different disease activity and fibrosis stages. In addition, we evaluated whether the use of FGF21 could improve risk stratification in NAFLD patients with low (<1.3) or intermediate (1.3-2.67) FIB-4.
FGF21 levels could significantly discriminate between NASH and non-alcoholic fatty liver (NAFL) patients, even in the absence of diabetes. Moreover, patients with NASH and fibrosis ≥F2 showed significantly higher FGF21 levels compared to NAFLD patients without significant fibrosis. Significantly elevated FGF21 levels could even be detected in NAFLD patients with NASH and significant fibrosis despite low or intermediate FIB-4.
Serological FGF21 detection might allow the identification of NAFLD patients at risk and improves patient stratification in combination with FIB-4.
非酒精性脂肪性肝炎（NASH）相关的显著肝纤维化被认为是非酒精性脂肪性肝病（NAFLD）的主要预后因素。因此，识别存在 NASH 且有显著纤维化风险的患者非常重要。尽管已建立的纤维化评分 FIB-4 适用于排除晚期纤维化，但它不能预测 NAFLD 患者的显著纤维化。因此，我们评估了作为葡萄糖和脂质代谢调节剂的肝源细胞因子成纤维细胞生长因子 21（FGF21）是否可以识别“存在 NASH 风险”的 NAFLD 患者。
通过酶联免疫吸附试验检测了经肝活检证实的不同疾病活动度和纤维化分期的 NAFLD 患者的探索（n=137）和验证（n=88）队列的血清中 FGF21 水平。此外，我们还评估了在 FIB-4 低值（<1.3）或中值（1.3-2.67）的 NAFLD 患者中使用 FGF21 是否可以改善风险分层。
即使在没有糖尿病的情况下，FGF21 水平也可以显著区分 NASH 和非酒精性脂肪肝（NAFL）患者。此外，纤维化≥F2 的 NASH 患者的 FGF21 水平明显高于无显著纤维化的 NAFLD 患者。即使在 FIB-4 低值或中值的情况下，NASH 和显著纤维化的 NAFLD 患者也可以检测到明显升高的 FGF21 水平。
血清 FGF21 检测可能可以识别存在风险的 NAFLD 患者，并与 FIB-4 联合使用改善患者分层。
