Boehringer Ingelheim Pharma GmbH, Biberach, Germany.
Boehringer Ingelheim International GmbH, Ingelheim, Germany.
J Mol Med (Berl). 2024 Jul;102(7):841-858. doi: 10.1007/s00109-024-02448-2. Epub 2024 May 16.
Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it can lead to decompensation events such as ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma (HCC). In addition, an increased risk for cardiovascular events has been demonstrated in patients with NASH. Pharmacological treatments for NASH cirrhosis are not yet available, one of the reasons being the lack in surrogate endpoints available in clinical trials of NASH cirrhosis. The feasibility of non-invasive prognostic biomarkers makes them interesting candidates as possible surrogate endpoints if their change following treatment would result in better outcomes for patients in future clinical trials of NASH cirrhosis. In this systematic literature review, a summary of the available literature on the prognostic performance of non-invasive biomarkers in terms of cardiovascular events, liver-related events, and mortality is outlined. Due to the scarcity of data specific for NASH cirrhosis, this review includes studies on NAFLD whose evaluation focuses on cirrhosis. Our search strategy identified the following non-invasive biomarkers with prognostic value in studies of NASH patients: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), enhanced liver fibrosis (ELF™), BARD (BMI, AST/ALT (alanine aminotransferase) ratio, diabetes), Hepamet Fibrosis Score (HFS), liver enzymes (AST + ALT), alpha-fetoprotein, platelet count, neutrophil to lymphocyte ratio (NLR), Lysyl oxidase-like (LOXL) 2, miR-122, liver stiffness, MEFIB (liver stiffness measured with magnetic resonance elastography (MRE) + FIB-4), and PNPLA3 GG genotype. The aim of the present systematic literature review is to provide the reader with a summary of the non-invasive biomarkers with prognostic value in NASH cirrhosis and give an evaluation of their utility as treatment monitoring biomarkers in future clinical trials.
非酒精性脂肪性肝炎（NASH）导致的肝硬化是一种危及生命的疾病，其发病率在全球范围内呈上升趋势。尽管其症状不特异，但可导致腹水、肝性脑病、静脉曲张出血和肝细胞癌（HCC）等失代偿事件。此外，NASH 患者发生心血管事件的风险增加已得到证实。目前尚无治疗 NASH 肝硬化的药物，其原因之一是 NASH 肝硬化临床试验中缺乏替代终点。非侵入性预后生物标志物的可行性使其成为可能的替代终点候选物，如果它们在治疗后发生变化，可能会为未来 NASH 肝硬化临床试验中的患者带来更好的结果。在这项系统文献综述中，概述了有关非侵入性生物标志物在心血管事件、肝脏相关事件和死亡率方面的预后性能的现有文献摘要。由于专门针对 NASH 肝硬化的数据稀缺，本综述包括了对 NASH 评估侧重于肝硬化的非酒精性脂肪性肝病的研究。我们的检索策略确定了以下具有 NASH 患者预后价值的非侵入性生物标志物：非酒精性脂肪性肝病纤维化评分（NFS）、纤维化-4（FIB-4）、天门冬氨酸氨基转移酶（AST）与血小板比值指数（APRI）、增强型肝纤维化（ELF™）、BARD（BMI、AST/ALT（丙氨酸氨基转移酶）比值、糖尿病）、Hepamet 纤维化评分（HFS）、肝酶（AST+ALT）、甲胎蛋白、血小板计数、中性粒细胞与淋巴细胞比值（NLR）、赖氨酰氧化酶样 2（LOXL2）、miR-122、肝硬度、MEFIB（磁共振弹性成像（MRE）测量的肝硬度+FIB-4）和 PNPLA3 GG 基因型。本系统文献综述的目的是为读者提供 NASH 肝硬化具有预后价值的非侵入性生物标志物的摘要，并评估它们作为未来临床试验中治疗监测生物标志物的效用。
