The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis
The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis
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DOI：
10.1053/j.gastro.2020.12.003
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发表时间：
2021-04-06
期刊：
影响因子：
29.4
通讯作者：
Stepanova, Maria
中科院分区：
文献类型：
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作者：
Younossi, Zobair M.;Anstee, Quentin M.;Stepanova, Maria
背景与目的：肝纤维化是非酒精性脂肪性肝炎（NASH）死亡的独立预测因子。我们评估了组织学和无创性纤维化检测（NIT）与晚期NASH临床和患者报告结局（PRO）之间的相关性。方法：晚期NASH患者（NASH临床研究网络F3或F4期）入组了4项simtuzumab和selonsertib的多国临床试验。前瞻性收集肝活检样本、NIT结果和PRO（简表-36、慢性肝病非酒精性脂肪性肝炎-NASH、EuroQol-5D和工作效率和活动障碍）。研究结果：共纳入2154例晚期NASH患者：52.5%患有F4 NASH，40%为男性，72%患有2型糖尿病，F4疾病的基线肝硬度为24.1 +/- 14.2 kPa，F3疾病为14.6 +/- 8.0 kPa，F4疾病的基线平均增强型肝纤维化评分为11.4 ± 1.2，F3疾病为10.3 ± 1.0，中位随访时间为16个月。在基线F3疾病的患者中，16.7%的患者经历了疾病进展为肝硬化，而对于F4疾病的患者，7.3%的患者经历了临床事件（39%腹水，24%肝性脑病）;进展的患者具有较高的基线NIT评分（所有P < .0001）。校正基线水平后，F3和F4组中NIT评分的增加也与疾病进展风险增加相关（F3中所有NIT和F4中ELF、NAFLD纤维化评分、纤维化-4（FIB-4）和肝硬度的P <0.01）。发现较高的NIT评分与PRO受损相关：ELF，>= 10.43;非酒精性脂肪性肝病纤维化评分，>= 1.80; Fibrotest评分，>= 0.54;肝硬度，>= 23.4 kPa。在治疗期间，NIT评分降低的患者的PRO评分有所改善，而NIT评分升高的患者的PRO评分恶化（P <0.05）。结论：基线NIT评分及其随时间的变化是晚期NASH患者不良临床和PRO的预测因子。
BACKGROUND & AIM: Fibrosis is an independent predictor of death in nonalcoholic steatohepatitis (NASH). We assessed the associations between histologic and noninvasive tests (NITs) for fibrosis with clinical and patient-reported outcomes (PROs) in advanced NASH. METHODS: Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enrolled in 4 multinational clinical trials of simtuzumab and selonsertib. Liver biopsy samples, NIT results, and PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Impairment) were prospectively collected. RESULTS: A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver stiffness of 24.1 +/- 14.2 kPa in F4 disease and 14.6 +/- 8.0 kPa in F3 disease, baseline mean Enhanced Liver Fibrosis score of 11.4 + 1.2 in F4 disease and 10.3 +/- 1.0 in F3 disease, and a median follow-up of 16 months. Of those with baseline F3 disease, 16.7% experienced disease progression to cirrhosis, whereas for those with F4 disease, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NIT scores (all P < .0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both the F3 and F4 groups (P < .01 for all NITs in F3 and for ELF, NAFLD Fibrosis Score, Fibrosis-4 (FIB-4), and liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF, >= 10.43; Nonalcoholic Fatty Liver Disease Fibrosis Score, >= 1.80; Fibrotest score, >= 0.54; liver stiffness, >= 23.4 kPa. During treatment, patients with decreases in NIT scores experienced improvement of their PRO scores, whereas those with increase in NIT scores had their PRO scores worsen (P < .05). CONCLUSIONS: Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH.