非酒精性脂肪性肝炎所致晚期纤维化患者的组织学和非侵入性检查与不良临床和患者报告结局的相关性。
The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis.
机构信息
Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia.
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; Newcastle National Institute for Health Research Biomedical Research Centre, Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, Newcastle Upon Tyne, UK.
出版信息
Gastroenterology. 2021 Apr;160(5):1608-1619.e13. doi: 10.1053/j.gastro.2020.12.003. Epub 2020 Dec 8.
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. (ClinicalTrials.gov, Numbers NCT01672866, NCT01672879, NCT03053050, and NCT03053063).
背景与目的
纤维化是非酒精性脂肪性肝炎（NASH）患者死亡的独立预测因素。本研究旨在评估组织学和非侵入性检测（NIT）与晚期 NASH 的临床和患者报告结局（PRO）之间的相关性。
方法
4 项针对 simtuzumab 和 selonsertib 的多中心临床试验共纳入 2154 例晚期 NASH 患者（NASH 临床研究网络分期 F3 或 F4）。前瞻性收集肝活检样本、NIT 结果和 PRO（36 项简明健康调查问卷、慢性肝病问卷-NASH、EuroQol-5D 和工作效率及活动障碍）。
结果
共纳入 2154 例晚期 NASH 患者：52.5%为 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±14.2kPa，F3 疾病为 14.6±8.0kPa，F4 疾病的基线平均增强型肝脏纤维化评分（ELF）为 11.4±1.2，F3 疾病为 10.3±1.0，中位随访时间为 16 个月。基线 F3 疾病患者中，16.7%出现疾病进展为肝硬化，而 F4 疾病患者中，7.3%出现临床事件（39%腹水，24%肝性脑病）；进展患者的基线 NIT 评分更高（均 P<.0001）。在调整基线水平后，F3 和 F4 两组中，NIT 评分的增加也与疾病进展风险增加相关（所有 NIT 在 F3 中，以及在 ELF、非酒精性脂肪性肝病纤维化评分、纤维化 4 指数（FIB-4）和 F4 中的肝硬度的 P<.01）。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，≥23.4kPa。在治疗过程中，NIT 评分降低的患者 PRO 评分得到改善，而 NIT 评分升高的患者 PRO 评分恶化（P<.05）。
结论
基线 NIT 评分及其随时间的变化可预测晚期 NASH 患者的不良临床和 PRO。（临床试验.gov，注册号 NCT01672866、NCT01672879、NCT03053050 和 NCT03053063）。
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