Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
Center for the Study of Chronic Illness and Disability, George Mason University, Fairfax, Virginia.
Liver Int. 2019 Sep;39(9):1631-1640. doi: 10.1111/liv.14115. Epub 2019 May 3.
BACKGROUND & AIMS: Chronic hepatitis C (CHC) has a negative impact on patient-reported outcomes (PROs). Although most CHC patients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHC patients who achieve SVR.
Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed-dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form-36 (SF-36), Fatigue Severity Scale (FSS), Beck Depression Inventory-II (BDI-II), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow-up week 24.
Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF-36 physical health summary score (rho = -0.34, P < 0.05), SF-36 physical functioning (rho = -0.34, P < 0.05), SF-36 bodily pain (rho = -0.39, P < 0.05) and FACIT-F physical well-being (rho = -0.54, P < 0.001). Changes in emotional well-being (FACIT-F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = -0.4, P = 0.01, and rho = -0.35, P < 0.05 respectively).
These data indicate relationships between PROs and serum biomarkers pre- and post-SVR in CHC. These concomitant changes may have important clinical relevance.
慢性丙型肝炎（CHC）对患者报告的结局（PROs）有负面影响。虽然大多数达到持续病毒学应答（SVR）的 CHC 患者的 PRO 评分有所改善，但仍有部分患者的 PRO 持续受损。本研究旨在探究达到 SVR 的 CHC 患者的血清生物标志物（选择的神经递质和细胞因子）是否与 PRO 变化相关。
该研究数据来自一项索磷布韦/维帕他韦固定剂量复方制剂的前瞻性临床试验。无肝硬化的慢性基因型 1 HCV 受试者（N=40，年龄：45.3±11.5，48%为男性，90%为白人）接受了 12 周的开放标签治疗，97%的患者达到了 SVR24。PRO 问卷包括 36 项简短健康调查问卷（SF-36）、疲劳严重程度量表（FSS）、贝克抑郁量表-II（BDI-II）、慢性丙型肝炎问卷（CLDQ-HCV）和慢性疾病治疗疲劳功能评估（FACIT-F）。血清用于检测选定的神经递质和细胞因子。数据在基线和随访 24 周时收集。
生理健康的变化与几种生物标志物的变化相关。BDNF 与 SF-36 生理健康总分（rho=-0.34，P<0.05）、SF-36 生理功能（rho=-0.34，P<0.05）、SF-36 躯体疼痛（rho=-0.39，P<0.05）和 FACIT-F 生理健康评分（rho=-0.54，P<0.001）呈负相关。情绪健康（FACIT-F）的变化与血清 5-羟色胺（rho=0.34，P<0.05）的变化呈正相关，但与 GABA 和 BDNF 的变化呈负相关（rho=-0.4，P=0.01，和 rho=-0.35，P<0.05）。
这些数据表明 CHC 患者在 SVR 前后的 PROs 和血清生物标志物之间存在关系。这些伴随的变化可能具有重要的临床意义。
