Park Sunhee, Abdi Tsion, Gentry Mark, Laine Loren
Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA.
VA Connecticut Healthcare System, West Haven, Connecticut, USA.
Am J Gastroenterol. 2016 Dec;111(12):1692-1701. doi: 10.1038/ajg.2016.418. Epub 2016 Oct 11.
Endoscopic remission in ulcerative colitis (UC) is associated with improved clinical outcomes. We assessed whether histological remission predicts clinical outcomes, estimated the magnitude of effect, and determined whether histological remission provides additional prognostic utility beyond clinical or endoscopic remission.
Bibliographic databases were searched for studies in inflammatory bowel disease providing baseline histological status and relation to an outcome of clinical relapse or exacerbation. Our primary analysis compared the proportion of patients with study-defined histological remission vs. the proportion with histological activity who developed clinical relapse/exacerbation. Additional analyses compared the proportion with relapse/exacerbation for the presence vs. absence of different histological features and for histological remission vs. endoscopic remission and clinical remission. A fixed-effect model was used for meta-analysis, with a random-effects model if statistical heterogeneity was present.
Fifteen studies met inclusion criteria. The major methodological shortcoming was lack of blinding of the assessor of clinical relapse/exacerbation to baseline histological status in 13 of the 15 studies. Relapse/exacerbation was less frequent with baseline histological remission vs. histological activity (relative risk (RR)=0.48, 95% confidence interval (CI) 0.39-0.60) and vs. baseline clinical and endoscopic remission (RR=0.81, 95% CI 0.70-0.94). Relapse/exacerbation was also less common in the absence vs. presence of specific histological features: neutrophils in epithelium (RR=0.32, 95% CI 0.23-0.45), neutrophils in lamina propria (RR=0.43, 95% CI 0.32-0.59), crypt abscesses (RR=0.38, 95% CI 0.27-0.54), eosinophils in the lamina propria (RR=0.43, 95% CI 0.21-0.91), and chronic inflammatory cell infiltrate (RR=0.28, 95% CI 0.10-0.75). Histological remission was present in 964 (71%) of the 1360 patients with combined endoscopic and clinical remission at baseline.
UC patients with histological remission have a significant 52% RR reduction in clinical relapse/exacerbation compared with those with histological activity. Histological remission is also superior to endoscopic and clinical remission in predicting clinical outcomes. As ~30% of patients with endoscopic and clinical remission still have histological activity, addition of histological status as an end point in clinical trials or practice has the potential to improve clinical outcomes.
溃疡性结肠炎（UC）的内镜缓解与临床结局改善相关。我们评估了组织学缓解是否能预测临床结局，估计了效应大小，并确定组织学缓解在临床或内镜缓解之外是否具有额外的预后价值。
检索文献数据库，查找有关炎症性肠病的研究，这些研究提供了基线组织学状态以及与临床复发或病情加重结局的关系。我们的主要分析比较了达到研究定义的组织学缓解的患者比例与发生临床复发/病情加重的组织学活动患者比例。额外分析比较了有无不同组织学特征、组织学缓解与内镜缓解及临床缓解时复发/病情加重的比例。采用固定效应模型进行荟萃分析，若存在统计异质性则采用随机效应模型。
15项研究符合纳入标准。主要方法学缺陷是15项研究中有13项临床复发/病情加重评估者对基线组织学状态未设盲。与组织学活动相比，基线组织学缓解时复发/病情加重的频率较低（相对风险（RR）=0.48，95%置信区间（CI）0.39 - 0.60），与基线临床和内镜缓解相比也是如此（RR = 0.81，95% CI 0.70 - 0.94）。在无特定组织学特征与有特定组织学特征的情况下，复发/病情加重也较少见：上皮内中性粒细胞（RR = 0.32，95% CI 0.23 - 0.45）、固有层中性粒细胞（RR = 0.43，95% CI 0.32 - 0.59）、隐窝脓肿（RR = 0.38，95% CI 0.27 - 0.54）、固有层嗜酸性粒细胞（RR = 0.43，95% CI 0.21 - 0.91）以及慢性炎症细胞浸润（RR = 0.28，95% CI 0.10 - 0.75）。在基线时内镜和临床联合缓解的1360例患者中，964例（71%）存在组织学缓解。
与有组织学活动的UC患者相比，组织学缓解的UC患者临床复发/病情加重的相对风险显著降低52%。在预测临床结局方面，组织学缓解也优于内镜和临床缓解。由于约30%内镜和临床缓解的患者仍有组织学活动，在临床试验或实践中增加组织学状态作为一个终点有可能改善临床结局。
