Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
Department of Hepatopathology, Institute of Liver and Biliary Sciences, New Delhi, India.
Virchows Arch. 2018 Apr;472(4):667-675. doi: 10.1007/s00428-018-2330-4. Epub 2018 Mar 7.
Baseline clinical and biochemical parameters fail to predict non-response to steroids in severe alcoholic hepatitis patients. Liver biopsy features have not been adequately assessed for predicting response to steroid therapy in severe alcoholic hepatitis. We aimed to identify histological parameters, which can predict steroid response in severe alcoholic hepatitis (SAH). We analyzed histological data of 107 SAH patients (71 in a derivative and 36 in a validation cohort) who presented within 4 weeks after inset of jaundice and were prospectively treated with steroids (40 mg/day). Histopathological parameters were semi-quantitatively scored in the pre-therapy biopsies in the derivative cohort, and a histological scoring system of SAH was developed which differentiated between steroid responders (Lille score < 0.45 at day 7) and non-responders. Seventeen of the 71 (24%) patients in the derivation cohort and 9 of 36 (25%) in the validation cohort were non-responders to steroids. In the derivation cohort, in comparison to responders, non-responders had higher severity of ballooning degeneration (BD) (mean 3.87 ± 0.91 versus 2.92 ± 1.33; p = 0.013) and density of Mallory-Denk bodies (MD) (mean 2.27 ± 0.79 versus. 1.69 ± 0.97; p = 0.028) on liver histology. A score derived using BD and MD (range 0-8) had high sensitivity (81%), specificity (64%), and negative predictive value (91%) in identifying patients who did not respond to steroids. The AUROC for a combined MD and BD score of > 5 for predicting steroid non-response was 0.731. Baseline histological parameters in SAH, ballooning degeneration, and Mallory-Denk bodies can reliably identify non-response to corticosteroids and help to stratify patients prior to introduction of therapy.
基线临床和生化参数无法预测重症酒精性肝炎患者对类固醇的无应答。肝活检特征尚未充分评估用于预测重症酒精性肝炎的类固醇治疗反应。我们旨在确定组织学参数，可以预测重症酒精性肝炎（SAH）的类固醇反应。我们分析了 107 例 SAH 患者（71 例在衍生队列中，36 例在验证队列中）的组织学数据，这些患者在黄疸发作后 4 周内出现，并前瞻性接受类固醇（40mg/天）治疗。在衍生队列的治疗前活检中对组织病理学参数进行半定量评分，并开发了一种 SAH 组织学评分系统，该系统可区分类固醇应答者（第 7 天 Lille 评分<0.45）和非应答者。在衍生队列中，71 例患者中有 17 例（24%）和验证队列中有 36 例患者中有 9 例（25%）对类固醇无应答。与应答者相比，无应答者的气球样变性（BD）严重程度更高（平均值 3.87±0.91 与 2.92±1.33；p=0.013）和 Mallory-Denk 体（MD）密度更高（平均值 2.27±0.79 与 1.69±0.97；p=0.028）在肝组织学上。使用 BD 和 MD 得出的评分（范围 0-8）在识别未对类固醇无应答的患者方面具有高敏感性（81%）、特异性（64%）和阴性预测值（91%）。用于预测类固醇无应答的 MD 和 BD 评分之和>5 的 AUROC 为 0.731。SAH、气球样变性和 Mallory-Denk 体的基线组织学参数可可靠地识别对皮质类固醇的无应答，并有助于在引入治疗之前对患者进行分层。
