Gastroenterology and Hepatology, Specialities Department, University Hospitals of Geneva, 4, Rue Gabrielle Perret-Gentil, CH-1211 Geneva, Switzerland.
BMC Gastroenterol. 2011 Oct 28;11:115. doi: 10.1186/1471-230X-11-115.
BACKGROUND: Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear. METHODS: We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model. RESULTS: 43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001). CONCLUSIONS: In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.
背景：酒精性脂肪性肝炎（ASH）是酒精性肝病的严重并发症。ASH 的诊断需要脂肪变性、肝细胞损伤伴有气球样变性和多核中性粒细胞浸润的肝活检证据。除了肝组织标本中观察到的其他组织学特征外，这些病变是否具有预后意义尚不清楚。
方法：我们研究了 163 名（年龄 55 岁[35-78]，男性/女性 102/61）近期大量（> 80 克/天）饮酒、组织学证实的 ASH（97%伴有潜在肝硬化，Maddrey 评分 39[13-200]，无败血症）患者，这些患者在因临床失代偿住院后 3 天[0-10]进行肝活检。两名病理学家对脂肪变性、肝细胞损伤、中性粒细胞浸润、门管区小管反应、肝内胆汁淤积和铁沉积进行了半定量评估。所有 Maddrey 评分≥32 的患者均接受类固醇治疗。在 3 个月时确定了结局。使用 Wilcoxon 和 Fisher 确切检验、Kaplan-Meier 方法和 Cox 比例风险模型进行统计分析。
结果：活检后 31 天[5-85]内 43 名患者死亡。3 个月的生存率为 74%。两名病理学家的组织学评估的平均 Kappa 值为优秀（0.92）。单因素分析确定年龄、Maddrey 评分、Pugh 评分、MELD 评分和实质内胆汁淤积，但不是其他组织学特征与 3 个月死亡率相关。多因素分析显示，年龄（p = 0.029，OR 2.83[1.11-7.2]）、实质内胆汁淤积（p = 0.001，OR 3.9[1.96-7.8]）和 Maddrey 评分（p = 0.027，OR 3.93[1.17-13.23]）是预后的独立预测因素。与幸存者相比，非幸存者中实质内胆汁淤积更为常见（70%比 25%，p < 0.001）。与无或轻度实质内胆汁淤积相比，严重患者的血清胆红素更高（238[27-636]比 69[22-640]μmol/L，p < 0.001）。
结论：在这一大群入院后早期组织学证实的 ASH 且无败血症的患者中，肝活检发现明显的肝内胆汁淤积是与年龄和 Maddrey 评分一起预测短期不良预后的独立预测因素。可以假设将这个特定的变量纳入现有的 ASH 疾病严重程度评分中会提高其性能。
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