Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN.
Department of Pathology, Indiana University School of Medicine, Indianapolis, IN.
Hepatology. 2020 Feb;71(2):495-509. doi: 10.1002/hep.30368. Epub 2019 Mar 6.
Vitamin E improves liver histology in adults with nonalcoholic steatohepatitis (NASH) but not diabetes, but its impact on long-term patient outcomes is unknown. We evaluated whether vitamin E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis. Two hundred and thirty-six patients with biopsy-proven NASH and bridging fibrosis or cirrhosis seen at Indiana University Medical Center between October 2004 and January 2016 were included. Ninety of them took 800 international units/day of vitamin E for ≥2 years (vitamin E users) and were propensity-matched to 90 adults who did not take vitamin E (controls) after adjusting for fibrosis severity, age, gender, body mass index, comorbidities and their treatment, low-density lipoprotein cholesterol, liver biochemistries, and length of follow-up on vitamin E. Covariate-adjusted Cox and competing risk regression models were assessed to evaluate the association between vitamin E treatment and patient outcomes. The median follow-up was 5.62 (interquartile range [IQR], 4.3-7.5) and 5.6 (IQR, 4-6.9) years for vitamin E users and controls, respectively. Vitamin E users had higher adjusted transplant-free survival (78% versus 49%, P < 0.01) and lower rates of hepatic decompensation (37% versus 62%, P = 0.04) than controls. After controlling for severity of fibrosis, calendar year of patient enrollment, and other potential confounders, vitamin E treatment decreased the risk of death or transplant (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.12-0.74; P < 0.01) and hepatic decompensation (adjusted sub-HR, 0.52; 95% CI, 0.28-0.96; P = 0.036). These benefits were evident in both those with diabetes and those without diabetes. Adjusted 10-year cumulative probabilities of hepatocellular carcinoma, vascular events, and nonhepatic cancers were not different between vitamin E-exposed patients and controls. Conclusion: Vitamin E use was associated with improved clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis.
维生素 E 可改善非酒精性脂肪性肝炎(NASH)合并桥接纤维化或肝硬化成人的肝脏组织学,但尚不清楚其对长期患者结局的影响。我们评估了维生素 E 治疗是否可改善 NASH 合并桥接纤维化或肝硬化患者的临床结局。纳入了 2004 年 10 月至 2016 年 1 月在印第安纳大学医学中心就诊的经活检证实的 NASH 合并桥接纤维化或肝硬化患者 236 例。其中 90 例患者服用 800 国际单位/天的维生素 E 治疗 ≥2 年(维生素 E 使用者),并在调整纤维化严重程度、年龄、性别、体重指数、合并症及其治疗、低密度脂蛋白胆固醇、肝脏生化指标和维生素 E 随访时间后,与 90 例未服用维生素 E 的成人(对照组)进行倾向评分匹配。采用协变量调整的 Cox 风险和竞争风险回归模型评估维生素 E 治疗与患者结局之间的关系。维生素 E 使用者和对照组的中位随访时间分别为 5.62(四分位距 [IQR],4.3-7.5)和 5.6(IQR,4-6.9)年。维生素 E 使用者的无移植生存率(78%比 49%,P < 0.01)更高,肝失代偿发生率(37%比 62%,P = 0.04)更低。在校正纤维化严重程度、患者入组年份和其他潜在混杂因素后,维生素 E 治疗降低了死亡或移植的风险(调整后的危害比,0.30;95%可信区间 [CI],0.12-0.74;P < 0.01)和肝失代偿的风险(调整后的亚危害比,0.52;95%CI,0.28-0.96;P = 0.036)。这些益处在有糖尿病和无糖尿病的患者中均存在。维生素 E 暴露患者和对照组的 10 年累积肝细胞癌、血管事件和非肝脏癌症发生率无差异。结论:维生素 E 可改善 NASH 合并桥接纤维化或肝硬化患者的临床结局。