Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease.
Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease.
复制标题
DOI：
10.1053/j.gastro.2015.04.043
复制
发表时间：
2015-08
期刊：
影响因子：
29.4
通讯作者：
Bendtsen F
中科院分区：
文献类型：
--
作者：
Angulo P;Kleiner DE;Dam-Larsen S;Adams LA;Bjornsson ES;Charatcharoenwitthaya P;Mills PR;Keach JC;Lafferty HD;Stahler A;Haflidadottir S;Bendtsen F
肝活检的组织学分析允许对非酒精性脂肪性肝病（NAFLD）进行分级和分期。我们进行了一项纵向研究，以调查NAFLD患者组织学特征的长期预后相关性。我们对1975年至2005年在美国、欧洲和泰国的医疗中心诊断为NAFLD的619例患者进行了回顾性分析。患者接受实验室和活检分析，并在诊断后每3-12个月进行一次检查。分析的结局包括总死亡率、肝移植和肝脏相关事件。通过对数秩分析比较累积结局。使用考克斯比例风险回归估计校正的风险比（HR）。风险时间确定为从肝活检日期至结局日期或末次随访检查日期。中位随访时间为12.6年（范围0.3-35.1年），193例患者（33.2%）死亡或接受肝移植。与死亡或肝移植显著相关的肝活检特征包括纤维化1期（HR，1.88; 95% CI，1.28，2.77），2期（HR，2.89; 95% CI，1.93，4.33），3期（HR，3.76; 95% CI，2.40，5.89）和4期（HR，10.9; 95% CI，6.06，19.62）与0期相比，以及年龄（HR，1.07; 95% CI，1.05，1.08），糖尿病（HR，1.61; 95% CI，1.13，2.30）、当前吸烟（HR，2.62; 95% CI，1.67，4.10）和他汀类药物使用（HR，0.32; 95% CI，0.14，0.70）。26例患者（4.2%）发生肝脏相关事件;与0期相比，3期纤维化（HR 14.2 [95% CI 3.38，59.68]）和4期纤维化（HR 51.5 [95% CI 9.87，269.2]）与事件显著相关。无论脂肪性肝炎或NAFLD活动性评分如何，纤维化患者的生存时间均短于无纤维化患者。在一项NAFLD患者的纵向研究中，纤维化分期与长期总死亡率、肝移植和肝脏相关事件独立相关，但没有脂肪性肝炎的其他组织学特征。
Histologic analysis of liver biopsies allows for grading and staging of nonalcoholic fatty liver disease (NAFLD). We performed a longitudinal study to investigate the long-term prognostic relevance of histologic features for patients with NAFLD. We performed a retrospective analysis of 619 patients diagnosed with NAFLD from 1975 through 2005 at medical centers in the United States, Europe, and Thailand. Patients underwent laboratory and biopsy analyses, and were examined every 3–12 months after their diagnosis. Outcomes analyzed were overall mortality, liver transplantation, and liver-related events. Cumulative outcomes were compared by log-rank analysis. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (HR). Time at risk was determined from the date of liver biopsy to the date of outcome or last follow-up examination. Over a median follow-up of 12.6 years (range 0.3–35.1), 193 of the patients (33.2%) died or underwent liver transplantation. Features of liver biopsies significantly associated with death or liver transplantation included fibrosis stage 1 (HR, 1.88; 95% CI, 1.28, 2.77), stage 2 (HR, 2.89; 95% CI, 1.93, 4.33), stage 3 (HR, 3.76; 95% CI, 2.40, 5.89), and stage 4 (HR, 10.9; 95% CI, 6.06, 19.62) compared with stage 0, as well as age (HR, 1.07; 95% CI, 1.05, 1.08), diabetes (HR, 1.61; 95% CI, 1.13, 2.30), current smoking (HR, 2.62; 95% CI, 1.67, 4.10) and statin use (HR, 0.32; 95% CI, 0.14, 0.70). Twenty-six patients (4.2%) developed liver-related events; fibrosis stage 3 (HR 14.2 [95% CI 3.38, 59.68]) and stage 4 (HR 51.5 [95% CI 9.87, 269.2]) compared to stage 0, were significantly associated with the events. Patients with fibrosis, regardless of steatohepatitis or NAFLD activity score, had shorter survival times than patients without fibrosis. In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were independently associated with long-term overall mortality, liver transplantation, and liver-related events.