Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network.
Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network.
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DOI：
10.1002/hep.22724
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发表时间：
2009-03
期刊：
影响因子：
13.5
通讯作者：
Neuschwander-Tetri, Brent A.
中科院分区：
文献类型：
--
作者：
Brunt, Elizabeth M.;Kleiner, David E.;Wilson, Laura A.;Unalp, Aynur;Behling, Cynthia E.;Lavine, Joel F.;Neuschwander-Tetri, Brent A.
未经治疗的成人非酒精性脂肪性肝病（NAFLD）的特征是没有或轻微的门静脉慢性炎症（CI）；在以门静脉为基础的小儿NAFLD中，门静脉CI可能是主要的组成部分。本研究旨在将NASH CRN受试者的临床特征与门脉CI联系起来。对728名成人和205名儿童进行中心分级组织学和与活检时间相关的临床参数评估。60%的成人活组织检查为轻度，23%为轻度以上，16%无门脉CI。在儿童中，76%为轻度，14%为轻度以上，10%为无门脉CI。两组患者均未发现自身抗体、ALT升高或使用“任何”药物与门脉CI的存在或程度相关。成人中与“轻度以上”相关的临床特征为：年龄较大（51岁vs 44岁）（p<0.0001）、女性（p=0.001）、BMI较高（p<0.0001）、胰岛素水平升高（中位数为20 v 14uU/ml） （p=0.001）、HOMA-IR较高（中位数为5 v 3） （p<0.0001）、NAFLD （p=0.0004）、糖尿病（p<0.0001）和高血压（p<0.0001）。小儿活组织检查中“轻度以上”与“无”的相同比较显示，仅与年龄较小（12岁vs 14岁）有关（p=0.01），但有倾向于男孩。与BMI、胰岛素或HOMA-IR无关。在两组中，小叶和门静脉炎症评分没有相关性，但与明确的脂肪性肝炎诊断有相关性（两者的p<0.0001）。成人活检中与“轻度以上”相关的特征是脂肪变性的数量（p=0.01）和部位（p<0.0001）、气球的存在（p<0.0001）和晚期纤维化（p<0.0001）。在儿科活检中，“轻度以上”与“无”相比与脂肪变性部位（p=0.0008）和纤维化评分（p<0.0001）相关，特别是儿科（1区加重）模式（p<0.001）和门脉/门脉周围纤维化（或更晚期纤维化）（p<0.01）。门脉CI升高与成人和儿童进行性NAFLD的许多临床和病理特征相关，但与ALT、自身抗体或小叶炎症无关。未经治疗的NAFLD肝活检中出现轻度以上的门脉CI可能被认为是临床和组织学上疾病进展的标志。
Untreated adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in the portal-based pediatric pattern of NAFLD, portal CI may be a predominant component. This study was undertaken to correlate clinical features with portal CI in the subjects enrolled in the NASH CRN. Histology from central grading and clinical parameters temporally related to the biopsy were evaluated from 728 adults and 205 children. Sixty percent of adult biopsies had mild, 23% had more than mild, and 16% had no portal CI. In children, 76% had mild, 14% were more than mild, and 10% had no portal CI. In neither group were autoantibodies, elevated ALT, or generic use of “any” medications associated with the presence or degree of portal CI. Clinical features associated with “more than mild” in adults were older age (51 y v 44 y) (p<0.0001), female gender (p=0.001), higher BMI (p<0.0001), elevated insulin levels (median 20 v 14uU/ml) (p=0.001), higher HOMA-IR (median 5 v 3) (p<0.0001), and medications used for NAFLD (p=0.0004), diabetes (p<0.0001), and hypertension (p<0.0001). The same comparisons for “more than mild” v “none” in the pediatric biopsies showed only an association with younger age (12 y v 14 y) (p=0.01), but there was a trend favoring boys. There was no association with BMI, insulin or HOMA-IR. In both groups, lobular and portal inflammation scores had no association, but there was an association with a definite steatohepatitis diagnosis (p<0.0001 for both). Features in the adult biopsies associated with “more than mild” were steatosis amount (p=0.01and location (p<0.0001), presence of ballooning (p<0.0001), and advanced fibrosis (p<0.0001). In the pediatric biopsies, “more than mild” compared with “none” was associated with steatosis location (p=0.0008), and fibrosis score (p<0.0001), specifically, the pediatric (zone 1 accentuation) pattern (p<0.001) and portal/periportal fibrosis (or more advanced fibrosis) (p<0.01). Increased portal CI is associated with many clinical and pathologic features of progressive NAFLD in both adults and children, but not with ALT, autoantibodies, or lobular inflammation. The presence of more than mild portal CI in liver biopsies of untreated NAFLD may be considered a marker of clinically and histologically advanced disease.
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影响因子：
13.5
作者：
Caldwell, SH;Oelsner, DH;Driscoll, CJ
通讯作者：
Driscoll, CJ
影响因子：
13.5
作者：
Clouston, AD;Powell, EE;Jonsson, JR
通讯作者：
Jonsson, JR
影响因子：
29.4
作者：
Ratziu, V;Giral, P;Poynard, T
通讯作者：
Poynard, T
影响因子：
3.8
作者：
Kral, JG;Thung, SN;Marceau, P
通讯作者：
Marceau, P
超越胰岛素抵抗：非酒精性脂肪性肝炎的先天免疫力。
影响因子：
13.5
作者：
Maher, Jacquelyn J.;Leon, Pablo;Ryan, James C.
通讯作者：
Ryan, James C.