非酒精性脂肪性肝病患儿肝组织学异常与丙氨酸氨基转移酶正常或轻度升高。
Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels.
机构信息
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine, Indianapolis, IN.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, CA; Department of Gastroenterology, Rady Children's Hospital, San Diego, CA; Liver Imaging Group, Department of Radiology, University of California, San Diego School of Medicine, La Jolla, CA.
出版信息
J Pediatr. 2014 Apr;164(4):707-713.e3. doi: 10.1016/j.jpeds.2013.10.071. Epub 2013 Dec 19.
OBJECTIVE
To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26-50 U/L boys, 23-44 U/L girls), or elevated (>50 U/L in boys, >44 U/L in girls) serum alanine aminotransferase (ALT) levels.
STUDY DESIGN
The Nonalcoholic Steatohepatitis Clinical Research Network enrolls children aged 5-18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy analysis within 180 days of ALT measurement, and compared them with data from 392 children with elevated ALT.
RESULTS
Seventeen of the 91 children with suspected NAFLD (19%) had a normal ALT level, and 74 (81%) had a mildly elevated ALT level. Overall, 45% of the biopsy specimens analyzed had steatosis ≥33%, 22% had grade ≥2 lobular inflammation, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had "suspicious/borderline" steatohepatitis, 8% had definite nonalcoholic steatohepatitis, 34% had an NAFLD activity score ≥4, and 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in the patients with mildly elevated ALT compared with those with normal ALT, with no difference in ballooning, inflammation, or NAFLD activity score ≥4 between the 2 groups. Fibrosis stage 3/4 was seen in none of the children with normal ALT, in 9% of those with mildly elevated ALT, and in 15% of those with elevated ALT.
CONCLUSION
Liver biopsy specimens from children with NAFLD with normal or mildly elevated ALT levels show significant histological abnormalities, including advanced fibrosis in children with mildly elevated ALT. Thus, measurement of ALT may underestimate liver injury in NAFLD. The use of appropriate ALT cutoff levels can help identify children at risk for more severe disease.
目的
探讨血清丙氨酸氨基转移酶（ALT）水平正常、轻度升高（男孩 26-50U/L，女孩 23-44U/L）或升高（男孩>50U/L，女孩>44U/L）的儿童非酒精性脂肪性肝病（NAFLD）的组织学谱。
研究设计
非酒精性脂肪性肝炎临床研究网络招募了年龄在 5-18 岁的 NAFLD 患儿。我们分析了 91 例疑似 NAFLD 且 ALT 正常或轻度升高的患儿及 ALT 测量后 180 天内进行肝活检分析的基线临床和组织学数据，并与 392 例 ALT 升高的患儿数据进行了比较。
结果
91 例疑似 NAFLD 的患儿中，17 例（19%）ALT 水平正常，74 例（81%）ALT 水平轻度升高。总体而言，分析的活检标本中 45%有≥33%的脂肪变性，22%有≥2 级的小叶炎症，81%有门脉炎症，29%有气球样肝细胞，35%有“可疑/临界”脂肪性肝炎，8%有明确的非酒精性脂肪性肝炎，34%有≥4 的 NAFLD 活动评分，46%有纤维化（38%为轻度/中度，8%为桥接/肝硬化）。与 ALT 正常的患儿相比，ALT 轻度升高的患儿显著更易发生明显的脂肪变性（50% vs. 24%）和纤维化（54% vs. 12%），两组间的气球样变、炎症或≥4 的 NAFLD 活动评分无差异。ALT 正常的患儿中无一例出现纤维化 3/4 期，ALT 轻度升高的患儿中 9%出现纤维化 3/4 期，ALT 升高的患儿中 15%出现纤维化 3/4 期。
结论
ALT 正常或轻度升高的 NAFLD 患儿的肝活检标本显示出显著的组织学异常，包括 ALT 轻度升高的患儿存在进展性纤维化。因此，ALT 的测量可能低估了 NAFLD 患儿的肝损伤。使用适当的 ALT 截断值有助于识别更易发生严重疾病的患儿。
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