Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes
Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes
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DOI：
10.1002/hep.22429
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发表时间：
2008-09-01
期刊：
影响因子：
13.5
通讯作者：
Fargion, Silvia
中科院分区：
文献类型：
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作者：
Fracanzani, Anna Ludovica;Valenti, Luca;Fargion, Silvia
目前还不确定非酒精性脂肪肝（NAFLD）和丙氨酸氨基转移酶（ALT）正常的患者是否有较轻的疾病，并应进行肝活检。我们回顾了458例意大利NAFLD患者的组织学资料，其中肝活检显示肝酶改变（395例，86%），或铁蛋白持续升高或长期严重脂肪变性（63例）。通过多因素分析确定非酒精性脂肪性肝炎（NASH）和纤维化的相关因素. ALT正常的患者年龄明显较大，体重指数、空腹甘油三酯、胰岛素抵抗（根据稳态模型评估（HOMA-IR））、ALT和γ-谷氨酰转移酶较低，但高血压患病率较高。在ALT正常和升高的患者中，NASH的诊断率分别为59%和74%（P = 0.01）。在整个患者系列中，ALT（比值比[OR]，1.11; 95%置信区间[CI]，1.04-1.19/10-IU/mL增加）和糖尿病（OR，1.5; 95% CI，1.1-2.0）独立预测NASH。在ALT升高的患者中选择相同的变量，而在ALT正常的患者中，HOMA-IR和ALT是独立的预测因子。血清铁蛋白是严重纤维化的独立预测因子（OR，1.04; 95% CI，每增加50 ng/mL，1.001-1.08），ALT（OR，1.07; 95% CI，1.02-1.14），和糖尿病（OR，1.8; 95% CI，1.4-2-3）在整个系列中，血清铁蛋白和糖尿病在ALT升高的患者中，仅HOMA-IR ALT正常患者的OR为1.97; 95%CI为1.2-3.7。结论：ALT正常并不是排除肝活检患者的有价值的标准。在选择NAFLD病例进行疾病严重程度和进展的组织学评估时，还应考虑ALT正常受试者的葡萄糖代谢和胰岛素抵抗变化。
It is uncertain whether patients with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) have a milder disease and should undergo liver biopsy. We reviewed the histological data of 458 Italian patients with NAFLD in whom liver biopsy was indicated by altered liver enzymes (395 cases, 86%), or persistently elevated ferritin or long-lasting severe steatosis (63 cases). Factors associated with nonalcoholic steatohepatitis (NASH) and fibrosis it 2 were identified by multivariate analysis. Patients with normal ALT were significantly older, had lower body mass index, fasting triglycerides, insulin resistance according to homeostasis model assessment (HOMA-IR), ALT, and gamma-glutamyltransferase, but a higher prevalence of hypertension. NASH was diagnosed in 59% and 74% of the patients with normal and increased ALT, respectively (P = 0.01). In the overall series of patients, NASH was independently predicted by ALT (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.19 per 10-IU/mL increase) and diabetes (OR, 1.5; 95% CI, 1.1-2.0). The same variables were selected in patients with increased ALT, whereas in those with normal ALT, HOMA-IR and ALT were independent predictors. Severe fibrosis was independently predicted by serum ferritin (OR, 1.04; 95% CI, 1.001-1.08 per 50-ng/mL increase), ALT (OR, 1.07; 95% CI, 1.02-1.14), and diabetes (OR, 1.8; 95% CI, 1.4-2-3) in the overall series, serum ferritin and diabetes in those with increased ALT, and only HOMA-IR (OR, 1.97; 95% CI, 1.2-3.7) in patients with normal ALT. Conclusion: Normal ALT is not a valuable criterion to exclude patients from liver biopsy. Alterations in glucose metabolism and insulin resistance in subjects with normal ALT should also be considered in the selection of NAFLD cases for histological assessment of disease severity and progression.