Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis - A pilot study
Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis - A pilot study
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DOI：
10.1001/jama.282.17.1659
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发表时间：
1999-11-03
影响因子：
120.7
通讯作者：
Diehl, AM
中科院分区：
文献类型：
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作者：
Cortez-Pinto, H;Chatham, J;Diehl, AM
背景推动脂肪肝发展为脂肪性肝炎和肝硬变的机制尚不清楚。在动物模型中，肥胖的脂肪肝小鼠容易发生肝脏三磷酸腺苷(ATP)的耗竭和坏死，提示可能参与了肝脏能量平衡的改变。目的确定脂肪肝病II患者从肝脏ATP耗竭中恢复受损的情况。设计实验室分析核磁共振监测的肝脏ATP储备量在果糖注射诱导短暂的肝脏ATP耗竭前后的变化。该研究于1998年7月15日至8月30日在北京大学附属医院进行。连续8例经活检证实的成人非酒精性脂肪性肝炎患者和7例年龄和性别匹配的健康对照人员。结果两组患者的血清转氨酶水平均升高(P=0.02比对照组)，白蛋白和胆红素水平正常，无门脉高压的临床证据。然而，在肝活检中，2例患者为中度纤维化，1例为肝硬变。两组间平均血糖、胆固醇和甘油三酯水平相似，但患者的体重明显高于对照组(P=0.02)。在注射果糖之前，两组的肝脏ATP水平相似，在注射果糖后，两组的肝脏ATP水平下降相似(P=0.01，与最初的ATP水平相比)。然而，对照组在1小时的随访期内补充了他们的肝脏ATP储备(P
Context The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altered hepatic energy homeostasis may be involved.Objective To determine ii patients with fatty liver disease exhibit impaired recovery from hepatic ATP depletion.Design Laboratory analysis of liver ATP stores monitored by nuclear magnetic resonance spectroscopy before and after transient hepatic ATP depletion was induced by fructose injection. The study was conducted between July 15 and August 30, 1998.Setting University hospital.Patients Eight consecutive adults with biopsy-proven nonalcoholic steatohepatitis and 7 healthy age- and sex-matched controls.Main Outcome Measure Level of ATP 1 hour after fructose infusion in patients vs controls.Results In patients, serum aminotransferase levels were increased (P = .02 vs controls); albumin and bilirubin values were normal and clinical evidence of portal hypertension was absent in both groups. However, 2 patients had moderate fibrosis and 1 had cirrhosis on liver biopsy. Mean serum glucose, cholesterol, and triglyceride levels were similar between groups but patients weighed significantly more than controls (P = .02). Liver ATP levels were similar in the 2 groups before fructose infusion and decreased similarly in both after fructose infusion (P = .01 vs initial ATP levels). However, controls replenished their hepatic ATP stores during the 1-hour follow-up period (P