Diabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
J Hepatol. 2013 Jul;59(1):131-7. doi: 10.1016/j.jhep.2013.02.007. Epub 2013 Feb 21.
BACKGROUND & AIMS: Lipodystrophies are hypoleptinemic conditions characterized by fat loss, severe insulin resistance, hypertriglyceridemia, and ectopic fat accumulation. Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are also features of this condition. We studied the spectrum of liver disease in lipodystrophy and the effects of leptin replacement.
This was an open-label, prospective study of leptin therapy in patients with inherited and acquired lipodystrophy at the National Institutes of Health. Liver biopsies were performed at baseline (N=50) and after leptin replacement (N=27). NASH activity was assessed using the NASH Clinical Research Network (CRN) scoring system. Fasting blood glucose, triglyceride, hemoglobin A1c and liver enzymes were measured at baseline and at the time of the final liver biopsy.
In leptin-treated patients, 86% met criteria for NASH at baseline, while only 33% had NASH after leptin replacement for 25.8 ± 3.7 months (mean ± SE, p=0.0003). There were significant improvements in steatosis grade (reduction of mean score from 1.8 to 0.9) and ballooning injury scores (from 1.2 to 0.4), with a 44.2% reduction in mean NAFLD activity score (p<0.0001). Patients who already had fibrosis remained stable on leptin replacement. We observed significant improvement in metabolic profile, ALT and AST. In addition to NASH, four patients with acquired generalized lipodystrophy (AGL) had autoimmune hepatitis.
The fundamental liver disease of lipodystrophy is NASH, although autoimmune hepatitis was observed in some patients with AGL. Leptin appears to be a highly effective therapy for NASH in hypoleptinemic lipodystrophic patients.
脂肪营养不良是一种低脂血症的病症，其特征为脂肪丢失、严重胰岛素抵抗、高甘油三酯血症和异位脂肪堆积。非酒精性脂肪性肝病（NAFLD）和脂肪性肝炎（NASH）也是这种病症的特征。我们研究了脂肪营养不良患者的肝病谱以及瘦素替代治疗的效果。
这是一项在国立卫生研究院进行的、针对遗传性和获得性脂肪营养不良患者的瘦素治疗的开放性、前瞻性研究。在基线时（N=50）和接受瘦素替代治疗后（N=27）进行肝活检。采用 NASH 临床研究网络（CRN）评分系统评估 NASH 活动。在基线和最后一次肝活检时测量空腹血糖、甘油三酯、糖化血红蛋白 A1c 和肝酶。
在接受瘦素治疗的患者中，86%在基线时符合 NASH 标准，而在接受瘦素治疗 25.8±3.7 个月后，只有 33%的患者符合 NASH（p=0.0003）。脂肪变性程度评分（从平均 1.8 分降至 0.9 分）和气球样变损伤评分（从 1.2 分降至 0.4 分）有显著改善，NAFLD 活动评分的平均下降率为 44.2%（p<0.0001）。已经有纤维化的患者在接受瘦素替代治疗时仍保持稳定。我们观察到代谢特征、ALT 和 AST 有显著改善。除了 NASH，4 例获得性全身性脂肪营养不良（AGL）患者还患有自身免疫性肝炎。
脂肪营养不良的基本肝病是 NASH，尽管一些 AGL 患者还观察到自身免疫性肝炎。瘦素似乎是治疗低脂血症性脂肪营养不良患者 NASH 的一种非常有效的治疗方法。
