Plasma transforming growth factor-β1 level and efficacy of α-tocopherol in patients with non-alcoholic steatohepatitis:: a pilot study

Plasma transforming growth factor-β1 level and efficacy of α-tocopherol in patients with non-alcoholic steatohepatitis:: a pilot study
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DOI:
10.1046/j.1365-2036.2001.01083.x
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发表时间:
2001-10-01
影响因子:
7.6
通讯作者:
Terano, A
Terano, A
中科院分区:
医学1区
文献类型:
--
作者:
Hasegawa, T;Yoneda, M;Terano, A

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背景:非酒精性脂肪性肝炎是一种独特的实体,其特征是脂肪改变、小叶炎症和肝脏纤维化。部分非酒精性脂肪性肝炎进展为肝硬化,但通过无创检查将该病与非酒精性脂肪肝鉴别并不容易。目前还没有经过证实的非酒精性脂肪性肝炎治疗方法。转化生长因子-β1 与肝纤维化的发展有关,并被肝脏中的 α-生育酚(维生素 E)抑制。因此,本研究探讨血浆转化生长因子-β1水平测定的意义以及α-生育酚对非酒精性脂肪性肝炎临床病程的影响。方法:对经肝活检确诊的12例非酒精性脂肪性肝炎患者和10例非酒精性脂肪肝患者进行研究。所有患者均无酗酒史、惯用药物或恶性或炎症性疾病史。所有患者的乙型、丙型和庚型肝炎病毒均为阴性。患者接受为期 6 个月的饮食指导,然后给予 α-生育酚(300 毫克/天)1 年。在 1 年 α-生育酚治疗之前和之后进行血液化学、血浆转化生长因子-β1 水平测量和肝活检。 结果:饮食治疗 6 个月后,非酒精性脂肪肝患者的血清丙氨酸转氨酶水平下降,但非酒精性脂肪性肝炎患者的血清丙氨酸转氨酶水平没有下降。尽管1年α-生育酚治疗期间非酒精性脂肪性肝炎患者的血清丙氨酸转氨酶水平有所降低,但α-生育酚对非酒精性脂肪肝患者的血清丙氨酸转氨酶水平没有影响。非酒精性脂肪性肝炎患者经α-生育酚治疗后,脂肪变性、炎症和纤维化等组织学表现得到改善。与非酒精性脂肪肝患者和健康对照组相比,非酒精性脂肪性肝炎患者血浆转化生长因子-β1水平显着升高,并随着α-生育酚治疗而降低,并伴有血清丙氨酸转氨酶水平改善。结论:我们的数据表明,血浆转化生长因子-β1水平的测量是区分非酒精性脂肪性肝炎和非酒精性脂肪肝的一种可能方法。长期α-生育酚治疗对于非酒精性脂肪性肝炎可能是安全有效的。需要进行随机、对照、双盲试验来确认 α-生育酚在治疗非酒精性脂肪性肝炎方面的全部潜力。
Background: Non-alcoholic steatohepatitis is a distinct entity, characterized by fatty change, lobular inflammation and fibrosis of the liver. Some cases of non-alcoholic steatohepatitis progress to cirrhosis, but it is not easy to distinguish this disease from non-alcoholic fatty liver by non-invasive examinations. No proven therapy for nonalcoholic steatohepatitis exists. Transforming growth factor-beta1 is implicated in the development of liver fibrosis, and is inhibited by alpha -tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor-beta1 and the effect of a-tocopherol on the clinical course of non-alcoholic steatohepatitis were investigated.Methods: Twelve patients with non-alcoholic steatohepatitis and 10 patients with non-alcoholic fatty liver, with a diagnosis confirmed by liver biopsy, were studied. None of the patients had a history of alcohol abuse, habitual medicine or malignant or inflammatory diseases. All patients were negative for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then alpha -tocopherot (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor-beta1 level and liver biopsies were undertaken before and after the 1-year alpha -tocopherol treatment.Results: The serum alanine transaminase level decreased in non-alcoholic fatty liver patients, but not in non-alcoholic steatohepatitis patients, after 6 months of dietary therapy. Although the serum alanine transaminase level in non-alcoholic steatohepatitis patients was reduced during the 1-year alpha -tocopherol treatment, a-tocopherol had no effect on the serum alanine transaminase level in non-alcoholic fatty liver patients. The histological findings, such as steatosis, inflammation and fibrosis, of the non-alcoholic steatohepatitis patients were improved after alpha -tocopherol treatment. The plasma transforming growth factor-beta1 level in non-alcoholic steatohepatitis patients was significantly elevated compared with that in non-alcoholic fatty liver patients and healthy controls, and decreased, accompanied by an improvement in serum alanine transaminase level, with alpha -tocopherol treatment.Conclusions: Our data suggest that the measurement of the level of plasma transforming growth factor-beta1 represents a possible method of distinguishing between non-alcoholic steatohepatitis and non-alcoholic fatty liver. Long-term alpha -tocopherol treatment may be safe and effective for non-alcoholic steatohepatitis. A randomized, controlled, double-blind trial is needed to confirm the full potential of alpha -tocopherol in the management of non-alcoholic steatohepatitis.