Oliveira Claudia P, Cotrim Helma P, Stefano Jose Tadeu, Siqueira Ana Cristina G, Salgado Ana Lucia Azevedo, Parise Edison Roberto
Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, Brasil.
Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Departamento de Gastroenterologia e Hepatologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Arq Gastroenterol. 2019 Aug 13;56(2):184-190. doi: 10.1590/S0004-2803.201900000-36.
Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis.
To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH).
Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks.
A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups.
This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.
如今，非酒精性脂肪性肝病（NAFLD）的药物治疗仍然有限，且基于对相关合并症的治疗。氧化应激和胰岛素抵抗似乎是其发病机制中最主要涉及的机制。
评估N - 乙酰半胱氨酸（NAC）联合二甲双胍（MTF）和/或熊去氧胆酸（UDCA）治疗非酒精性脂肪性肝炎（NASH）的疗效。
进行了一项为期48周的开放标签多中心随机试验。纳入经活检证实为NASH的患者。患者被随机分为三组：NAC（1.2 g）+ UDCA（15 mg/kg）+ MTF（850 - 1500 mg/天）（n = 26）；UDCA（20 mg/kg）+ MTF（850 - 1500 mg/天）（n = 13）；NAC（1.2 g）+ MTF（850 - 1500 mg/天）（n = 14），治疗48周。48周后进行临床、实验室检查及第二次肝脏活检。
共评估了53例患者；17例（32.1%）为男性；中位年龄±54（四分位间距 = 15，21 - 71）岁。在基线时，根据临床和组织学参数，各组之间未见差异。各组仅在胆固醇、低密度脂蛋白和甘油三酯方面存在差异。治疗48周后，这三组之间在生化和组织学参数方面未发现显著差异。在比较组织学和生化特征的组内分析（意向性治疗）中，脂肪变性程度（P = 0.014）、气球样变（0.027）以及因此非酒精性脂肪性肝病活动评分（NAS）（P = 0.005）均有显著改善，且仅在NAC + MTF组治疗结束时谷丙转氨酶（ALT）水平有显著改善。在任何一组中均未观察到肝纤维化有明显改变的显著证据。
这项多中心研究表明，NAC + MTF联合应用可降低NASH患者的肝脏疾病活动度。这些数据促使对这些患者采用这种疗法进行进一步的对照研究。
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