Ćulafić Milica, Vezmar-Kovačević Sandra, Dopsaj Violeta, Oluić Branislav, Bidžić Nemanja, Miljković Branislava, Ćulafić Đorđe
University of Belgrade, Faculty of Pharmacy, Department of Pharmacokinetics and Clinical Pharmacy.
University of Belgrade, Faculty of Pharmacy, Clinical Centre of Serbia, Department of Medical Biochemistry, Belgrade.
J Med Biochem. 2020 Sep 2;39(3):290-298. doi: 10.2478/jomb-2019-0043.
The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic.
A prospective trial was conducted. The first cohort included patients with biopsy-proven Nash, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in Nash group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications.
All 33 Nash patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 mmol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA - IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase by 24.0 U/L, 9.1 U/L, 10.8 U/L respectively, was noted.
Pentoxifylline and Metformin may provide possible treatment option in Nash. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.
非酒精性脂肪性肝病进展为非酒精性脂肪性肝炎(NASH)是多因素导致的,目前仍缺乏经批准用于治疗该病的药物。本研究旨在评估己酮可可碱与二甲双胍联合治疗对NASH患者生化指标的影响。研究地点:门诊肝病诊所。
进行了一项前瞻性试验。第一组包括经活检证实患有NASH的患者,第二组由经活检确诊为NAFLD的患者组成。在基线时和每三个月进行一次血液检查。己酮可可碱组剂量为400mg,每日三次,二甲双胍组剂量为500mg,每日三次,在NASH组中使用六个月。基于低成本药物联合治疗后的生化结果评估治疗效果。
所有33例NASH患者均完成了24周的治疗。我们观察到治疗后以下参数的中位数有显著改善(p<0.05):血清尿酸水平降低51.0mmol/L,钙降低0.27mmol/L,镁升高0.11mmol/L。检测到胰岛素抵抗改善,HOMA-IR降低了1.3。观察到肝酶、丙氨酸转氨酶、天冬氨酸转氨酶和γ-谷氨酰转移酶的中位数分别显著降低24.0U/L、9.1U/L、10.8U/L。
己酮可可碱和二甲双胍可能为NASH提供一种可行的治疗选择。该疗法在改善肝功能同时降低心血管风险方面有一些新的潜在益处。