Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India.
Eur J Gastroenterol Hepatol. 2011 Mar;23(3):210-7. doi: 10.1097/MEG.0b013e3283435d76.
Pentoxifylline is effective in prevention of hepatorenal syndrome (HRS) in alcoholic hepatitis. The aim of this study was to assess the efficacy of pentoxifylline for prophylaxis of HRS in patients with cirrhosis and ascites.
One hundred and seventy-six consecutive patients with cirrhosis and ascites were screened. Patients with creatinine clearance (Ccl) between 41 and 80 ml/min and serum creatinine of less than 1.5 mg/dl in absence of renal disease were randomized to receive either pentoxifylline (group A, 1200 mg/day) or placebo (group B) for 6 months. Patients were followed monthly for 6 months, and kidney function tests were carried out at baseline, 1, 3, and 6 months. Primary endpoint was the development of HRS within 6-month follow-up.
Thirty-five patients each were randomized to group A and group B. Of the 70 patients, 61 completed follow-up (group A, n = 30 and group B, n = 31). In group A, serum creatinine remained stable at 1 month (0.94±0.2 vs. 0.90±0.4 mg/dl, P = 0.43), at 3 months (0.94±0.2 vs. 0.80±0.3 mg/dl, P = 0.10), and at 6 months (0.94±0.2 vs. 0.8±0.2 mg/dl, P = 0.06). Improvement occurred in Ccl at 1 month (61.7±16.0 vs. 82.0±30.0 ml/min, P = 0.001) and at 3 months (61.7±16.0 vs. 86.2±30.7 ml/min, P = 0.001). Serum sodium in group A showed progressive improvement at 1 month (134.7±4.4 vs. 137.0±5.3 mmol/l, P = 0.006), at 3 months (134.7±4.4 vs. 138.4±5.4 mmol/l, P = 0.004), and at 6 months (134.7±4.4 vs. 137.6±4.9 mmol/l, P = 0.009). Similarly, mean arterial pressure (MAP) also showed progressive improvement at 1 month (76.7±6.7 vs. 81.8±6.9 mmHg, P = 0.001), at 3 months (76.7±6.7 vs.82.3±6.2 mmHg, P = 0.001), and at 6 months (76.7±6.7 vs. 82.6±6.1 mmHg, P = 0.01). Tumor necrosis factor (TNF) level measured at baseline and at 3 months (14.4±4.8 vs. 13.1±3.7 pg/ml, P = 0.28) showed no difference in group A patients. In group B, serum creatinine increased gradually at 1 month (0.80±0.2 vs. 1.0±0.2 mg/dl, P = 0.007), at 3 months (0.80±0.2 vs. 1.1±0.3 mg/dl, P = 0.001), and at 6 months (0.80±0.2 vs.1.1±0.2 mg/dl, P = 0.001). Ccl at 1 month (63.1±14.5 vs. 66.8±28.2 ml/min, P = 0.37) decreased at 3 months (63.1±14.5 vs. 54.4±18.3 ml/min, P = 0.008). Serum sodium, in group B, showed progressive decline at 1 month (136.2±5.0 vs. 132.7±3.2 mmol/l, P = 0.02) and at 6 months (136.2±5.0 vs. 132.7±3.4 mmol/l, P = 0.002). MAP remained stable at 1 month (75.1±7.5 vs. 75.3.8±5.1 mmHg, P = 0.86), at 3 months (75.1±7.5 vs. 73.2±4.6 mmHg, P = 0.19), and at 6 months (75.1±7.5 vs. 74.1±6.1 mmHg, P = 0.06). TNF level also did not show any change at baseline and at 3 months (14.5±6.8 vs. 13.4±5.1 pg/ml, P = 0.31). Of the 12 patients who developed HRS, 10 patients were in group B (type 1 HRS, n = 9 and type 2 HRS, n = 1) and two patients (type-1 HRS, n = 2) were in group A (P = 0.01). Patients with HRS had higher baseline TNF-α (15.3±5.8 vs. 10.9±4.8 pg/ml, P = 0.01), lower MAP (68.0±3.8 vs. 77.8±6.5 mmHg, P = 0.01), and sodium level (131.2±3.0 vs. 135.6±4.7 mmol/l, P = 0.003) than those who did not develop HRS.
Pentoxifylline is effective in preventing HRS in patients with cirrhosis and ascites at risk of HRS.
己酮可可碱可有效预防酒精性肝炎患者的肝肾综合征（HRS）。本研究旨在评估己酮可可碱预防肝硬化伴腹水患者发生 HRS 的疗效。
对 176 例连续肝硬化伴腹水患者进行筛选。肌酐清除率（Ccl）在 41-80ml/min 之间且血清肌酐＜1.5mg/dl 且无肾脏疾病的患者随机分为两组，分别接受己酮可可碱（1200mg/天，A 组）或安慰剂（B 组）治疗 6 个月。两组患者均每月随访 6 个月，并在基线、1、3 和 6 个月时进行肾功能检查。主要终点是在 6 个月的随访中是否发生 HRS。
每组 35 例患者随机分组。70 例患者中，61 例完成了随访（A 组 30 例，B 组 31 例）。A 组患者在 1 个月时血清肌酐保持稳定（0.94±0.2 与 0.90±0.4mg/dl，P=0.43），3 个月时（0.94±0.2 与 0.80±0.3mg/dl，P=0.10），6 个月时（0.94±0.2 与 0.8±0.2mg/dl，P=0.06）。1 个月时 Ccl 改善（61.7±16.0 与 82.0±30.0ml/min，P=0.001），3 个月时（61.7±16.0 与 86.2±30.7ml/min，P=0.001）。A 组患者血清钠水平逐渐改善，1 个月时（134.7±4.4 与 137.0±5.3mmol/l，P=0.006），3 个月时（134.7±4.4 与 138.4±5.4mmol/l，P=0.004），6 个月时（134.7±4.4 与 137.6±4.9mmol/l，P=0.009）。同样，平均动脉压（MAP）也逐渐改善，1 个月时（76.7±6.7 与 81.8±6.9mmHg，P=0.001），3 个月时（76.7±6.7 与 82.3±6.2mmHg，P=0.001），6 个月时（76.7±6.7 与 82.6±6.1mmHg，P=0.01）。A 组患者在基线和 3 个月时的肿瘤坏死因子（TNF）水平（14.4±4.8 与 13.1±3.7pg/ml，P=0.28）无差异。B 组患者在 1 个月时血清肌酐逐渐升高（0.80±0.2 与 1.0±0.2mg/dl，P=0.007），3 个月时（0.80±0.2 与 1.1±0.3mg/dl，P=0.001），6 个月时（0.80±0.2 与 1.1±0.2mg/dl，P=0.001）。1 个月时 Ccl 下降（63.1±14.5 与 66.8±28.2ml/min，P=0.37），3 个月时（63.1±14.5 与 54.4±18.3ml/min，P=0.008）。B 组患者血清钠水平逐渐下降，1 个月时（136.2±5.0 与 132.7±3.2mmol/l，P=0.02），6 个月时（136.2±5.0 与 132.7±3.4mmol/l，P=0.002）。1 个月时 MAP 保持稳定（75.1±7.5 与 75.3.8±5.1mmHg，P=0.86），3 个月时（75.1±7.5 与 73.2±4.6mmHg，P=0.19），6 个月时（75.1±7.5 与 74.1±6.1mmHg，P=0.06）。TNF 水平在基线和 3 个月时也没有变化（14.5±6.8 与 13.4±5.1pg/ml，P=0.31）。发生 HRS 的 12 例患者中，10 例（1 型 HRS9 例，2 型 HRS1 例）在 B 组，2 例（1 型 HRS2 例）在 A 组（P=0.01）。发生 HRS 的患者 TNF-α水平较高（15.3±5.8 与 10.9±4.8pg/ml，P=0.01），MAP 较低（68.0±3.8 与 77.8±6.5mmHg，P=0.01），钠水平较低（131.2±3.0 与 135.6±4.7mmol/l，P=0.003）。
己酮可可碱可有效预防肝硬化伴腹水且有发生肝肾综合征风险的患者发生 HRS。
