聚乙二醇干扰素α-2α联合利巴韦林累积剂量对失代偿期丙型肝炎肝硬化的疗效

Efficacy of cumulative dose of polyethylene glycol-interferon α-2α combined with ribavirin in patients with decompensatcd hepatitis C virus-related liver cirrhosis

目的观察聚乙二醇干扰素（Peg—IFN）α-2α联合利巴韦林累积剂量对失代偿期丙型肝炎肝硬化患者的疗效，评价抗病毒治疗对疾病进展的影响。方法纳入2005年1月至2009年3月的失代偿期丙型肝炎肝硬化患者，对血细胞达到IFN治疗标准的患者（包括行脾动脉栓塞术的患者）予Peg—IFNα-2α联合利巴韦林治疗，一治疗中根据耐受情况调整Peg—IFNα-2α和利巴韦林的用量，治疗结束后随访24周；将血细胞未达到治疗标准或不愿进行抗病毒治疗的患者作为对照组，随访96周。以累积药物暴露剂量来计算应用药物的总量。观察病毒持续应答率（SVR）、复发率、肝功能和疾病进展状况。组间比较采用t检验或卡方检验，疾病进展率比较采用Kaplan—Meier曲线。结果抗病毒治疗结束后，Peg—IFNα-2α和利巴韦林累积剂量≥60％者，SVR分别为27．3％（12／44）和27．7％（13／47），复发率分别为7／19和35．0％（7／20）；累积剂量〈60%者，SVR分别为1／7和1／4，复发率均为1／2；不同累积剂量比较差异均无统计学意义（P均〉0．05）。联合治疗组在治疗结束后随访24周时的Chil-Pugh评分为（7．9±1．4）分，低于治疗前的（8．5±1．2）分，差异有统计学意义（t=2．33，P=0．02）；对照组在随访96周时的Child-Pugh评分为（10．0±1．6）分，高于治疗前的（8．5±1．4）分，差异有统计学意义（t=5．82，P〈0．01）。联合治疗组的总体疾病进展率为15．7％，低于对照组的32．4％，差异有统计学意义（χ^2=4．34，P=0．04）。结论采用非标准剂量Peg—IFNα-2α联合利巴韦林抗病毒治疗失代偿期丙型肝炎肝硬化患者，只要累积剂量达到一定标准，就可获得病毒学应答，改善患者的Child—Pugh评分，延缓疾病进展。

Objective To observe the efficacy of cumulative dose of polyethylene glycol-interferon （Peg-IFN）α-2α combined with ribavirin in patients with decompensated hepatitis C virus （HCV）-related liver cirrhosis, and to evaluate the effects of anti-virus therapy on the progress of the disease. Methods From January 2005 to March 2009, patients with decompensated HCV-related liver cirrhosis were enrolled, also included patients received partial splenic embolization. Peg-IFNα-2α combined with ribavirin therapy was given to patients whose blood cell met interferon （IFN） therapy standards. The dosage of Peg-IFNα-2α and rihavirin was adjusted according to the tolerance of the patients. After the treatment, the patients were followed-up for 24 weeks. The patients whose blood cell did not meet IFN therapy standards and the patients unwilling to receive anti-virus therapy were assigned to control group and were followed-up for 96 weeks. The total amount of medication was calculated according to cumulative exposure dose. Sustained virological response （SVR）, recurrence rate, liver function and disease progression were observed. The t test or Chi-square test was performed for comparison between groups and rate of disease progression was analyzed with Kaplan Meier curve. Results After anti-virus therapy, SVRs of patients with cumulative dose of Peg IFNα-2α and ribavirin over 60%（include 60 % ） were 27.3% （ 12/44） and 27.7 % （ 13/47）, respectively; the recurrence rates were 7/19 and 35.0 % （7/20）, respectively. In patients with cumulative dose less than 60 %, SVRs were 1/7 and 1/4, respectively, and the recurrence rates were both 1/2; the differences of different doses was not statistically significant （all P〉0.05）. At the 24th week of follow-up after therapy, the Child-Pugh score of combined therapy group was 7.9 ±1.4, which was lower than that before treatment （8.5 ± 1.2）, and the difference was statistically significant （t=2.33,P=0.02）. At the 96th week of follow-up, the Child-Pugh score of control group was 10.0±1.6, which was higher than that before treatment （8. 5 ± 1. 4）, and the difference was statistically significant （t=5.82, P〈0. 01）. The disease progression rate of combined therapy group was 15.7 %, which was lower than that of control group （32.4 % ） , and the difference was statistically significant （χ^2 = 4.34, P = 0. 04）. Conclusion The application of non-standard dosage of Peg-IFNα-2α combined with ribavirin in the patients with decompensated HCV-related liver cirrhosis can achieve virological response once the cumulative dose reached certain standards, improve Child-Pugh scores of patients and slow disease progression.