慢性丙型肝炎患者停药后复发的影响因素分析

Causes and countermeasures for relapse after drug withdrawal in patients with chronic hepatitis C

目的探讨慢性丙型肝炎（CHC）患者停药复发的原因及影响因素。方法选取2010年4月-2013年3月于兰州市第一人民医院就诊及住院的患者101例,其中男36例,女65例,代偿期肝硬化患者26例,慢性肝炎患者75例,年龄19~71岁,所有患者均为初治患者。治疗前行血常规、生化、自身抗体、甲状腺功能、HCV RNA载量、HCV基因分型等检测。治疗第4、12、24周、治疗结束时、治疗结束后12、24、48、72、96周等时间点进行肝功能、血常规、HCV RNA载量的检测。停药后随访96周,根据是否检测出HCV RNA,分为复发组和未复发组,复发组中又分为24周内复发和获得持续性病毒学应答（SVR）复发两组,观察各组基线水平、4周病毒学应答率、生化学应答率,治疗方案等对复发的影响。计数资料组间比较采用χ2检验,不满足χ2检验条件时采用Fisher检验,计量资料组间比较采用t检验。结果 101例患者中71例患者获得快速病毒学应答（RVR）,占70.3%;90例患者获得早期病毒学应答（EVR）,占89.1%;9例患者无应答或治疗期间HCV RNA反弹,占8.9%。92例患者获得治疗末病毒学应答（ETVR）,占91.1%,其中基因1b型患者28例,占获得ETVR例数的30.4%。非基因1型患者共64例,占获得ETVR例数的69.6%。获得ETVR的92例患者中接受标准化治疗方案60例,占65.2%,接受非标准化治疗方案患者32例,占34.8%。92例患者停药2年随访,30例患者停药复发,占ETVR的32.6%,其中13例停药24周内复发,占复发患者的43.3%。获得SVR后复发17例,占复发患者的56.7%,占SVR的21.5%,占ETVR的18.5%。复发组和未复发组在年龄、病毒载量、有无合并肝硬化、4周ALT复常率、RVR率及非标准化治疗率等方面差异有统计学意义（t值为2.624,χ2值分别为15.199、4.469、7.352、7.453、19.950,P值均〈0.05）。近期复发与获得SVR复发患者比较,在HCV RNA载量、是否采用标准化治疗两方面比较差异有统计学意义（P值均〈0.05）。结论CHC治疗后停药复发的原因与年龄、病毒载量、肝硬化、ALT复常率、RVR率和非标准治疗等因素有关。高病毒载量和非标准化治疗是导致患者近期复发的主要原因。

Objective To study the causes and influential factors for relapse after drug withdrawal in patients with chronic hepatitis C （CHC）. Methods One hundred and one cases of CHC, including 36 males and 65 females, who were outpatients or inpatients in our hospital, were enrolled as subjects. Twenty - six patients had compensated cirrhosis, and seventy - five had chronic hepatitis. Their age ranged from 19 to 71 years. All patients had no treatment history. Routine blood indices, biochemical parameters, autoautibodies, thyroid function, hepatitis C viral load （HCV RNA） , and hepatitis C virus （HCV） genotypes were evaluated before treatment. Liver function, routine blood indices, and HCV RNA load were evaluated at weeks 4, 12, 24, and the end of treatment, as well as 12, 24, 48, 72, and 96 weeks aiier treatment. The follow - up time after drug withdrawal was 96 weeks. All patients were divided into relapse group and sustained response group, according to whether HCV RNA was detected or not. Patients in the relapse group were further divided into two groups： relapse within 24 weeks and relapse after achieving sustained virological response （SVR）. The effects of baseline levels, 4 - week virological response rates, biochemical response rates, and treatment regimen on relapse were assessed. Between - group comparison of categorical data was performed byx2 test, and between - group comparison of continuous data was performed by t test. Results In all patients, 71 patients （ 70. 3% ） had rapid virological response （ RVR）, 90 patients （ 89.1% ） had early virological response, and 9 patients （ 8.9% ） had no response or restored HCV RNA during treatment. Among 92 patients （91.1%） with end - of - treatment virological response （ ETVR）, 28 patients （30.4%） had genotype lb, while 64 patients （69.6%） had non -1 genotypes. Among 92 patients with ETVR, 60 patients （ 65.2% ） received the standard treatment, while 32 patients （34.8%） received the non - standard treatment. During a 2 - year follow - up of 92 patients with ETVR after drug withdrawal, 30 patients （32.6%） had relapse after drug withdrawal, including 13 patients （43.3%） who had relapse within 24 weeks after drug withdrawal, and 17 patients （56.7% of patients with relapse; 21.5% of patients with SVR; 18.5% of patients with ETVR） who had relapse after achieving SVR. There were significant differences in age, HCV RNA load, cirrhosis, 4 - week alanine aminotransferase （ALT） normalization rate, RVR rate, and non - standard treatment rate between the relapse group and the non - relapse group （t=2.624, P〈0.05,x^2 =15.199, P〈0.05;x^2 =4.469, P〈0.05;x^2 =7.352, P〈0.05;x^2 =7.453, P〈 0. 05 ; x^2 = 19. 950, P 〈0.05 ）. The genotype and gender were not influencing factors for relapse. There were significant differences in HCV RNA load, cirrhosis, and standard treatment rate between patients with short - term relapse and relapse after achieving SVR （ P 〈 0.05 ）. Conclusion The causes for relapse after drug withdrawal in patients with CHC involve age, viral load, cirrhosis, ALT normalization rate, RVR rate, and non - standard treatment. The high viral load and non - standard treatment are the main causes for short - term relapse.