基因1型慢性丙型肝炎代偿期肝硬化患者抗病毒治疗后的长期随访研究

Long-term follow-up study of genotype 1 patients with HCV-related compensated cirrhosis treated with pegylated interferon alpha-2a and ribavirin

目的探讨基因1型慢性丙型肝炎代偿期肝硬化抗病毒治疗的长期疗效。方法采用平行对照回顾性队列研究,对基因1型慢性丙型肝炎代偿期肝硬化患者予聚乙二醇干扰素α-2a联合利巴韦林（PR）治疗,予以集落刺激因子对症治疗,5年长期随访并观察其转归。评估疗效、复发率,肝脏瞬时弹性超声成像检测肝脏硬度值（Stiffness值）,比较持续病毒学应答（SVR）组和非持续病毒学应答（NSVR）组的临床事件（肝性脑病、腹水、消化道出血、肝癌或者死亡）发生。结果54例基因1型慢性丙型肝炎代偿期肝硬化患者接受了PR治疗,获得SVR的患者有35例。15例患者在第1次抗病毒治疗后获得SVR,9例、8例、2例、1例患者分别在第2、3、4、5次抗病毒治疗后获得SVR。仅有1例患者在获得SVR6周后出现复发。抗病毒治疗期间,患者的肝硬度值得到不同程度的改善,SVR组治疗后与基线值比较差异有统计学意义（P=0.0004）。结束治疗后的长期随访发现,SVR组患者的肝硬度值有进一步下降的趋势,并能保持在一个较低的水平。而NSVR组患者的肝硬度值没有改善。在平均为60个月的随访中,NSVR组新增3例肝癌患者,SVR组则无人发生。两组临床事件发生频率的差异有统计学意义[腹水：P=0.0168,RR=0.2353（95%CI 0.039~1.422）,HCC：P=0.0391,RR=0.0000]。结论对于基因1型慢性丙肝代偿期肝硬化使用聚乙二醇干扰素α-2a联合利巴韦林能有效抑制病毒,应用集落刺激因子可提高患者治疗依从性。既往治疗失败患者,多次治疗及延长疗程能提高SVR率。获得SVR后的复发率低,能减少肝癌等临床事件的发生,缓解肝硬化进展。

Objective To investigate the effect and clinical outcomes on combination treatment of pegylated interferon alpha‐2a and ribavirin （PR） for hepatitis C virus （HCV） genotype 1 patients with compensated cirrhosis .Methods In our parallel retrospective cohort study ,HCV genotype 1 patients with HCV related compensated cirrhosis received PR therapy and symptomatic treatment with colony‐stimulating factors （CSF） .And the patients undertook a long‐term follow‐up for 5 years .The efficacy and recurrence rate of antiviral therapy were evaluated .Transient elastography （TE） was used in liver stiffness measurement （ LSM ） . The occurrences of clinical events , including hepatic encephalopathy , ascites , gastrointestinal bleeding ,hepatocellular carcinoma （HCC） and death ,was compared between sustained virological response （SVR） group and non‐sustained virological response （NSVR） group .Results Fifty‐four HCV genotype 1 patients with HCV related compensated cirrhosis completed the PR therapy , and 34 （64 .81% ） achieved SVR . Fourteen among 23 patients（65 .22% ） achieved SVR after the first antiviral therapy ,so did 9/14 （64 .29% ） patients after the second ,8/13 （76 .92% ） after the third ,2/3 （66 .67% ） after the forth and 1/1 （100% ） after the fifth .Only one case relapsed at 6 weeks after achievement of SVR .During the antiviral treatment period ,LSM improved to varying degrees ,which showed a significant statistical difference in SVR groups （P= 0 .0004） .During the long‐term follow‐up ,the LSM of SVR group showed a further decline and kept at a low level .However ,there was no improvement of LSM in NSVR group .During the follow‐up for 60 months on average ,there were 3 cases developing HCC in NSVR group ,while 0 in SVR group .Incidencenbsp;of clinical events ,such as ascites [P=0 .0168 ,RR= 0 .2353 （95% CI 0 .0390‐1 .422）] and HCC [P=0 .0391 ,RR= 0 . 0000] ,between the two groups showed significant difference .Conclusion PR therapy can effectively restrain virus replication for HCV genotype 1 patients with HCV related compensated cirrhosis .Combination therapy with CSF can improve treatment compliance .Patients who failed in the previous treatments can acquire SVR via repeated or extended course of PR treatments .Acquisition of SVR can decrease recurrence rate and occurrence of clinical events ,and improve progression of cirrhosis .