Ji Fanpu, Dang Shuangsuo, Cai Zhifang, Xue Hongan, Huang Na, Liu Layang, Zhang Shu, Guo Yonghong, Jia Xiaoli, Wang Yuan, Li Zongfang, Deng Hong
Department of Infectious Disease, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Zhonghua Gan Zang Bing Za Zhi. 2015 Sep;23(9):647-52. doi: 10.3760/cma.j.issn.1007-3418.2015.09.003.
To investigate the efficacy and safety of antiviral treatment in patients with hepatitis C virus (HCV) infection and decompensated cirrhosis and determine the effects of virological response on long-term prognosis.
Sixty-six consecutive,interferon (IFN)-na(i)ve patients with HCV infection and decompensated cirrhosis were enrolled in this prospective study. All patients were given a 48-to 72-week course of IFN plus ribavirin (RBV) combined therapy,with a low accelerating dosage regimen using either:pegylated (PEG)-IFNa-2b at 1.0-1.5 mug/kg/week,PEG-IFNa-2a at 90-180 mug,or standard IFN-a-2b at 3MU,every other day.RBV was given at 800 to 1000 mg/day. All patients were routinely monitored for adverse drug reactions and virological response.Effects of treatments on patient survival were assessed by Kaplan-Meier analysis.
At the end of treatment,74.2% of patients were HCV RNA-negative,with 45.5% having achieved sustained virological response and 28.8% having relapsed;the remaining 25.7% of patients showed non-virological response (NVR). Among the patients with HCV genotype 1, 65.9% achieved end-of-treatment virological response (ETVR) and 34.1% achieved SVR;among the patients with HCV genotype 2,90.9% achieved ETVR and 68.2% achieved SVR. The positive and negative predictive values of early virological response (EVR) for ETVR were 95.7% and 75.0% respectively, and for SVR were 65.2% and 100% respectively. Compared with baseline,patients who achieved ETVR had better liver function,as evidenced by changes in levels of total bilirubin,alanine aminotransferase and albumin,as well as prothrombin activity and Child-Pugh score (t =4.564,11.486,2.303,2.699,3.694 respectively, all P less than 0.05).Compared with the NVR patients, the ETVR patients had lower risk of hepatic decompensation and hepatocellular carcinoma, and had improved survival (x2=18.756,6.992,7.580, respectively, all P less than 0.05).Twelve (18.2%) patients experienced serious adverse events,with 10 requiring premature treatment withdrawal and 2 dying.
Antiviral treatment for patients with HCV infection and decompensated cirrhosis using interferon in a low accelerating dosage regimen in combination with ribavirin is feasible.Patients who achieved ETVR had significantly improved long-term prognosis.
探讨抗病毒治疗对丙型肝炎病毒（HCV）感染失代偿期肝硬化患者的疗效及安全性，并确定病毒学应答对长期预后的影响。
本前瞻性研究纳入了66例连续的、未接受过干扰素（IFN）治疗的HCV感染失代偿期肝硬化患者。所有患者均接受48至72周的IFN联合利巴韦林（RBV）治疗，采用低剂量加速给药方案，即：聚乙二醇化（PEG）-IFNα-2b，1.0 - 1.5μg/kg/周；PEG-IFNα-2a，90 - 180μg；或标准IFN-α-2b，3MU，隔日一次。RBV剂量为800至1000mg/天。所有患者均常规监测药物不良反应及病毒学应答。采用Kaplan-Meier分析评估治疗对患者生存的影响。
治疗结束时，74.2%的患者HCV RNA阴性，45.5%实现持续病毒学应答，28.8%复发；其余25.7%的患者表现为无病毒学应答（NVR）。在HCV基因1型患者中，65.9%实现治疗结束时病毒学应答（ETVR），34.1%实现持续病毒学应答（SVR）；在HCV基因2型患者中，90.9%实现ETVR，68.2%实现SVR。早期病毒学应答（EVR）对ETVR的阳性和阴性预测值分别为95.7%和75.0%，对SVR的阳性和阴性预测值分别为65.2%和100%。与基线相比，实现ETVR的患者肝功能更好，总胆红素、丙氨酸氨基转移酶和白蛋白水平、凝血酶原活性及Child-Pugh评分均有变化（t分别为4.564、11.486、2.303、2.699、3.694，均P<0.05）。与NVR患者相比，ETVR患者发生肝失代偿和肝细胞癌的风险更低，生存率更高（χ²分别为18.756、6.992、7.580，均P<0.05）。12例（18.2%）患者发生严重不良事件，10例需要提前终止治疗，2例死亡。
采用低剂量加速给药方案的干扰素联合利巴韦林对HCV感染失代偿期肝硬化患者进行抗病毒治疗是可行的。实现ETVR的患者长期预后显著改善。
