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[AASLD独家]丙型肝炎合并肝硬化患者的治疗与监测
——  作者:Paul Y. Kwo    时间:2015-11-23 05:27:14    阅读数: 249

美国印第安那大学医学院  Paul Y. Kwo 教授访谈
  《国际肝病》:丙型肝炎肝硬化特别是失代偿期肝硬化患者进行抗病毒治疗最大的困难是什么?
  Kwo教授:在直接作用抗病毒药物(DAA)的时代下,代偿期肝硬化患者可获得与无肝硬化患者相似的持续病毒学应答(SVR)率(85%~90%)。而在此之前,肝硬化患者应用干扰素治疗耐受性较差,失代偿期肝硬化患者考虑到安全性也不建议使用。因此,这是我们取得的一项重大进展。大多数国家所面临的挑战是这些药物是否进入患者的可选择范围,而不是具体疗效的问题。这仍需要进行相关的临床研究,相信在药物的疗效方面不会有太大的地域性差异。重要的是,应及时筛选出失代偿期肝硬化患者,确定是否适合应用雷迪帕韦(ledipasvir)/索非布韦(sofosbuvir)+利巴韦林或者索非布韦/达卡他韦(daclatasvir)+利巴韦林。这两种治疗方案均可获得非常高的SVR率。
  What we have found in the era of direct-acting antiviral agents is that the compensated cirrhosis patients actually achieve SVR rates not too differently from those without cirrhosis. That is a major advance. Our previous interferon-based therapies were not well tolerated in cirrhosis and we could not really give them safely in decompensated cirrhosis. Now that we have entered the field of direct-acting antiviral agents for decompensated cirrhosis, what we have been able to demonstrate is that we get sustained response rates of 85%-90% which are not that different (5-10% less) than what we see in the compensated and non-cirrhotic population. The challenge to be faced by most countries is getting access to these medicines for decompensated individuals. It is not a matter of poor efficacy. The studies still need to be done in Asia and particularly China, but it is highly likely that we are not going to see regional differences in sustained response rates. Rather it is going to be ensuring that those with decompensated cirrhosis are recognized, particularly in countries like China, and then making sure they are evaluated to determine if they are candidates for therapy using ledipasvir/sofosbuvir with ribavirin or sofosbuvir /daclatasvir with ribavirin. These regimens can achieve excellent sustained response rates if there is access to the therapies.
  《国际肝病》:目前对基因1型HCV感染肝硬化患者的标准治疗是什么?
  Kwo教授:对于基因1型HCV代偿期肝硬化患者,有多种治疗选择,AASLD/IDSA以及EASL官网均提供了对上述治疗的推荐及讨论,可供参考。目前,代偿期肝硬化患者治疗的SVR率非常高,与无肝硬化者的治疗并无差异,不过需要将治疗疗程调整至24周,并且利巴韦林在这一患者人群中非常有效,应联合DAA治疗。
  For compensated cirrhosis patients with hepatitis C genotype 1, there are multiple treatment options. I would refer you to the AASLD/IDSA website or the EASL website where all of these therapies are discussed. All of these in the compensated patient lead to excellent SVR rates and clinicians who treat these individuals can be very confident they will be able to achieve excellent sustained response rates with all of these therapies. We should consider that those with hepatitis C and compensated cirrhosis are not different from those without cirrhosis. The regimens may need to be changed minimally with durations out to 24 weeks and ribavirin is often very useful in this patient population, but the expectation would be that SVR rates would not be different.
  《国际肝病》:如何对成功抗病毒治疗后的进展期肝纤维化或肝硬化患者进行监测?
  Kwo教授:对于这部分患者仍然需要接受密切随访,以排除发生肝细胞肝癌(HCC)的风险。尤其在亚洲,患者可能同时存在HCV和HBV感染,HBV感染是HCC的重要风险因素,所有HCV肝硬化患者都必须接受定期筛查,如每6个月应用超声进行HCC的筛查。此外,必须对他们进行关于失代偿或疾病进展的定期监测,以免发生静脉曲张、腹水等并发症。迄今为止,已有研究表明,在越来越多的已得到治愈的患者中,年龄越大,发生HCC的风险就越高。所以,需要再次强调这些肝硬化患者的长期监测。
  It is important to let the patient know that they have been cured of the virus but not of their liver disease. They still need to be closely followed to determine if they develop hepatocellular carcinoma, particularly in Asia where people may have hepatitis C and hepatitis B infection. Hepatitis B infection is a tremendous risk factor for HCC. All of these cirrhosis patients with hepatitis C will have to be entered into regular screening programs for HCC with ultrasound every six months. In addition, they are going to have to be regularly monitored for decompensation or disease progression. We need to make sure they don’t develop varices or ascites. What has been shown thus far amongst the increasing number of people who have been cured, is that the older you are the more at risk you are for developing hepatocellular carcinoma. So again, for physicians who treat these cirrhosis patients, they will be able to achieve SVR rates at far higher rates than they would have been able to do in the era of interferon-based therapies, but they have to let their patients know that even though they are given a well tolerated therapy and achieved SVR, their liver disease is not gone and they have to see their physician regularly to make sure their liver stays well-compensated.

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