[APASL2014]丙型肝炎肝移植的新视野

新西兰肝移植协会副会长、奥克兰大学Ed Gane教授于昨日就丙肝复发所致肝移植的相关问题指出澳大利亚和新西兰地区近十年内因乙肝所致肝移植的需求量基本保持稳定，而丙肝患者肝移植的需求量却呈上升趋势。

Ed Gane教授

Gane教授发言的重点集中在治疗手段上，他列举了相关研究数据并指出IFN+RBV的联合治疗方案对于很多“天生存在缺陷”的患者疗效较差。患者对之前治疗反应较差、免疫系统处于抑制状态以及身体难以耐受等因素的综合作用导致治疗成功率低下。

有三种新型药物可明显改善治疗反应性。其中NS3A蛋白酶抑制剂、boceprevir和telaprevir得到广泛认可。在欧洲，一项由Coilly A等人开展的关于boceprevir的小规模多中心研究结果显示受试者的持续病毒学应答（SVR）为71% (n=7)，尽管疗效如此显著，但由于其可引起肾功能不全、耐受性下降以及给药方案复杂、仅对基因1型HCV有效而限制了其使用。

核酸聚合酶抑制剂sofosbuvir前景良好，Gane教授公布了自己课题组部分尚在研究中的试验结果，数据显示处于代偿期的丙肝复发者SVR为73％，而失代偿期患者的病情有望通过sofosbuvir治疗得以缓解。另一项研究结果显示，64%的受试者对治疗反应良好，主要表现为“黄疸、腹水、凝血障碍以及肝性脑病短时间内得到改善”。SOF+RBV联合治疗的受试者中，有60％的SVR水平可持续12周。

Gane教授继续补充道，有研究结果显示直接作用抗病毒药物(DAAs)对于非肝移植患者疗效更为显著，肝移植术前给予SOF+RBV联合治疗可预防2/3的患者丙肝复发，目前的治疗手段甚至可以挽救需要行肝移植患者的病情。

Gane教授最后总结称，今年亚太肝脏研究协会年会(APASL)的主题是迎来肝脏病学新纪元，这在丙肝肝移植上得到了充分体现。

原文阅读》》》The Changing Landscape of Transplantation for HCV

While the need for transplantation due to hepatitis B infection has remained relatively constant for Australia and New Zealand for the last decade, the need due to hepatitis C has increased dramatically. Prof. Ed Gane spoke yesterday on how to monitor transplant patients for recurrent HCV. 

The majority of Dr. Gane’s talk focused on treatment. He showed data from several studies that pointed to the ineffectiveness of IFN/RBV combination in many of these “born to lose” patients. The combination of previous non-response, immunosuppression, and poor tolerability make successful treatment unlikely. 

The three new classes of drugs have drastically improved response.  Among the NS3A protease inhibitors, boceprevir and telaprevir are the most promising. While the numbers were small, a multicentre European study on transplant patients by Coilly A et al. demonstrated an SVR of 71% (n=7) with boceprevir. Yet even with these rates, there is a risk of renal dysfunction, and the poor tolerability, complex dosing regimen, and ineffectiveness in genotypes other than genotype 1 HCV  will limit their efficacy. 

The polymerase complex inhibitor sofosbuvir shows greater promise. Prof. Gane presented data, from an on-going study by his group, showing that 73% of patients with compensated recurrent HCV have achieved SVR.  In decompensated patients, sofosbuvir offers tangible hope of recovery. In a compassionate access program, 64% responded well to the treatment, with “rapid resolution of jaundice, ascites, coagulopathy, and encephalopathy.” 60% maintained an SVR at week 12 on SOF/RBV combination therapy.

Prof. Gane continued, bringing to light studies showing the even greater effectiveness of combining DAAs in non-transplant patient; how pre-transplant treatment with SOF/RBV has also been shown to prevent recurrence in 2/3 patients; and now therapy can even rescue patients from the need for a transplant. 

“The theme for this year’s APASL is A New Era Begins,” concludes Prof. Gane, “nowhere is this more evident than in transplantation for HCV.”

来源：APASL 2014 daily news