编者按：第53届欧洲肝脏研究学会（EASL）年会召开期间，EASL发布了五部临床实践指南，涉及丙型肝炎、失代偿肝硬化、酒精性肝病、肝细胞癌和戊型肝炎。EASL前秘书长、法国巴黎东区大学作为丙型肝炎指南制定小组组长，在会上介绍了最新版指南内容。《国际肝病》前方记者在第一时间采访到Pawlotsky教授，请他为我们解读指南的重要更新点（点击下载指南全文）。

 

2018年EASL丙型肝炎治疗指南的重要更新

 

在本届EASL年会的开始，我们发布了2018年EASL丙型肝炎治疗指南。我认为该版指南最重要的更新推荐意见是提供了泛基因型HCV感染的药物治疗方案，目前，有两种非常有效、安全、耐受性良好的泛基因型药物方案：索磷布韦/维帕他韦（velpatasvir）和glecaprevir/pibrentasvir，这两种方案应用不同疗程，均被推荐用于基因1～6型等所有基因型HCV感染患者的治疗。

 

该版指南另外一个特别重要的更新内容是以增加患者的治疗可及性为目的，提供了简化治疗的机会。简化治疗的意思就是尽可能少的治疗前评估，应该采用非常简单的方法：天冬氨酸氨基转移酶（AST）/血小板（PLT）比值指数（APRI）或FIB-4[基于患者年龄、AST、PLT和丙氨酸氨基转移酶水平（ALT）]，对患者的肝脏疾病严重度进行评估，应该对病毒复制进行确认，但是，并不需要进行HCV基因分型检测，患者就可以应用索磷布韦/维帕他韦方案治疗12周，或者应用glecaprevir/pibrentasvir方案治疗（无肝硬化和肝硬化患者的疗程分别为8周和12周），治疗结束后，应该对持续病毒学应答（SVR）进行评估。这是非常简化的策略，是该版EASL指南的重大突破，可以增加患者的治疗可及性。

 

大多数“难治性”患者相对容易治疗

 

现在，丙型肝炎的治疗在进步，极少有难治性患者，绝大多数患者可以获得很高的SVR率。基因3型HCV感染肝硬化患者稍微更难治一点儿，他们仍然需要应用更长疗程的治疗，或者加用第三种药物，这也是我们推荐这些患者应用glecaprevir/pibrentasvir治疗更长时间的原因，初治患者和经治患者分别治疗12周和16周，或者应用索磷布韦/维帕他韦/voxilaprevir三联治疗。应用这些治疗方法，患者可以获得很高的SVR率。失代偿期肝硬化患者仍然是应用索磷布韦/维帕他韦+利巴韦林（应用利巴韦林的唯一患者人群）治疗的指征。但是，总体上，对许多难治性患者人群已经提供了解决方案，大多数患者相对容易治疗，可以获得很高的SVR率。

 

研发HCV疫苗并非必要

 

现有的直接抗病毒药物对于治疗丙型肝炎非常有效，将来不再需要HCV疫苗，如果有HCV疫苗可用，显然非常好，但是问题是在技术上和科学上，HCV疫苗的研发非常困难。应用新的治疗，我们可以处理丙型肝炎的问题。目前的挑战不是研发HCV疫苗，而是发现HCV感染患者，为他们提供更高的治疗可及性。

 

实现2030年全球消灭HCV感染目标的最大挑战

 

实现2030年全球消灭HCV感染的目标，有两大挑战：第一大挑战是筛查和发现所有HCV感染患者；第二大挑战是使筛查发现的患者得到治疗，即确保已经诊断为HCV感染的患者得到有效治疗。应用目前市场上的新药和泛基因型治疗方案：glecaprevir/pibrentasvir和索磷布韦/维帕他韦，相信绝大多数患者可以得到治愈。再次强调，筛查所有HCV感染患者，保证所有患者的治疗可及性，使他们可以接受治疗非常重要。

 

Prof. Pawlotsky: We released the EASL Recommendations on the Treatment of Hepatitis C 2018 at the beginning of this International Liver Congress meeting. I think the most important new recommendations are for pan-genotypic drug regimens. We currently have two very efficient, safe and well-tolerated pan-genotypic regimens - sofosbuvir and velpatasvir, and glecaprevir and pibrentasvir. Both of these are recommended for different durations for patients infected with all HCV genotypes. The two regimens can be used for genotypes 1 through 6. Another very important new inclusion in the Guideline is that we offer the opportunity for simplified therapy with the goal of improved access to care. Simplified therapy means there is minimal pretreatment assessment. The severity of liver disease should be assessed using a very simple method, APRI or FIB-4. Viral replication should be confirmed. Then there is no need to do genotyping and the patient is treated either with sofosbuvir/velpatasvir for 12 weeks, or with glecaprevir/pibrentasvir for 8 weeks in non-cirrhotics or 12 weeks in cirrhotics. SVR should be assessed and that completes therapy. It is a very simplified approach and is a major breakthrough in these EASL Guidelines that will improve access to care.

 

Prof. Pawlotsky: There are very few difficult-to-treat patients right now. Our treatments are improving. We achieve high SVR rates in a vast majority of the population. The patients with genotype 3 and cirrhosis are slightly more difficult to treat. They still need either longer therapy or the addition of a third drug. That is the reason why it is recommended to treat these patients for 12 weeks with glecaprevir/pibrentasvir if they are treatment na?ve and 16 weeks if they are treatment experienced, or treat them with the triple combination of sofosbuvir/velpatasvir/voxilaprevir. With this therapeutic approach, SVR rates are very high. Patients with decompensated cirrhosis still have an indication for sofosbuvir/velpatasvir plus ribavirin (the only group which will use ribavirin). But overall, solutions have been provided for many of the difficult-to-treat patient populations, and most patients are relatively easy to treat with very high SVR rates.

 

Prof. Pawlotsky: No, I don’t think we will need HCV vaccines in the future. It would obviously be very nice to have an HCV vaccine, but the problem with that is it is very difficult to make technically and scientifically, and we can probably handle the problem of hepatitis C with the new treatments. The challenge now is not to find a vaccine, but to find the patients and provide them with good access to care.

 

Prof. Pawlotsky: There are two major challenges. The first challenge is to screen and identify all the patients who are infected with HCV. The second challenge is linkage to care - making sure patients who have been diagnosed with HCV infection have access to efficient therapy. I believe that with the new drugs that are now on the market and the pan-genotypic regimens, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir, it will be possible to cure the vast majority of patients. Again, it is important that screening is done, and that patients have linkage to care so that they receive therapy.