Viral hepatitis in 2011: a major step forward[Paris Hepatitis Conference]

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http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02412.x/full
Viral hepatitis in 2011: a major step forward

• Patrick Marcellin
  

This supplement of Liver Internationalprovides the state of the art on the management of patients withhepatitis B and hepatitis C in 2011 as presented at the fourth Paris Hepatitis Conference (PHC). Once again, this year, outstanding international experts will be presenting reviews of the most up-to-date information as well as their opinion on its clinical applications.

Knowledge about viral hepatitis has grown exponentially over the past few years with more and more available information on the virology, natural history and treatment of these diseases. The relevance of this information needs to be clarified for clinicians. The aim of this meeting is to facilitate the translation of the most recent scientific knowledge into daily clinical practice, thus improving the managementof patients with viral hepatitis.

Since the last meeting, historical milestones have been achieved: in chronic hepatitis B, long-term follow-up of patients receiving the most potent available antivirals has shown high sustained virological response(SVR) rates with undetectable hepatitis B virus DNA using sensitive polymerase chain reaction assays, associated with a persistent biochemical response, increasing rates of HBeAg seroconversion andHBsAg loss in HBeAg-positive patients. Furthermore, no or very little resistance was observed and the SVR has been associated with the regression of liver fibrosis even in patients with advanced fibrosis orcirrhosis.

Long-term follow-up studies of responders who have received pegylated interferon have shown a progressive increase in the rate of HBsAg loss. HBsAg loss is the closest thing to a cure of this disease and is associated with an improved prognosis with a decreased risk of decompensation and hepatocellular carcinoma. The quantification of HBsAg has emerged recently as a potential new tool for predicting post-treatment outcome. Indeed, a significant decline in HBsAg levels is associated with a SVRand the probability of HBsAg loss.

A spectacular step forward was made in chronic hepatitis C with the results of phase 3 studies of triple therapy combining protease inhibitors, telaprevir or boceprevir, with pegylated interferon and ribavirin and resulting in approximately 70% SVR. This advance is a simportant as that observed more than 10 years ago with dual therapy combining interferon and ribavirin. And triple therapy will undoubtedly become the new standard of care in the next couple of years in patients infected with HCV genotype 1.

These first-generation triple therapies open a new era and promising results have already been reported with new more potent direct antiviral agents(DAAs), protease inhibitors and polymerase inhibitors, with easier administration schedules, less resistance and a better safety profile.Interestingly, the proof of concept of interferon-sparing DAAcombinations with or without ribavirin has opened the door to short-duration completely oral treatment for chronic hepatitis C.

At the same time, the non-1 genotypes and other difficult-to-treat populations encountered in routine clinical practice must also be considered. New drugs must be developed to effectively treat non-1genotypes, which are common in high-prevalence areas such as genotype 4 in Egypt and the Middle East or genotype 3 in India. Rare genotypes such as 5 and 6 are also common in areas such as South Africa or Asia.Furthermore, clinical trials are also needed in special populations such as human immunodeficiency virus-positive patients, transplant patients and patients with compensated or decompensated cirrhosis in whom hepatitis C virus-related disease can be especially severe.

Finally,genetics have now been shown to play a role in predicting response to therapy. In particular, the polymorphism in the IL28 region has a strong predictive value for a sustained response to the current standard of care, with 80% of SVR in patients with the C/C and 25% inpatients with the T/T allelle. This discovery helps explain thedifferences in efficacy among Asians, Caucasians and Africans who have proportionally less of the C/C pattern respectively. This is a first step to individualized therapy. Further studies are needed to identify more accurate genetic markers, to understand the mechanisms involved in non-response and to apply these markers to new therapies. Furthermore,an understanding of the genetic factors involved in the response to therapy will certainly help explain the mechanisms involved in chronic HCV infection and the progression of liver disease.

The aim of this supplement of Liver International as well as of the PHC is to provide clinicians with the state of theart and its clinical applications in this field to optimize themanagement of patients with hepatitis B and hepatitis C. But our ultimate goal is to provide optimal therapy and the best chance of cure to as many patients as possible, worldwide.


Conflicts of interest
PatrickMarcellin is an investigator, speaker and expert for Roche, ScheringPlough, Gilead, BMS, Novarties, Tibotec and Intermune He receives a grant from Roche, Schering Plough and Gilead. He is an investigator and expert for Vertex, MSD, and Biolex; an expert for Pharmasset and Zymogenetics; and an investigator for Boehringer.

He receives no salary, regular renumeration or royalties from any drug company or owns any stock options.
这种肝补充提供了国际上与乙型肝炎和丙型肝炎病人中，2011年管理的艺术状态肝炎巴黎举行的第四次会议（PHC）的介绍。再次，今年以来，优秀的国际专家将介绍评论最先进的最新信息，以及他们在其临床应用的意见。

病毒性肝炎相关知识在成倍增长，越来越多的可在病毒学，自然史和治疗这些疾病的信息过去几年。此信息的相关需要为临床医生澄清。本次会议的目的是为方便日常临床实践中最新的科学知识转化，从而提高病毒性肝炎患者的管理。

自上次会议后，取得了历史性的里程碑：在慢性乙肝，长期随访接受抗病毒药物的病人提供最有力的证明了高持续病毒学应答（SVR）与乙肝病毒DNA检测不到率使用敏感聚合酶链反应检测，具有持续性的生化反应有关，越来越多的HBeAg血清转换和HBsAg e抗原阳性患者的损失率。此外，没有或很少抵抗观察的SVR已与肝纤维化相关，即使在回归晚期肝纤维化或肝硬化患者。

长期随访谁收到聚乙二醇干扰素反应的研究表明，在HBsAg的损失率逐步增加。 HBsAg转阴是最接近治愈这种疾病，并与一个有着失代偿和肝癌的风险降低改善预后。 HBsAg的定量最近出现作为一个潜在的预测后处理结果的新工具。事实上，在乙肝表面抗原水平显着下降是与一个SVR和HBsAg的损失概率。

一个引人注目的一步是在慢性丙型肝炎的第三期研究，结合三联疗法蛋白酶抑制剂，telaprevir或boceprevir结果与聚乙二醇干扰素和利巴韦林并造成约70％的SVR。这笔预付款是重要的，因为，超过10年前的观察与治疗相结合的双重干扰素和利巴韦林。而三联疗法无疑将成为新的护理标准，两年中与HCV基因型1感染者未来夫妇。

这些第一代三联疗法打开一个新的时代和充满希望的成果已经被新的更有力的直接抗病毒制剂（DAAs），蛋白酶抑制剂和聚合酶抑制剂与易于管理计划，减少阻力和更好的安全性，报道。有趣的是，干扰素保留的DAA组合概念，或没有证据利巴韦林的大门打开了短期完全口服治疗慢性丙型肝炎

与此同时，非1基因型及其他难以治疗在日常临床实践中遇到的，还必须考虑人口。必须开发新的药物能有效治疗非- 1基因型，其中基因型4，如在埃及和中东或印度的基因3型高流行区常见。珍稀品种，如5和6也如南非或亚洲地区常见的。此外，还需要临床试验，如人类免疫缺陷病毒阳性的患者，移植病人和补偿或代偿性肝硬化病人中，其中丙型肝炎病毒相关的疾病可能是特别严重的特殊群体。

最后，遗传学已被证明发挥预测对治疗的反应的作用。特别是，在IL28区多态性有一个持续应对目前的照护标准较强的预测值，80％患者的SVR与C / C和25％的患者的T /吨allelle。这一发现有助于解释，其中亚洲人，非洲人在白种人和疗效差异有比例的谁的C / C型的比例较小。这是一个个体化治疗的第一步。还需作进一步研究，以确定更准确的遗传标记，以了解在非反应所涉及的机制，并应用这些标记的新疗法。此外，对在响应中涉及到的遗传因素的了解治疗必将有助于解释慢性丙型肝炎病毒感染与肝病恶化所涉及的机制。

这一目标的肝国际补充以及初级卫生保健是提供临床医师在这一领域的最新发展水平及其临床应用程序的状态，以优化与乙型肝炎和丙型肝炎，但我们的最终目标是对患者的管理提供最佳的治疗和治愈的最好机会，因为它可能，世界各地的许多病人。
利益冲突

  
2。利益冲突

帕特里克Marcellin是调查员，扬声器和罗氏，先灵葆雅，基列，拜耳，Novarties，Tibotec公司和InterMune公司专家，他收到来自罗氏，先灵葆雅和基列补助。他是一个研究者和专家顶点，MSD和Biolex;一个Pharmasset和ZymoGenetics公司的专家，而且在勃林格调查。

他没有收到工资，定期的薪酬由公司或特许权使用费的任何药物或拥有任何股票期权。

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