EASL Publishes Revised Clinical Practice Guidelines for Chronic Hepatitis B

StephenW

EASL Publishes Revised Clinical Practice Guidelines for Chronic Hepatitis B                                Category: HBV Treatment  
Published on Tuesday, 17 July 2012 00:00
Written by Liz Highleyman               
                                                                                                

HBV © Russell Kightley

                                       
               
               
                The European Association for the Study of the Liver (EASL) recently revised its clinical practice guidelines for the management of patients with chronic hepatitis B virus (HBV) infection. The new recommendations were announced at the International Liver Congress in April in Barcelona and published in the July 2012 Journal of Hepatology.
         Approximately one third of the world’s population has evidence of past or present HBV infection and 350-400 million people have chronic hepatitis B, the guidelines authors noted.
        EASL's hepatitis B clinical practice guidelines were originally released in October 2008. They are intended to assist physicians and other healthcare providers, as well as patients and interested individuals, in the clinical decision-making process by describing a range of generally accepted approaches for the diagnosis, treatment, and prevention of specific liver disease, according to a press release issued at the Congress.
        The latest version includes modified indications for liver biopsy and treatment for hepatitis B "e" antigen (HBeAg) negative patients, new stopping rules for pegylated interferon alfa, amended recommendations for patients with partial virological response after 12 months on entecavir (Baraclude) or tenofovir (Viread), and recommendations for less frequent HBV DNA testing when using these 2 drugs.
        The guidelines also feature a new switch strategy -- replacing the previous add-on strategy -- for people who develop drug resistance, and more detailed recommendations for specific subgroups including pregnant women and people with suppressed immunity.
        The revised recommendations reflect new data that have become available since the previous guidelines were published, but the authors acknowledge that areas of uncertainty still exist and "therefore clinicians, patients, and public health authorities must continue to make choices on the basis of the evolving evidence."

•                 The questions the panel members addressed included:
•                 How should liver disease be assessed before therapy?
•                 What are the goals and endpoints of treatment?
•                 What are the definitions of response?
•                 What is the optimal approach to first-line treatment?
•                 What are the predictors of response?
•                 How should resistance be defined and managed?
•                 How should treatment be monitored?
•                 When can treatment be stopped?
•                 How should special groups be treated?
•                 What are the current unresolved issues?
  

        HBV Detection and Monitoring        HBV DNA detection and viral load measurement are essential for diagnosis, deciding whether to treat, and subsequent monitoring of patients, the authors wrote. HBV DNA levels should be expressed in International Units (IU/mL) to enable accurate comparison. Clinicians should look for other causes of chronic liver disease in people with HBV, including hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis delta virus (HDV), and HIV coinfections.
        The panel recommended liver biopsies for determining the degree of necro-inflammation and fibrosis, as this can inform decisions about when to start treatment. But a biopsy is usually not necessary for patients with clinical evidence of cirrhosis or those for whom treatment would be indicated regardless of biopsy findings.
        The non-invasive transient elastography or FibroScan method -- which is more widely used in Europe than in the U.S. -- "offers high diagnostic accuracy for the detection of cirrhosis, although the results may be confounded by severe inflammation associated with high ALT levels and the optimal cut-off of liver stiffness measurements vary among studies," according to the authors.
        HBV Treatment        The goal of hepatitis B treatment is to improve quality of life and extended survival by preventing progression to cirrhosis, hepatocellular carcinoma, decompensated or end-stage liver disease, or death, the authors wrote. Therapy that produces sustained suppression of HBV replication typically leads to reduction in histological activity (inflammation and cell turnover), which lessens the risk of negative clinical outcomes.
        However, chronic HBV infection cannot be completely eradicated due to the persistence of covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. As with HIV, this may explain why HBV can reactivate if treatment is discontinued or immune function changes. Furthermore, integration of HBV genes into the host genome may contribute to development of cancer.
        The ideal endpoint of treatment is hepatitis B surface antigen (HBsAg) loss, but this is usually not achievable with current therapy, according to the panel members. A more realistic endpoint is the sustained virological remission.
        For both HBeAg positive and HBeAg negative patients, the ideal endpoint is sustained HBsAg loss after stopping treatment, with or without anti-HBs antibody seroconversion. For HBeAg negative patients, virological and biochemical response (ALT normalization) is a "satisfactory" endpoint associated with improved prognosis. For HBeAg positive patients who do not achieve anti-HBe seroconversion, maintained virological remission with long-term antiviral therapy is the next best endpoint.
        Indications for treatment are generally the same for both HBeAg positive and negative patients, based mainly on a combination of 3 criteria: serum HBV DNA levels, serum ALT levels, and severity of liver disease. Treatment should be considered if a person has HBV DNA > 2000 IU/ml, ALT above the upper limit of normal, and biopsy evidence of moderate-to-severe necro-inflammation or at least moderate fibrosis.
        Hepatitis B treatment options include the nucleoside analogs entecavir, emtricitabine (Emtriva), lamivudine (Epivir or 3TC), and telbivudine (Tyzeka) and the nucleotide analogs adefovir (Hepsera) and tenofovir (Viread); several of these agents are also used to treat HIV (for which purpose they are known as nucleoside/nucleotide reverse transcriptase inhibitors, or NRTIs).
        Conventional and pegylated interferon -- the mainstay of hepatitis C treatment -- may also be used to treat chronic hepatitis B, alone or in combination with nucleoside/nucleotide analogs. Depending on patient and disease characteristics, hepatitis B treatment may entail either a finite course of therapy with nucleoside/nucleotide analogs or interferon, or else ongoing maintenance therapy with nucleoside/nucleotide analogs.
        Entecavir and tenofovir are potent inhibitors of HBV with a high barrier to resistance, and therefore "can be confidently used as first-line monotherapies," the authors recommended. While lamivudine is inexpensive, resistance is common when it is used as monotherapy. Adefovir is less effective, more expensive, and more prone to resistance than tenofovir. Telbivudine is a potent inhibitor of HBV replication, but has a lower barrier to resistance.
        Most people achieve sustained virological remission with either entecavir or tenofovir monotherapy. Combination nucleoside/nucleotide therapy -- which makes it harder for the virus to develop resistance -- may be used in difficult-to-treat cases (for example primary non-response or viral breakthrough), but according to the authors "there are as yet no data" to indicate whether starting with a combination regimen is more advantageous for treatment-naive patients.
        The clinical practice guidelines cover treatment considerations for special patient groups including people with cirrhosis, liver transplant recipients, kidney transplant recipients and dialysis patients, HIV/HBV coinfected people (who are advised to include one or more drugs active against both viruses in their antiretroviral regimen), patients coinfected with HCV or HDV (who may experience more severe liver disease), people with acute hepatitis B, healthcare workers, children, and pregnant women (including prevention of perinatal HBV transmission).
        The full EASL hepatitis B clinical practice guidelines are available for free online at www.journal-of-hepatology.eu/article/S0168-8278(12)00167-5/fulltext.
        7/17/12
        Reference
        European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of Chronic Hepatitis B Virus Infection. Journal of Hepatology 57(1):167-85. July 2012.
        Other Source
        EASL. New Clinical Practice Guidelines on Alcoholic Liver Disease Published, Hepatitis B Guidelines Revised. Press release. April 19, 2012.
        

StephenW

欧洲肝病学会发布了经修订的慢性乙型肝炎的临床实践指南

详情
    分类：乙肝治疗
    上周二，17七月2012 00:00
    书面利兹Highleyman



欧洲肝脏研究协会（EASL）最近修订了它的管理与慢性乙型肝炎病毒（HBV）感染患者的临床实践指南。在4月的国际肝病大会在西班牙巴塞罗那宣布了新的建议，并在2012年七月中华肝脏病杂志出版。

约世界人口的三分之一，过去或现在的乙肝病毒感染的证据和350-400万人患有慢性乙型肝炎，指引的作者指出。

欧洲肝病学会乙肝的临床实践指南最初发布于2008年10月。他们的目的是协助医生和其他医疗服务提供者，以及患者和有兴趣的人士，在临床决策过程中所描述的范围内普遍接受的方法和具体肝脏疾病的诊断，治疗，预防，根据按在大会上发出的释放。

最新版本包括肝活检和治疗乙肝的“e”抗原（HBeAg）阴性的患者，停止新的聚乙二醇干扰素的规则，修订12个月后，恩替卡韦（博路定）或泰诺福韦部分病毒学应答的患者建议修改的迹象（VIREAD），使用这两种药物时，那么频繁的HBV DNA检测的建议。

准则还配备了一个新的转换策略 ​​- 人谁开发耐药，具体分组，包括孕妇和免疫抑制的人更详细的建议 - 取代了以前的附加战略。

修订后的建议反映了新的数据，已成为提供自上次指引发表，但作者承认领域的不确定性仍然存在，“因此，医生，患者和公共卫生当局必须继续不断变化的证据的基础上选择“

    问题解决小组成员包括：
    应该如何肝病治疗前评估？
    的治疗目标和终点是什么？
    有什么反应的定义是什么？
    第一线治疗的最佳方法是什么？
    有什么反应的预测？
    电阻应如何界定和管理？
    应该如何处理被监视吗​​？
    什么时候可以停止治疗呢？
    特殊群体应该如何对待？
    什么是目前尚未解决的问题是什么？

乙肝病毒的检测和监测

HBV DNA检测和病毒载量的测量是必不可少的诊断，决定是否治疗，患者的后续监测，作者写道。 HBV DNA水平应表示，在国际单位（IU /毫升），以便准确的比较。临床医生应寻找其他原因引起的慢性肝病，包括肝炎病毒（HAV），丙型肝炎病毒（HCV），丁型肝炎病毒（HDV），与艾滋病毒混合感染乙肝病毒的人。

该小组的建议确定的坏死炎症和纤维化程度的肝活检，因为这可以决定告知何时开始治疗。但活检通常是没有必要为肝硬化或治疗对他们来说，将表示，不管活检结果的临床证据的患者。

非侵入性的瞬时弹性或FibroScan方法 - 这是在欧洲比在美国更广泛的 - “提供诊断为肝硬化的检测精度高，但结果可能会混淆和严重的炎症与高ALT水平相关肝脏硬度测量的最佳切断的不同而有所差异研究“，根据作者。
乙肝治疗

乙肝治疗的目标是防止进展为肝硬化，肝癌，失代偿期或终末期肝脏疾病，或死亡，提高生活质量和延长生存期，作者写道。通常的治疗方法，产生持续抑制乙肝病毒复制减少组织活动（炎症和细胞的营业额），从而减少了风险负的临床疗效。

然而，慢性乙肝病毒感染不能被彻底根除，由于共价闭合环状DNA（cccDNA）感染的肝细胞的细胞核中的持久性。与艾滋病毒，这也许可以解释为什么乙肝病毒可以激活，如果治疗是终止或免疫功能的变化。此外，整合到宿主基因组的HBV基因可能有助于癌症的发展。

理想的治疗终点是乙型肝炎表面抗原（HBsAg）的损失，但目前的治疗，这通常是不实现的，根据小组成员。一个更为现实的终点是持续病毒学缓解。

理想的终点为HBeAg阳性和HBeAg阴性患者，持续HBsAg的损失后停止治疗，或未经抗-HBs抗体转阴。对于HBeAg阴性患者，病毒学和生化反应（ALT正常化）是一个“令人满意”的终点，改善预后。对于HBeAg阳性患者没有达到抗-HBe血清转换，保持着长期的抗病毒治疗的病毒学缓解是下一个最好的终点。

HBeAg阳性和阴性的患者主要是基于3标准的组合，血清HBV DNA水平，血清ALT水平，肝脏疾病的严重程度，治疗适应症大致相同。如果一个人有血清HBV DNA> 2000 IU /毫升，ALT高于正常上限，活检中度至重度坏死炎症或至少中度纤维化的证据，应考虑治疗。

B型肝炎的治疗方法包括核苷类似物恩替卡韦，恩曲他滨（Emtriva），拉米夫定（拉米或3TC）和替比夫定（TYZEKA）和核苷酸类似物阿德福韦（阿德福韦酯）和替诺福韦（VIREAD）;几个这些药物也用于治疗艾滋病毒（为此他们称为核苷/核苷酸逆转录酶抑制剂，或NRTI的）。

传统和聚乙二醇干扰素 -  C型肝炎治疗的支柱 - 也可能被用于治疗慢性乙型肝炎，单独或结合核苷/核苷酸类似物。乙肝治疗根据病人和疾病的特点，可能需要与有限的治疗过程中核苷/核苷酸类似物或干扰素或核苷/核苷酸类似物与其他正在进行的维持治疗。

恩替卡韦和替诺福韦是乙肝病毒抑制剂，具有很高的障碍阻力，因此“可以自信作为第一线单一疗法”，作者建议。而拉米夫定是廉价的，阻力是共同的，当它被用来作为单一。阿德福韦是更有效，更昂贵，更容易比替诺福韦阻力。替比夫定是乙肝病毒复制的强效抑制剂，但有阻力较低的屏障。

大多数人实现持续使用恩替卡韦或替诺福韦单药治疗的病毒学缓解。可用于难以治疗的情况下，结合核苷/核苷酸治疗 - 这使得它的病毒产生抗药性更难 - （例如主要的非反应或病毒突破），但根据作家“，也有作为还没有数据表明是否与组合方案开始治疗过的病人更有利。

临床实践指南涵盖包括治疗肝硬化，肝移植，肾移植和透析患者，艾滋病毒/ HBV合并感染的人（应包括在一个或多个活性药物对两种病毒的抗逆转录病毒疗法的人的特殊患者群体的考虑），患者同时感染HCV或HDV（可能会遇到更严重的肝脏疾病），急性乙型肝炎，医护人员，儿童，孕妇（包括预防母婴传播）的人。

全欧洲肝病学会乙肝临床实践指导方针，是提供免费在线www.journal-of-hepatology.eu/article/S0168-8278（12）00167-5/fulltext的。

12年7月17日

参考

欧洲肝脏研究协会。欧洲肝病学会临床实践指南：慢性乙型肝炎病毒感染的管理。 [肝病57（1）:167-85。 2012年7月。

其他来源

欧洲肝病学会。新的酒精性肝病的临床实践指南的发布，乙型肝炎准则的修订。新闻稿。 2012年4月19日。