Norah A. Terrault医学博士，描述了AASLD最新版本的变化。

StephenW

            Inside the AASLD’s New Hep B Recs               
        

Norah A. Terrault, MD

The American Association for the Study of Liver Diseases (AASLD) recently revised its guidelines for the treatment of chronic hepatitis B virus infection (Hepatology 2016;63:261-283). Norah A. Terrault, MD, director of viral hepatitis research in liver transplantation at the University of California, San Francisco, who helped write the new recommendations, described what has and has not changed in the latest version.
GEN: Are the guidelines a major departure from what the AASLD has recommended in the past?
Dr. Terrault: In contrast to the last guidelines, the focus was placed specifically on day-to-day decisions regarding treatment. There are several new groups for which treatment was recommended, including pregnant women and cirrhotic patients with low-level viremia, and there are specific recommendations of who not to treat. Another notable change is the greater emphasis placed on individualizing the decision, with clinicians and patients discussing the potential harms and benefits of initiating and continuing therapy.
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GEN: Have the preferred therapies changed?
Dr. Terrault: As before, pegylated interferon and the nucleoside analogs (NAs) entecavir (Baraclude, Bristol-Myers Squibb) and tenofovir (Vemlidy, Gilead) are the preferred therapies. Relative to other NAs, tenofovir and entecavir are associated with very low rates of resistance, and they are well tolerated. A number of patient-specific factors may be relevant for selecting one of these NAs over the other. For example, there are more safety data regarding the use of tenofovir in pregnant women.
The guideline does note the importance of adjusting the dose of all NAs in the setting of renal dysfunction and the baseline and annual assessment of renal health in patients treated with tenofovir. The approval of tenofovir greatly diminishes the risk for changes in bone metabolism relative to those associated with the tenofovir disoproxil fumarate formulation of the drug.
GEN: Which groups are not recommended for treatment?
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Dr. Terrault: Treatment is not recommended in pediatric or adult immune-tolerant patients without inflammation or fibrosis. Although the data are limited, there is as yet no evidence of improved outcome with long-term treatment in this group. However, the guidelines stress repeatedly the importance of ongoing monitoring of HBV in untreated patients because of the dynamic nature of chronic HBV. For immune-intolerant patients, levels of alanine aminotransferase should be tested every six months to monitor for transition to more active phases, when ALT levels are elevated.
Antiviral therapy may be considered in immune-tolerant adults over the age of 40 years if there is evidence of significant liver disease, such as inflammation or fibrosis, even if ALT levels are normal. The guidelines also recommend discontinuing therapy after a period of consolidation in hepatitis B e antigen (HBeAg)-positive adults without cirrhosis who seroconvert to anti-HBe on therapy. The period of consolidation therapy should be at least 12 months, but more data are needed to determine whether longer periods of consolidation would further reduce the risk for relapse.
GEN: Are there are new recommendations in pregnant women?
Dr. Terrault: Treatment has been recommended in hepatitis B surface antigen (HBsAg)-positive pregnant women with HBV DNA levels greater than 200,000 IU/mL to prevent perinatal transmission. Tenofovir is the only drug among the three preferred therapies—peginterferon, entecavir and tenofovir—that has been studied in pregnant women, and most studies have initiated therapy at 28 to 32 weeks of gestation.
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GEN: What about patients with loss of HBsAg?
Dr. Terrault: HBsAg loss is the desired goal of treatment, but it is infrequently achieved, particularly with NAs. The guidelines suggest treatment can be discontinued after HBeAg loss but that there is insufficient evidence to make this a strong recommendation. Again, this is a scenario in which a discussion between the clinician and patient regarding the risks and benefits of treatment discontinuation is warranted. Of note, discontinuation of therapy is not recommended in patients with cirrhosis. If treatment is stopped, surveillance for relapse is essential. Monitoring patients for ALT flares, recurrent viremia and clinical decompensation should be conducted every three months for at least one year after treatment is discontinued.
GEN: Which patients with chronic HBV should remain on long-term treatment?
Dr. Terrault: As highlighted by the prior comments, indefinite antiviral treatment is generally recommended for chronic HBV patients with cirrhosis because of concern about decompensation with virologic relapse. Treatment also should be continued in any HBsAg-positive adult with decompensated cirrhosis regardless of HBeAg status, ALT level or HBV DNA level.
GEN: Assuming HBV therapies are well tolerated and cost is not an issue, isn’t the best strategy to keep all patients with detectable HBV on therapy indefinitely?
Dr. Terrault: The primary argument against use of indefinite therapy in all patients with chronic HBV is that not all patients require therapy to minimize their risk for liver-related complications. Until we have a curative therapy, our treatment goals are to identify those for whom treatment provides benefit and continue that treatment for as long as needed for benefit. For some patients treatment may be indefinite, but for others, a reduced course of therapy will achieve the desired end points. Another argument against indefinite therapy is compliance even when the treatment is well tolerated.
GEN: What is the likelihood of future modifications in HBV treatment guidelines?
Dr. Terrault: HBV therapeutics are evolving, so I anticipate future modifications to the HBV treatment guidelines will be necessary. In addition, more data from natural history cohort studies on the benefits of antiviral therapy may lead to changes in recommendations regarding when to start and when to stop treatment. Finally, there were some aspects of HBV management in special populations, such as those coinfected with hepatitis D virus or HIV who will need to be addressed in future guidance documents.
—Compiled by Ted Bosworth

StephenW

在AASLD的新Hep B Recs

Norah A. Terrault医学博士，肝脏病毒性肝炎研究主任在加利福尼亚大学旧金山分校帮助撰写新建议的时候，描述了最新版本的变化。

美国肝病研究协会（AASLD）最近修订了治疗慢性乙型肝炎病毒感染的指南（Hepatology 2016; 63：261-283）。 Norah A. Terrault医学博士，肝脏病毒性肝炎研究主任在加利福尼亚大学旧金山分校帮助撰写新建议的时候，描述了最新版本的变化。

GEN：这个准则与AASLD在过去推荐的方面有很大的不同吗？

Terrault博士：与最近的指南相比，重点放在了关于治疗的日常决定。有几个新的治疗组被推荐，包括怀孕妇女和低水平病毒血症的肝硬化患者，并有具体的建议是谁不治疗。另一个显着的变化是更多地强调个性化决策，临床医生和患者讨论启动和继续治疗的潜在危害和好处。
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GEN：首选疗法改变了吗？

Terrault博士：如前所述，聚乙二醇化干扰素和核苷类似物（NAs）恩替卡韦（Baraclude，Bristol-Myers Squibb）和替诺福韦（Vemlidy，Gilead）是首选疗法。相对于其他NAs，替诺福韦和恩替卡韦与非常低的相关性，一定数量的患者特异性力可能与其中一种相关。例如，有更多关于在孕妇中使用替诺福韦的安全数据。

该指南确实注意到在替诺福韦治疗的患者肾功能障碍和肾脏健康状况的基线和年度评估中调整所有NAs剂量的重要性。替诺福韦的批准与该药物的替诺福韦地索普尔富马酸盐配方相关

GEN：哪些组不推荐治疗？
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Terrault博士：在没有炎症或纤维化的儿科或成人免疫耐受患者中不推荐治疗。虽然数据有限，但仍有证据表明，该组长期治疗有改善的结果。 （1）由于慢性HBV的动态性质，未治疗患者HBV的持续监测最重要。对于免疫耐受患者，应每六个月测试丙氨酸氨基转移酶水平，以监测当ALT水平升高时向更活跃期转变

如果存在明显的肝脏疾病，如炎症或纤维化，即使ALT水平正常，也可以考虑在40岁以上的免疫耐受成年人中进行反病毒治疗。该规则还建议在乙型肝炎e抗原（HBeAg）阳性成年人巩固一段时间后不停止治疗，而没有肝硬化的血清转化为抗HBe治疗。巩固治疗期应至少12个月，但需要更多的数据来确定更长的合并期将降低复发的风险

GEN：怀孕妇女是否有新建议？

Terrault博士：乙型肝炎表面抗原（HBsAg）阳性孕妇的HBV DNA水平大于200,000 IU / mL，以防止围产期传播被推荐使用。替诺福韦是孕妇研究的三种首选疗法 - 聚乙二醇干扰素，恩替卡韦和替诺福韦之中唯一的药物，大多数研究已经在28至32周的妊娠期开始治疗。
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GEN：HBsAg损失的患者怎么样？

Terrault博士：HBsAg损失是治疗的理想目标，但很少实现，特别是在NAs方面。指南建议治疗可以在HBeAg损失后停止，但有证据表明治疗可以强烈推荐。再次，这是一种治疗方法，临床医生和患者之间就有关停药的风险和益处进行讨论是有必要的。值得注意的是，在肝硬化患者中不推荐停止治疗。如果治疗停止，复发的监测是至关重要的。监测ALT耀斑，复发性病毒血症和临床失代偿的患者应每三个月进行一次治疗至少一年。

GEN：哪些慢性HBV患者应该长期治疗

Terrault博士：正如具体评论所强调的那样，一般推荐对慢性HBV肝硬化患者进行无限期抗病毒治疗，因为与病毒学复发失代偿有关。任何HBsAg阳性的成人与HBeAg代谢异常组合，ALT水平或HBV DNA水平相关，治疗也应继续。

GEN：假设HBV治疗耐受良好，成本不是问题，不是无限期地将所有可检测HBV的患者保持治疗的最佳策略是？

Terrault博士：在所有慢性HBV患者中使用无限疗法的主要观点是，并非所有患者都需要进行治疗以尽量减少肝脏相关并发症的风险。在我们进行治疗治疗之前，我们的治疗目标是确定治疗提供有益的治疗目标，并在需要的时候继续治疗。对于一些患者，治疗可能是无限期的，但对于其他患者，治疗过程减少将达到预期的终点。即使治疗耐受性好，另一个反对无限期治疗的观点也是依从性。

GEN：HBV治疗指南中未来修改的可能性有哪些？

Terrault博士：HBV治疗正在发展，所以我预计未来对HBV治疗指南的修改将是必要的。此外，有关抗病毒治疗效果的自然史队列研究的更多数据可能会导致有关何时开始和何时停止治疗的建议更改。最后，在特殊人群中有一些方面的HBV管理，如与丙型肝炎病毒或艾滋病毒感染的那些人，将在今后的指导性文件中得到解决。

由Ted Bosworth编译

咬牙硬挺

变化不大，期待突破