SIG计划提供HBV耀斑的更新 日期：2018年11月11日

StephenW

SIG Program Provides Update on HBV Flares
on: November 11, 2018
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Marc G. Ghany, MD, MHSc, FAASLD

Alanine aminotransferase (ALT) flares are a common feature of hepatitis B (HBV) and are a sensitive indicator of liver injury. Yet not all flares are injurious, according to speakers during the Hepatitis B Special Interest Group session on Sunday.

“There are good flares and bad flares,” said Marc G. Ghany, MD, MHSc, FAASLD, Clinical Tenure Track Investigator in the Liver Disease Branch of the National Institute of Diabetes and Digestive and Kidney Diseases. “But for now, we have no biomarkers to tell us whether any particular flare is good or bad.”

In patients with chronic HBV, ALT levels are used to trigger diagnostic testing, as a surrogate marker of disease severity, to monitor disease activity and progression, as a criterion to assess the need for treatment and as a treatment endpoint.

Flares are a part of the natural history of untreated HBV and chronic HVB, said Dr. Ghany. Flares are more frequent in patients who are older, male, Asian, HBeAg positive and infected with HBV genotype C. Expect flares during antiviral therapy, after the withdrawal of antiviral therapy, during or after immunosuppression or chemotherapy and post-partum, he said.

“Most flares resolve within two months,” Dr. Ghany said. “Virtually all should be resolved within six months.”

But what is a flare? Most definitions focus on abrupt or intermittent elevations in serum ALT. Dr. Ghany proposed a standardized definition as an abrupt elevation in serum ALT greater than five times the upper limit of normal and more than twice the patient’s baseline value.

Identifying a flare can be challenging, he added. Only about a third of flares produce clinical symptoms, usually acute hepatitis-like symptoms, hepatic decompensation with or without cirrhosis or death.

At the same time, ALT flares can be confused with a superinfection of other hepatotrophic viruses including hepatitis A, C, D and E, drug toxicity, alcoholic hepatitis and autoimmune hepatitis.

“You need to exclude all these other diagnoses,” Dr. Ghany cautioned.

Good flares can improve HBeAg seroconversion, and elevated ALT level is associated with higher levels of spontaneous HBeAg seroconversion. Bad flares can produce jaundice, lead to recurrent or multiple flares and sometimes both.

Patients should be monitored weekly or biweekly during a flare for clinical deterioration or hepatic decompensation, Dr. Ghany advised. Patients who are over 30, have stable or increasing HBV DNA or are HBeAg negative/anti-HBe positive may be candidates for early treatment.

“Patients with cirrhosis or decompensation should be treated immediately with a first line nucleoside analogue,” he added.

The mechanisms by which flares mediate liver damage are emerging, said Kyong-Mi Chang, MD, Professor and Associate Director of the Penn Center for Viral Hepatitis, University of Pennsylvania. ALT flares suppress both T-cells and B cells but upregulate NK activation. Cytokines produced during the flare promote NK-mediated liver damage via t TRAIL and TRAIL receptor pathways.

Flares associated with treatment also alter the NK phenotype, noted Dr. Chang. The altered phenotype is associated both with improved HBV-specific T-cell response and HBsAg loss. That suggests NK cells may regulate T-cell activity and predict the loss of HBsAg.

StephenW

SIG计划提供HBV耀斑的更新
日期：2018年11月11日
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Marc G. Ghany，医学博士，MHSc，FAASLD

丙氨酸氨基转移酶（ALT）突发是乙型肝炎（HBV）的常见特征，是肝损伤的敏感指标。然而，周日乙肝特别兴趣小组会议上的发言人表示，并非所有的照明弹都是有害的。

“有明显的耀斑和不良耀斑，”Marc G. Ghany医学博士，MHSc，FAASLD，国家糖尿病和消化和肾脏疾病研究所肝病科临床终身研究员。 “但就目前而言，我们没有任何生物标记可以告诉我们是否有任何特定的耀斑是好还是坏。”

在患有慢性HBV的患者中，ALT水平用于触发诊断测试，作为疾病严重性的替代标志，以监测疾病活动和进展，作为评估治疗需求和作为治疗终点的标准。

Ghany博士说，耀斑是未经治疗的HBV和慢性HVB的自然史的一部分。对于年龄较大，男性，亚洲人，HBeAg阳性并且感染HBV基因型C的患者，眩光更常见。在抗病毒治疗期间，抗病毒治疗后，免疫抑制期间或之后或产后期间，预计会出现眩光，他说。

“大多数耀斑在两个月内消退，”加尼博士说。 “几乎所有人都应该在六个月内解决。”

但是什么是耀斑？大多数定义集中于血清ALT的突然或间歇性升高。 Ghany博士提出了一个标准化的定义，即血清ALT突然升高超过正常上限的五倍，超过患者基线值的两倍。

他补充说，识别闪光可能具有挑战性。只有大约三分之一的突发出现临床症状，通常是急性肝炎样症状，伴有或不伴有肝硬化或死亡的肝功能失代偿。

同时，ALT突发可能与其他肝细胞病毒的重复感染混淆，包括甲型，丙型，丁型和戊型肝炎，药物毒性，酒精性肝炎和自身免疫性肝炎。

“你需要排除所有这些其他诊断，”加尼博士警告说。

良好的突发可以改善HBeAg血清转换，ALT水平升高与自发性HBeAg血清转换水平升高有关。不良耀斑会导致黄疸，导致反复发作或多发突发，有时两者兼而有之。

Ghany博士建议，患者应在每次或每两周一次的临床恶化或肝功能失代偿期间进行监测。 30岁以上，HBV DNA稳定或增加或HBeAg阴性/抗HBe阳性的患者可能是早期治疗的候选者。

“患有肝硬化或失代偿的患者应立即用一线核苷类似物治疗，”他补充说。

宾夕法尼亚大学宾夕法尼亚大学病毒性肝炎中心教授兼副主任Kyong-Mi Chang医学博士说，正在出现耀斑介导肝损伤的机制。 ALT突发抑制T细胞和B细胞，但上调NK活化。在突发期间产生的细胞因子通过TRAIL和TRAIL受体途径促进NK介导的肝损伤。

张博士指出，与治疗相关的突发也会改变NK表型。改变的表型与改善的HBV特异性T细胞应答和HBsAg消失相关。这表明NK细胞可能调节T细胞活性并预测HBsAg的丢失。