Hepatitis flares and hepatitis B e antigen seroconversion: Implication in anti-hepatitis B virus therapy
Hepatitis flares and hepatitis B e antigen seroconversion: Implication in anti-hepatitis B virus therapy
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DOI：
10.1046/j.1440-1746.2003.02976.x
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发表时间：
2003-03-01
影响因子：
4.1
通讯作者：
Liaw, YF
中科院分区：
文献类型：
--
作者：
Liaw, YF
慢性乙型肝炎病毒(HBV)感染的急性加重或急性加重，定义为血清丙氨酸氨基转移酶(ALT)突然升高超过正常上限(ULN)的五倍，是人类白细胞抗原-I(HLA-I)限制性的细胞毒性T淋巴细胞(CTL)介导的针对乙肝病毒的免疫反应及其下游机制的结果。较高的ALT水平反映了更强烈的免疫反应和更广泛的肝溶解，在极端情况下，可能会导致失代偿和衰竭。相反，在自然病程和药物治疗的情况下，较高的ALT也反映了更强大的乙肝免疫清除能力，因此，无论是在自然病程还是药物治疗中，HBVDNA丢失和乙肝e抗原(HBeAg)血清转换的可能性都更高。丙氨酸氨基转移酶的5倍ULN似乎是一个显着的分界值，从内源性免疫应答的角度对患者进行分类。ALT水平低于ULN的五倍或免疫反应不太强烈的患者需要免疫调节来诱导强大的免疫反应，以增强乙肝病毒的清除。相反，免疫反应较强或ALT暴发超过ULN 5倍的患者应密切监测自发性乙肝病毒清除/HBeAg血清转换情况，或及时开始直接抗病毒治疗，以防止肝功能失代偿的发生或恶化。总之，更好地了解肝炎暴发的发病机制和自然病程，更明智地选择患者和药物治疗的时机是取得更好治疗效果的关键。(C)2003年Blackwell出版亚洲私人有限公司。
Hepatitis flares or acute exacerbations, defined as an abrupt elevation of serum alanine aminotransferase (ALT) over fivefold the upper limit of normal (ULN), of chronic hepatitis B virus (HBV) infection are the results of HLA-I restricted, cytotoxic T lymphocyte (CTL)-mediated immune response against HBV and its downstream mechanisms. Higher ALT levels reflect a more vigorous immune response and a more extensive hepatolysis that, in the extreme situation, may lead to decompensation and failure. In contrast, higher ALT also reflects a more robust immune clearance of HBV and, therefore, a higher chance of HBV-DNA loss and hepatitis B e antigen (HBeAg) seroconversion, both in the setting of natural course and drug therapy. Alanine aminotransferase of fivefold the ULN appears to be a significant cut-off level to categorize the patients in terms of endogenous immune response against HBV. Patients with ALT levels less than fivefold the ULN or those with a less vigorous immune response require immunomodulation to induce robust immune response to enhance HBV clearance. In contrast, those with a more vigorous immune response or those with ALT flare over fivefold the ULN should be monitored closely for spontaneous HBV clearance/HBeAg seroconversion or to start direct antiviral therapy in time to prevent the occurrence or deterioration of hepatic decompensation. In conclusion, a better understanding of the pathogenetic mechanisms and natural course of hepatitis flares, wiser selection of patients and the timing of drug therapy are crucial to achieve better treatment results. (C) 2003 Blackwell Publishing Asia Pty Ltd.