Kaewdech Apichat, Tangkijvanich Pisit, Sripongpun Pimsiri, Witeerungrot Teepawit, Jandee Sawangpong, Tanaka Yasuhito, Piratvisuth Teerha
Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Liver Int. 2020 Dec;40(12):2961-2971. doi: 10.1111/liv.14606. Epub 2020 Aug 3.
BACKGROUND & AIMS: The safe discontinuation of nucleos(t)ide analogue therapy remains challenging in chronic hepatitis B. We investigated the potential role of quantitative hepatitis B surface antigen, hepatitis B core-related antigen and hepatitis B virus RNA at the end of treatment in predicting off-therapy relapse.
Patients who fulfilled the stopping criteria of the Asian Pacific Association for the Study of the Liver guideline were enrolled. Virological relapse was defined as hepatitis B virus DNA level greater than 2000 IU/mL, and clinical relapse was defined as virological relapse plus alanine aminotransferase level of more than twice the upper limit of normal.
Ninety-two patients participated. The combination of end-of-treatment hepatitis B core-related antigen and hepatitis B virus RNA levels was most predictive of clinical relapse. Multivariate analysis revealed that end-of-treatment hepatitis B core-related antigen and hepatitis B virus RNA were independently associated with clinical relapse. During follow-up, no patients with undetectable hepatitis B core-related antigen (<3.0 log U/mL) and hepatitis B virusRNA (<2.0 log copies/mL) at end of treatment developed clinical relapse, in comparison with 22.9% and 62.5% patients with detectable levels of one or both biomarkers respectively. End-of-treatment quantitative hepatitis B surface antigen was linked to a likelihood of hepatitis B surface antigen clearance.
The combined hepatitis B core-related antigen and hepatitis B virus RNA assays at end of treatment were highly predictive of subsequent clinical relapse. These novel biomarkers could potentially be used to identify patients who could safely discontinue nucleos(t)ide analogue therapy.
在慢性乙型肝炎中，安全停用核苷（酸）类似物治疗仍然具有挑战性。我们研究了治疗结束时定量乙型肝炎表面抗原、乙型肝炎核心相关抗原和乙型肝炎病毒RNA在预测治疗后复发中的潜在作用。
纳入符合亚太肝脏研究协会指南停药标准的患者。病毒学复发定义为乙型肝炎病毒DNA水平大于2000 IU/mL，临床复发定义为病毒学复发加丙氨酸氨基转移酶水平超过正常上限的两倍。
92例患者参与研究。治疗结束时乙型肝炎核心相关抗原和乙型肝炎病毒RNA水平的联合检测对临床复发的预测性最强。多变量分析显示，治疗结束时乙型肝炎核心相关抗原和乙型肝炎病毒RNA与临床复发独立相关。在随访期间，治疗结束时乙型肝炎核心相关抗原（<3.0 log U/mL）和乙型肝炎病毒RNA（<2.0 log拷贝/mL）检测不到的患者均未发生临床复发，相比之下，一种或两种生物标志物水平可检测到的患者分别为22.9%和62.5%。治疗结束时定量乙型肝炎表面抗原与乙型肝炎表面抗原清除的可能性相关。
治疗结束时联合检测乙型肝炎核心相关抗原和乙型肝炎病毒RNA对随后的临床复发具有高度预测性。这些新型生物标志物可能有助于识别能够安全停用核苷（酸）类似物治疗的患者。
