乙型肝炎病毒RNA作为安全停用抗病毒药物的生物标志物：核苷（酸）类似物停药的前瞻性研究
Hepatitis B Virus RNA as a Biomarker for Safe Antiviral Discontinuation: A Prospective Study of Nucleos(t)ide Analogue Withdrawal.
作者信息
Terrault Norah A, Sterling Richard, Lok Anna S, Ghany Marc G, Feld Jordan J, Cloherty Gavin, Wahed Abdus S, Yang Xue
机构信息
Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles.
Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond.
出版信息
J Infect Dis. 2025 Jun 2;231(5):1290-1298. doi: 10.1093/infdis/jiae541.
BACKGROUND
Withdrawal of nucleos(t)ide analogue therapy is associated with hepatitis B surface antigen (HBsAg) loss and sustained off-therapy partial cure (normal alanine aminotransferase [ALT] ≤30 U/L for males and ≤20 U/L for females with hepatitis B virus [HBV] DNA <2000 IU/mL) but should be offered only to those most likely to benefit. HBV RNA may be useful for risk stratification.
METHODS
The Hepatitis B Research Network Immune-Active Trial prospectively evaluated treatment with tenofovir disoproxil fumarate (TDF) for 192 weeks ± peginterferon alfa-2a for the initial 24 weeks, followed by protocolized withdrawal of TDF among eligible participants (ClinicalTrials.gov NCT01369212). HBV RNA was evaluated as a predictor of ALT flares and sustained partial cure (HBV DNA <2000 IU/mL) 48 weeks after TDF withdrawal.
RESULTS
Of 93 participants discontinuing TDF (n = 52, TDF + peginterferon alfa-2a; n = 41, TDF alone), 52 (55.9%) had unquantifiable HBV RNA at end of treatment. ALT flares >5 times the upper limit of normal at 48 weeks off therapy occurred in 33.3%, with pretreatment age (≥35 years) and quantifiable HBV RNA at end of treatment the best predictors (area under the receiver operating characteristic curves, 0.74 and 0.85 for training and test sets, respectively). A total of 26 (28.3%) had sustained partial cure, 3 (11.5%) with ALT flare. Nonquantifiable HBV RNA and quantitative HBsAg <100 IU/mL at end of treatment were the best predictors of sustained partial cure (area under the receiver operating characteristic curves, 0.84 and 0.93 for training and test sets). If HBV RNA was quantifiable at end of treatment, the likelihood of sustained partial cure was only 3%, whereas if HBV RNA was unquantifiable and quantitative HBsAg was <100 IU/mL, this likelihood was 73%.
CONCLUSIONS
HBV RNA is a useful biomarker in predicting likelihood of achieving sustained partial cure and safe withdrawal of nucleos(t)ide analogues.
背景
核苷（酸）类似物治疗的停药与乙肝表面抗原（HBsAg）消失及停药后持续部分治愈（男性丙氨酸氨基转移酶[ALT]≤30 U/L，女性≤20 U/L，乙肝病毒[HBV] DNA<2000 IU/mL）相关，但仅应提供给最可能受益的患者。HBV RNA可能有助于风险分层。
方法
乙肝研究网络免疫活性试验前瞻性评估了富马酸替诺福韦二吡呋酯（TDF）治疗192周±最初24周联合聚乙二醇干扰素α-2a治疗，随后在符合条件的参与者中按照方案停用TDF（ClinicalTrials.gov NCT01369212）。评估HBV RNA作为TDF停药后48周ALT升高和持续部分治愈（HBV DNA<2000 IU/mL）的预测指标。
结果
在93名停用TDF的参与者中（n = 52，TDF+聚乙二醇干扰素α-2a；n = 41，仅TDF），52名（55.9%）在治疗结束时HBV RNA不可测。停药48周时ALT升高超过正常上限5倍的发生率为33.3%，治疗前年龄（≥35岁）和治疗结束时可测的HBV RNA是最佳预测指标（受试者工作特征曲线下面积，训练集和测试集分别为0.74和0.85）。共有26名（28.3%）实现了持续部分治愈，3名（11.5%）出现ALT升高。治疗结束时不可测的HBV RNA和定量HBsAg<100 IU/mL是持续部分治愈的最佳预测指标（受试者工作特征曲线下面积，训练集和测试集分别为0.84和0.93）。如果治疗结束时HBV RNA可测，持续部分治愈的可能性仅为3%，而如果HBV RNA不可测且定量HBsAg<100 IU/mL，此可能性为73%。
结论
HBV RNA是预测实现持续部分治愈及安全停用核苷（酸）类似物可能性的有用生物标志物。
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