Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.
Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.
复制标题
血清ALT和T细胞受体β可变链对慢性乙型肝炎患者替诺福韦治疗期间HBeAg血清转换的预测价值
DOI：
10.1097/md.0000000000006242
复制
发表时间：
2017-03
期刊：
影响因子：
1.6
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Yang J;Yan D;Guo R;Chen J;Li Y;Fan J;Fu X;Yao X;Diao H;Li L
摘要有效的抗病毒治疗是延缓慢性乙型肝炎(CHB)进展的关键。确定血清指标，包括乙肝e抗原(HBeAg)的表达和血清转换，将有助于评估HBeAg阳性CHB患者的抗病毒治疗效果。在富马酸替诺福韦(TDF)治疗96周期间，分别于基线和每12周检测32例患者的生化、血清学、病毒学指标和循环中CD4+CD25+调节性T细胞(Treg)的频率。分析乙肝病毒脱氧核糖核酸(DNA)与Treg和丙氨酸氨基转移酶(ALT)的关系。用基因熔融光谱技术测定T细胞受体β可变链(TRBV)的分子图谱。对于血清转换的12名患者，ALT在24周时下降到正常水平，并在随后的治疗中保持在这一水平；此外，24周时HBeAg血清转换(SC)的ALT预测截断值为41.5 U/L。在SC患者中，HBVDNA与Treg、ALT呈显著正相关，而在非SC患者中无相关性。6个TRBV家系(BV3、BV11、BV12、BV14、BV20和BV24)在基线时主要在SC患者中表达。丙氨酸氨基转移酶(ALT)下降可预测慢性乙肝患者TDF治疗期间HBeAg血清转阴率。此外，Tregs和TRBV的分布可能与HBeAg血清转换有关，也可以作为预测HBeAg SC和CHB患者治疗结果的潜在指标。
Abstract Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4+CD25+ regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients.