乙型肝炎患者核苷酸逆转录酶抑制剂治疗结果的预测因子

StephenW

Predictors of Therapeutic Outcome to Nucleotide Reverse Transcriptase Inhibitor in Hepatitis B Patients
Muneba Aziz
, Hafsa Aziz
, Yasir Waheed
, and Muzaffar Latif Gill
Published Online:4 Oct 2018https://doi.org/10.1089/vim.2018.0022

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Abstract

Hepatitis B is a clinically important public health issue. Infection leads to hepatocellular carcinoma. Therefore, patients need antiviral therapy for prolonged period to prevent the complication of the disease. Data concerning chronic hepatitis B (CHB) patients with high hepatitis B virus (HBV) DNA are limited. The aim of the study was to check the efficacy of the nucleoside reverse transcriptase inhibitors (tenofovir) in terms of suppression of HBV DNA. The secondary end point in the study is to evaluate trends of predictive variables that predict outcome of treatment. In this specific study, we evaluated 140 CHB male and female patients, of these 110 completed 48 weeks of treatment. On the basis of hepatitis B e antigen (HBeAg), patients were stratified; HBV DNA and hepatitis B surface antigen (HBsAg) levels were measured along with liver function tests. All enrolled patients were given tenofovir disoproxil fumarate 300 mg daily before breakfast. Overall, 69.1% of patients showed virologic response. HBeAg-negative patient group showed 68% viral suppression and HBeAg-positive patient group showed 45.9% over 24 months of treatment, while at 48 months it was shown to be 76.7% and 54.1%, respectively. None of the patients suffered HBsAg loss during the 48 months. Baseline high HBV DNA level was found as a significant predictor of response (OR, 1.9; 95% CI = 1.23–3.9, p = 0.005). None of the patients observed had serious adverse events. Mutations in the RT region of polymerase gene are shown to be associated with resistance to antiviral drugs. Among patients suffering with chronic HBV infection, HBeAg-negative patient group have better virologic response as compared with HBeAg-positive group. Higher concentration of HBV DNA at baseline has negative prediction for sustained viral suppression. The A-B motif interdomain rtL122F mutation was found in nonresponder patients in our study. Another mutation rtN248H observed in E motif considered to have effect on DNA primer grip, which forms part of binding pocket.
Conclusion

Patients with HBeAg-negative profile show better virologic response than HBeAg-positive patients within the same time period. Higher concentration of HBV DNA at baseline has negative prediction for viral suppression. The A-B motif interdomain rtL122F mutation was found in nonresponder patients in our study. Another mutation rtN248H observed in E motif considered to have effect on DNA primer grip, which forms part of binding pocket.

StephenW

乙型肝炎患者核苷酸逆转录酶抑制剂治疗结果的预测因子
Muneba Aziz
，Hafsa Aziz
，Yasir Waheed
和Muzaffar Latif Gill
在线发布：2018年10月4日https://doi.org/10.1089/vim.2018.0022

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抽象

乙型肝炎是临床上重要的公共卫生问题。感染导致肝细胞癌。因此，患者需要长期抗病毒治疗以预防疾病的并发症。关于患有高乙型肝炎病毒（HBV）DNA的慢性乙型肝炎（CHB）患者的数据是有限的。该研究的目的是检查核苷逆转录酶抑制剂（替诺福韦）在抑制HBV DNA方面的功效。该研究的次要终点是评估预测治疗结果的预测变量的趋势。在这项特定的研究中，我们评估了140名CHB男性和女性患者，其中110名患者完成了48周的治疗。在乙型肝炎e抗原（HBeAg）的基础上，对患者进行分层;测量HBV DNA和乙型肝炎表面抗原（HBsAg）水平以及肝功能测试。所有登记的患者在早餐前每天给予替诺福韦地索普西富马酸盐300mg。总体而言，69.1％的患者表现出病毒学应答。 HBeAg阴性患者组病毒抑制率为68％，HBeAg阳性患者组在治疗24个月后显示为45.9％，而48个月时分别为76.7％和54.1％。在48个月内，没有患者遭受HBsAg损失。发现基线高HBV DNA水平是反应的显着预测因子（OR，1.9; 95％CI = 1.23-3.9，p = 0.005）。观察到的患者均未发生严重不良事件。聚合酶基因的RT区域的突变显示与抗病毒药物的抗性相关。在患有慢性HBV感染的患者中，HBeAg阴性患者组与HBeAg阳性组相比具有更好的病毒学应答。基线时较高浓度的HBV DNA对持续病毒抑制具有阴性预测。在我们的研究中，在无应答患者中发现了A-B基序域间rtL122F突变。在E基序中观察到的另一个突变rtN248H被认为对DNA引物夹具有影响，其形成结合口袋的一部分。
结论

HBeAg阴性患者在同一时期内表现出比HBeAg阳性患者更好的病毒学应答。基线时较高浓度的HBV DNA对病毒抑制具有阴性预测。在我们的研究中，在无应答患者中发现了A-B基序域间rtL122F突变。在E基序中观察到的另一个突变rtN248H被认为对DNA引物夹具具有影响，其对于结合口袋的一部分。

StephenW

https://www.liebertpub.com/doi/1 ... &mcid=558087280