Antiviral effect of entecavir in chronic hepatitis B patients with rtA181V/T mutation
DOI:10.3969/j.issn.1001-5256.2021.05.016
- VernacularTitle:恩替卡韦对rtA181V/T突变的慢性乙型肝炎患者的抗病毒效果观察
- Author:
Shuqin LI
1
;
Jing ZHOU
;
Yuan GAO
;
Xiaoyan MA
;
Liping WANG
Author Information
1. Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
- Publication Type:Research Article
- Keywords:
Hepatitis B, Chronic;
Entecavir;
Mutation;
Therapeutics
- From:
Journal of Clinical Hepatology
2021;37(5):1053-1058.
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the clinical effect of entecavir (ETV) rescue treatment in chronic hepatitis B (CHB) patients at the onset of rtA181V/T mutation. MethodsA total of 174 CHB patients who were treated in the outpatient and inpatient departments of The Affiliated Hospital of Xuzhou Medical University from January 2012 to January 2017 and underwent the detection of drug-resistance mutations of the genes in the reverse transcription (RT) polymerase region were enrolled, among whom there were 72 previously untreated patients and 102 treatment-experienced patients with virological breakthrough or poor response. The association between the previous medication history of nucleos(t)ide analogues and the mutation pattern (including rtA181V/T) was evaluated in the treatment-experienced CHB patients. A total of 155 patients were enrolled, among whom 72 patients had no drug-resistance mutations, 45 had rtA181V/T mutation, and 38 had rtA181V/T+rtN236T mutation. The three groups were compared in terms of virologic response and biochemical parameters at baseline and at weeks 24 and 48 of ETV rescue treatment. The t-test was used for comparison of normally distributed continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups; the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between two groups. A logistic regression analysis was used to screen out the influencing factors for poor prognosis. ResultsA analysis of the previous medication history of NAs and the mutation patterns for all patients suggested that the patients with the medication history of multiple NAs tended to have multisite mutations and multi-drug resistance (χ2=4295, P＜0.05). The level of HBV DNA at the time of virological breakthrough was lower than that at the time of initial administration of NAs in the rtA181V/T mutation group ［(6.22±1.48) log10 IU/ml vs (7.08±1.59) log10 IU/ml, t=3.098, P=0.002］ and the rtA181V/T+rtN236T mutation group ［(5.94±1.45) log10 IU/ml vs (6.94±1.61) log10 IU/ml，t=2.850, P=0.004］. At week 48 of ETV rescue treatment, there were no significant differences between the three groups in HBV DNA negative conversion rate (83.3% vs 82.2% vs 81.6%, P＞0.05) and HBeAg negative conversion rate (22.2% vs 17.8% vs 21.1%, P＞0.05), and there were also no significant differences in alanine aminotransferase normalization rate (77.1% vs 85.2% vs 83.3%, P＞0.05), aspartate aminotransferase normalization rate (80.4% vs 75.9% vs 76.0%, P＞0.05), and total bilirubin normalization rate (80.8% vs 79.3% vs 78.1%, P＞0.05). HBV DNA level at the beginning of ETV treatment was the risk factor for the treatment outcome of 48-week antiviral therapy (odds ratio = 1.655, 95% confidence interval: 1.128-2.428, P=0.01). ConclusionETV has a good antiviral effect in treatment-experienced CHB patients with rtA181 drug-resistance mutation, and HBV DNA level at the initiation of ETV treatment can predict the outcome of 48-week ETV rescue treatment.
