Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA 94304, USA.
Aliment Pharmacol Ther. 2009 Dec 1;30(11-12):1150-8. doi: 10.1111/j.1365-2036.2009.04151.x. Epub 2009 Sep 24.
One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti-viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti-viral agents. Pre-existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes.
To determine the prevalence of hepatitis B DNA polymerase mutations in treatment-naïve patients.
We used a direct PCR sequencing test to detect DNA polymerase mutations in 472 consecutive treatment-naïve patients at two community gastroenterology clinics in Northern California.
A majority of patients were Asians (>95%), had either genotype B or C (95%) and had no evidence of cirrhosis or liver cancer (94%). Mean age was 45 +/- 13 and mean hepatitis B virus DNA was 5.3 +/- 1.8 log(10) IU/mL. Most patients did not have any detectable mutations (82.4%). Some (16.7%) had mutations of unknown clinical significance (rtV207M/L/I) and only 4 patients had rtA181A/S, rtA194S or M250I.
No rtM204V/I or rtN236T mutations were observed in our study. Less than 1% of our patients had mutations that can be associated with primary resistance to existing anti-viral therapies for hepatitis B virus.
核苷（酸）类似物治疗慢性乙型肝炎失败的最重要因素之一是抗病毒耐药性。原发性耐药是指乙型肝炎病毒聚合酶/逆转录酶（rt）中的氨基酸变化，导致对抗病毒药物的敏感性降低。未经治疗的患者可能会出现预先存在的耐药性突变，这可能会影响他们的治疗结果。
确定初治患者乙型肝炎 DNA 聚合酶突变的流行率。
我们使用直接 PCR 测序试验在加利福尼亚州北部的两个社区胃肠病学诊所的 472 例连续初治患者中检测 DNA 聚合酶突变。
大多数患者为亚洲人（>95%），具有 B 型或 C 型基因型（95%），无肝硬化或肝癌证据（94%）。平均年龄为 45 +/- 13 岁，平均乙型肝炎病毒 DNA 为 5.3 +/- 1.8 log(10) IU/mL。大多数患者没有检测到任何突变（82.4%）。一些患者（16.7%）有未知临床意义的突变（rtV207M/L/I），只有 4 例患者有 rtA181A/S、rtA194S 或 M250I。
我们的研究中未观察到 rtM204V/I 或 rtN236T 突变。我们的患者中不到 1%的患者存在与现有乙型肝炎病毒抗病毒治疗原发性耐药相关的突变。
