CAJ | 학술논문

目的分析应用核苷(酸)类药物(NA)治疗慢性乙型肝炎(CHB)患者耐药基因突变发生的危险因素和突变模式.方法选取本院经NA治疗的209例CHB患者,采用直接测序法检测患者血清标本中的HBV基因分型及耐药位点,并对结果进行分析,对可能影响HBV逆转录酶(RT)区耐药基因突变的危险因素,包括年龄、性别、基因型、HBeAg状态、HBV DNA水平、HBsAg阳性时间、家族史、病期、核苷(酸)类药物选择以及用药时间等进行统计分析,筛选出独立危险因素.结果年龄、基因型、NA药物选择及用药时间与HBV RT区耐药基因突变发生相关.209例患者测序结果中86例发现有耐药基因突变,突变率为41.15%,B型和C型基因患者耐药突变率分别33.67%和47.75%,差异具有统计学意义(χ2= 4.25,P< 0.05),但Logistic回归分析表明基因型不是HBV耐药基因突变发生的独立危险因素.HBV RT区突变以rtM204V/I(79.1%)、rtA181V/T/A/S(19.8%)和rtN236T(11.6%)突变株为主,rtM204V位点变异大多伴随了rtL180M突变.结论年龄大于45岁、曾使用LAM或LDT进行长时间治疗的CHB人群更容易导致HBV突变的发生,在使用NA治疗慢性乙型肝炎患者过程中,出现的变异模式复杂多样,应及时监测患者耐药基因以指导临床用药.
목적 분석응용핵감(산)류약물(NA)치료만성을형간염(CHB)환자내약기인돌변발생적위험인소화돌변모식.방법 선취본원경NA치료적209례CHB환자,채용직접측서법검측환자혈청표본중적HBV기인분형급내약위점,병대결과진행분석,대가능영향HBV역전록매(RT)구내약기인돌변적위험인소,포괄년령、성별、기인형、HBeAg상태、HBV DNA수평、HBsAg양성시간、가족사、병기、핵감(산)류약물선택이급용약시간등진행통계분석,사선출독립위험인소.결과 년령、기인형、NA약물선택급용약시간여HBV RT구내약기인돌변발생상관.209례환자측서결과중86례발현유내약기인돌변,돌변솔위41.15%,B형화C형기인환자내약돌변솔분별33.67%화47.75%,차이구유통계학의의(χ2= 4.25,P< 0.05),단Logistic회귀분석표명기인형불시HBV내약기인돌변발생적독립위험인소.HBV RT구돌변이rtM204V/I(79.1%)、rtA181V/T/A/S(19.8%)화rtN236T(11.6%)돌변주위주,rtM204V위점변이대다반수료rtL180M돌변.결론 년령대우45세、증사용LAM혹LDT진행장시간치료적CHB인군경용역도치HBV돌변적발생,재사용NA치료만성을형간염환자과정중,출현적변이모식복잡다양,응급시감측환자내약기인이지도림상용약.
Objective To analyze the risk factors that affect gene mutations in HBV reverse transcriptase gene and the mutation patterns in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogue therapy.Methods Among the 209 patients with CHB treated with nucleos(t)ide analogue therapy, HBV reverse transcriptase gene was analyzed by a direct PCR sequencing assay. The factors including age, sex, genotype, HBeAg status, level of serum HBV DNA, course of diseases, HBsAg positive time, family history of CHB, drug of choice and therapeutic time were analyzed, respectively. Independent risk factors related to HBV gene mutation were screened by statistical software. The mutation patterns were proifled too. Results Statistical analysis showed that age, genotype, drug of choice and therapeutic time were correlated with viral mutations in HBV reverse transcriptase gene. However, genotype was not the independent risk factor related to HBV mutation in the Logistic regression analysis. Eighty six patients were detected to be drug resistant among 209 (41.15%) cases. The percentages of genotype B and C of drug resistant mutations were 33.67% and 47.75%, respectively, with signiifcant difference (χ2= 4.25,P < 0.05). The frequency of mutations on rtM204V/I (79.1%), rtA181V/T/A/S (19.8%) and rtN236T (11.6%) were major in this cohort. Compared with the rtM204I mutations, the rtM204V mutations were preferentially accompanied by the rtL180M mutations.Conclusions HBV drug resistant mutations occurred more frequently in over 45 years old CHB patients with lamivudine or telbivudine treatment experience for a long therapeutic time. The mutation patterns were complicated variable and the reverse transcriptase gene of HBV in patients with CHB should be monitored just in time for better curative effect of antiviral therapy.