慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析*

doi:10.3969/j.issn.1672-5069.2019.01.012

摘要/Abstract

摘要： 目的探讨慢性乙型肝炎（CHB）患者HBV基因型及其耐药突变发生情况。方法纳入240例接受核苷（酸）类似物单药或联合或序贯治疗的CHB患者,采用PCR扩增HBV逆转录（RT）区和序列测定鉴定耐药基因突变,采用HBV S基因测序法鉴定基因型。结果在35例单用拉米夫定治疗的CHB患者中,发生耐药突变14例（40.0%）,突变位点为rtL80I/V、rtVl73L、rtLl80M、rtM204V/I和rtV207I,23例单用阿德福韦治疗者发生耐药突变11例（47.8%）,突变位点为rtAl81T/V、rtS213T/N、rtV214A、rtQ215S/H/P、rtl233V、rtN236T、rtP237H和rtN/H238A/K/D/S,70例单用恩替卡韦治疗者发生耐药突变10例（14.3%）,突变位点为rtM204I,12例单用替比夫定治疗者发生耐药突变5例（41.7%）,突变位点为rtI169T、rtL180M、rtT184G/S/A/I/L/F、rtS202I/G、rtM204V和rtM250V/I/L,100例接受联合或序贯治疗者发生耐药突变51例（51.0%）,突变位点为rtA194T,恩替卡韦治疗患者耐药突变发生率最低（P<0.05）;240例CHB患者中,HBV基因B型21例（8.8%）、C型216例（90.0）和D型3例（1.2%）;在发生耐药突变的91例患者中,B型6例（6.6%）、C型83例（91.2%）和D型2例（2.2%,x²=1.22,P>0.05）;在发生耐药突变的6例B型感染者中有2例（33.3%）和83例C型感染者中有15例（18.1%）发生了多重耐药突变。结论检测CHB患者感染HBV基因型并及时获得耐药突变基因分布,将有助于指导临床治疗。

关键词: 慢性乙型肝炎, 核苷（酸）类似物, HBV基因型, 耐药突变

Abstract: Objective To investigate the distribution of HBV genotypes and drug-resistant mutations in patients with chronic hepatitis B（CHB）. Methods 240 patients with CHB receiving monotherapy or swift from one to another of nuleos（t）ide analogues（NAs） for at least three months were recruited in this study,and the drug resistance mutation was assayed by sequencing reverse transcription area and the HBV genotypes were detected by sequencing HBV S gene. Results The resistant mutation rate in 35 patients treated by lamivudine was 40.0% with the resistant mutation sites of rtL80I/V,rtVl73L,rtLl80M,rtM204V/I,and rtV207I;the resistant mutation rate in 23 patients receiving adefovir was 47.8% with the mutation sites of rtAl81T/V,rtS213T/N, rtV214A,rtQ215S/H/P,rtl233V,rtN236T,rtP237H,rtN/H238A/K/D/S;the mutation rate in 70 receiving entecavir was 14.3% with the mutation sites of rtM204I;the resistant mutation rate in 12 patients receiving telbivudine 41.7% with the mutation sites of rtI169T,rtL180M,rtT184G/S/A/I/L/F,rtS202I/G,rtM204V and rtM250V/I/L;the resistance mutation rate in 100 patients with combination or swift therapy was 51.0% with the mutation sites of rtA194T;out of 240 patients with CHB,21（8.8%） were with type B,216（90.0%） were with type C,and 3 （1.2%） were with type D hepatitis B viral infection;out of the 91 patients with drug resistance mutations,6 （6.6%） were with type B,83（91.2%） were with type C,and 2（2.2%） were with type D infection;multidrug resistance mutations occurred in 2 （33.3%） of 6 patients with type B and 15（18.1%） of 83 type C infection. Conclusion Surveillance of HBV genotypes and resistance mutations in patients with CHB receiving NAs therapy might help improve the clinical response.

Key words: Hepatitis B, Nuleos（t）ide analogues, HBV genotypes, Drug resistance mutations

张欢欢, 杨欢, 沈思兰, 陈佳婕, 宣彬彬. 慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析^*[J]. 实用肝脏病杂志, 2019, 22(1): 41-44.

Zhang Huanhuan, Yang Huan, Shen Silan, et al.. Distribution of HBV genotypes and drug-resistant mutations in patients with chronic hepatitis B[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 41-44.

参考文献

[1] Biondo MI,Germano V,Pietrosanti M,et al.Lack of hepatitis B virus reactivation after anti-tumour necrosis factor treatment in potential occult carriers with chronic inflammatory arthropathies. Eur J Intern Med,2014,25(5):482-484.
[2] Sibnarayan Datta SCVV.Recent advances in molecular diagnostics of hepatitis B virus. World J Gastroenterol,2014,20(40):14615-14619.
[3] Biondo MI,Germano V,Pietrosanti M,et al.Lack of hepatitis B virus reactivation after anti-tumour necrosis factor treatment in potential occult carriers with chronic inflammatory arthropathies. Eur J Intern Med,2014,25(5):482-484.
[4] Monjezi R,Tan SW,Tey BT,et al.Detection of hepatitis B virus core antigen by phage display mediated TaqMan real-time immuno-PCR. J Virol Methods,2013,187(1):121-126.
[5] Jaramillo CM,De FLH,Porras A,et al.Characterization of hepatitis B virus in Amerindian children and mothers from Amazonas State,Colombia. Plos One,2017,12(10):1816-1823.
[6] Apiung T,Ndanu TA,Mingle JA,et al.Hepatitis B virus surface antigen and antibody markers in children at a major paediatric hospital after the pentavalent DTP-HBV-HIV vaccination. J Intens Care Med,2017,51(1):13-18.
[7] Pfefferkorn M,Böhm S,Schott T,et al.Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers. Gut,2017,31(16):31-38.
[8] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅩⅢ.
[9] Blanch L,Sales B,Montanya J,et al.Validation of the Better Care,system to detect ineffective efforts during expiration in mechanically ventilated patients:a pilot study. J Intens Care Med,2012,38(5):772-780.
[10] Alidjinou EK,Michel C,Canva V,et al.Very slow decline of hepatitis B virus surface antigen and core related antigen in chronic hepatitis B patients successfully treated with nucleos(t)ide analogues. J Med Virol,2018,13(21):2469-2475.
[11] 马勇. 乙型肝炎病毒携带孕妇乳汁和血清HBV DNA载量与婴儿感染率的关系分析. 实用肝脏病杂志,2017,20(4):486-487.
[12] Han W,Ni Q,Liu K,et al.Decreased CD122 on CD56 dim,NK associated with its impairment in asymptomatic chronic HBV carriers with high levels of HBV DNA,HBsAg and HBeAg. Life Sci,2018,22(8):53-60.
[13] Fuchino M,Tajiri K,Minemura M,et al.Vanishing tumor in a liver graft from a hepatitis B virus surface antigen-positive donor. J Intens Care Med,2017,11(3):610-615.
[14] 陈成伟,陈从新,陈士俊,等. 核苷和核苷酸类药物治疗CHB的耐药及其管理. 中国实用内科杂志,2013,33(1):82-91.
[15] Simonetti G,Gitto S,Golfieri L,et al.Quality of life of hepatitis B virus surface antigen-positive patients with suppressed viral replication:comparison between inactive carriers and nucleot(s)ide analog-treated patients. Eur J Gastroenterol Hepatol,2018,16(3):1983-1987.
[16] Huang R,Wang J,Hao Y,et al.The potential risk of HBV reactivation in patients with resolved HBV infection during direct-acting antiviral therapy. Aliment Pharmacol Ther,2017,46(7):702-707.
[17] Morsica G,Bagaglio S,Spagnuolo V,et al.Immune response to hepatitis B vaccination in HIV-positive individuals with isolated antibodies against hepatitis B core antigen:Results of a prospective Italian study. Plos One,2015,62(9):536-537.
[18] Bui TTT,Tan TT,Nghiem MN,et al.Molecular characterization of hepatitis B virus in Vietnam. BMC Infect Dis,2017,17(1):601-609.
[19] Benyakov G,Devika K,Etzion O,et al.A misleading pattern of serologic findings during hepatitis B virus infection. Ann Intern Med,2017,167(8):476-482.
[20] Chernet A,Yesuf A,Alagaw A.Seroprevalence of hepatitis B virus surface antigen and factors associated among pregnant women in Dawuro zone,SNNPR,Southwest Ethiopia:a cross sectional study. BMC Res Notes,2017,10(1):418-423.

慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析^*

Distribution of HBV genotypes and drug-resistant mutations in patients with chronic hepatitis B

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