拉米夫定耐药慢性乙型肝炎患者HBVP区基因突变模式与临床特征

目的分析慢性乙型肝炎患者在拉米夫定（LAM）治疗过程中出现耐药后，HBVP区基因突变模式及临床特征。方法对2009年4月～2009年12月在石家庄市第五医院就诊的116例临床诊断为LAM耐药慢性乙型肝炎患者进行HBVP区基因序列测定。结果116例临床诊断为LAM耐药患者血清HBVDNA水平为（5．34±1．21）log10拷贝／mL，ALT为（135±89）U／L，60．7％（70／116）的患者出现ALT升高。116例患者均出现基因耐药突变，共有7种突变模式，94．8％（110／116）发生YMDD基序突变，其中单纯YMDD突变占22．4％（26／116），YMDD联合rtLl80M突变占72．4％（84／116），5．2％（6／116）发生单纯rtLl80M突变。rtM204V联合rtLl80M突变的发生率为87．5％（56／64），rtM204I联合rtLl80M突变的发生率为69．4％（50／72），差异有显著统计学意义（P=0．04）。LAM耐药时，4种突变类型即rtM204I、rtLl80M＋rtM204V、rtLl80M＋rtM2041和rtLl80M＋r[IⅥ204V／I患者血清HBeAg、HBVDNA、ALT水平之间差异无统计学意义，P值分别为0．63，O．72，0．82。结论YMDD基序突变是LAM耐药后HBVP区基因突变的主要模式，rtM204V多以联合rtLl80M突变的形式存在，LAM耐药后患者肝组织损伤程度以及病毒复制水平可能与HBVP区突变类型无关。

The mutation patterns of HBV P gene and clinical features in patients with lamivudine-resistant chronic hepatitis B

Objective To analyze the mutation patterns of HBV P gene and clinical features in patients with chronic hepatitis B （CHB） after the emergence of drug-resistance during lamivudine （LAM） therapy. Methods LAM-resistant mutations were detected by sequencing the HBV P gene in patients with LAM- resistant CHB in the fifth hospital of Shijiazhuang from Apr. 2009 to Dec. 2009. Results In 116 LAM-resistant patients with CHB, the mean value of serum HBV DNA was （5.34 ± 1.21） log10 copies/mL, the mean value of alanine aminotransferase （ALT） was （135± 89） U/L. The rate of ALT elevation was 60.7%（70/116）. All the 116 patients had HBV gene mutations. There were 7 mutation patterns. YMDD mutations happened in 94.8% （110/116） patients. Only YMDD mutation, YMDD combined with rtL 180M mutation was 22.4%（26/116） and 72.4%（84/116）, respectively, rtL 180M mutation happened in 5.2%（6/116） patients. The rate of rtM204V combined with rtL180M mutation or rtM204I combined with rtL180M mutation was 87.5%（56/64） and 69.4%（50/72）, respectively（P=0.04）. There were no significant difference between the mutation mentioned above and the positive rate of HBeAg or the levels of the serum HBV DNA and the ALT of patients. Conclusion YMDD- motif mutation is the major mutation pattern of HBV P gene after emergence of LAM-resistance. Compared with rtM204I mutation, rtM204V mutation is more combined with rtL180M mutation. The mutation patterns of HBV P gene have no relationship with HBV replication and the severity of liver tissue injury.