目的 采用干扰素和阿德福韦酯治疗慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，比较两种治疗策略的临床疗效。 方法 选择2002年2月-年12月经100 mg拉米夫定治疗后出现YMDD变异的慢性乙型肝炎患者76例。其中，男52例，女24例；年龄18~55岁，平均年龄33岁。服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA低于治疗前水平，丙氨酸转移酶(alanine aminotransferase，ALT)lt;2×ULN/L患者分为A组(26例)，继续用100 mg拉米夫定治疗48周；服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA定量检测高于或等于治疗前水平，ALTgt;2×ULN/L，根据患者自愿分为B组(27例)和C组(23例)。B组用100 mg拉米夫定联合10 mg阿德福韦酯治疗48周；C组用干扰素治疗48周。分别观察3组ALT复常率及HBV DNA转阴率、HBeAg阳性患者血清学转换率。 结果 治疗48周时，B、C组患者ALT复常率分别是74.1%和78.3%，明显高于A组的34.6%，差异有统计学意义(Plt;0.05)；B、C组患者HBV DNA转阴率分别是77.7%和73.9%，明显高于A组的11.5%，差异有统计学意义(Plt;0.05)；3组HBeAg阳性患者血清学转换率比较，差异均无统计学意义(Pgt;0.05)。 结论 慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，继续用拉米夫定治疗疗效不理想，改用干扰素或联合阿德福韦酯治疗更安全有效。
ObjectiveTo investigate the correlation of spontaneous YMDD mutation in different hepatitis B virus (HBV) genotypes with HBV-related hepatocellular carcinoma (HCC). MethodFrom May 2010 to May 2012, 110 HBV-related hepatocellular cancer patients not treated by anti-virus drugs and 1 079 chronic HBV infectors (including asymptomatic HBV carriers, chronic hepatitis B patients, and HBV-related liver cirrhosis patients) were included in our study. HBV YMDD mutation was detected by fluorescence hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using Diagnosis Kit for HBV YMDD Mutation (Qiagen Biotechnology). Serum HBV genotype was detected by real time PCR using genotype specific TaqMan probe. According to data type, t-test, χ2-test and unconditional logistic regression were used for statistical analysis. ResultsIn the HCC group, genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 39 patients (35.5%), 16 patients (14.5%) and 14 patients (12.7%), respectively. In the chronic HBV infection group, HBV genotype C virus, spontaneous YMDD mutation and genotype C virus with YMDD mutation were detected in 153 patients (14.2%), 46 patients (4.3%) and 17 patients (1.6%), respectively. The difference between the two groups were statistically significant (χ2=33.368, P<0.001; χ2=21.353, P<0.001; χ2=48.889, P<0.001). Unconditional logistic regression analysis suggested that infection of genotype C virus and genotype C virus with spontaneous YMDD mutation might be important risk factors for the development of HCC[OR=2.943, 95%CI (1.778, 4.872), P<0.001; OR=5.989, 95%CI (2.394, 14.980), P<0.001]. ConclusionsInfection of genotype C virus with spontaneous YMDD mutation is tightly related with the occurrence of HCC and has important value for earlier warning of HCC.