乙型肝炎病毒基因型亚型与抗病毒疗效关系的研究

Relationship between HBV genotypes/sub -genotypes of hepatitis B virus and antiviral therapy

目的：探讨乙型肝炎病毒（HBV）基因型亚型与核苷类似物抗病毒疗效的关系。方法收集159例慢性乙型肝炎（CHB）患者的临床资料，据患者病情给予阿德福韦酯（ADV）或恩替卡韦（ETV）抗病毒治疗。应用巢式聚合酶链反应检测患者的基因型及亚型。于治疗前、治疗24周及48周，分别检测 HBV DNA 定量、ALT 水平以及血清病毒学标志物。分析 HBV 不同基因型、亚型与 ADV 及 ETV 抗病毒疗效的关系。结果（1）159例样本中 B 基因型26例（16．4％），均为 Ba 亚型；C 基因型128例（80．5％），均为 C2亚型，Ba／C2混合亚型5例（3．1％），未检出其他基因型。（2）ADV 治疗24周时 Ba 亚型与 C2亚型的 ALT 复常率为66.7％与66．2％（χ2＝0．74），HBeAg 转阴率为27．3与23．1％（χ2＝0．10），HBV DNA 转阴率为33．3％与30.9％（χ2＝0．03），治疗48周时 Ba 亚型以及 C2亚型的 ALT 复常率为83．3％与82．4％（χ2＝0．01），HBeAg 转阴率为45．5与34．4％（χ2＝0．49），HBV DNA 转阴率为58．3％与48．5％（χ2＝0．39），差异均无统计学意义（均 P ＞0.05）。ETV 治疗24周时 Ba 亚型以及 C2亚型的 ALT 复常率为71．4％与69．6％（χ2＝0．02），HBeAg 转阴率为33．3％与30．8％（χ2＝0．03），HBV DNA 转阴率为42．9％与39．3％（χ2＝0．06），治疗48周时 Ba 亚型与 C2亚型的 ALT 复常率为85．7％与83．9％（χ2＝0．03），HBeAg 转阴率为50．0％与44．9％（χ2＝0.10），HBV DNA转阴率为71．4％与67．8％（χ2＝0．07），差异均无统计学意义（均 P ＞0．05）。结论山西地区慢性乙型肝炎患者的 HBV 基因型、亚型以 C 基因型及 C2亚型为主。ADV 及 ETV 抗病毒疗效与 HBV 基因型、亚型无关。

Objective To investigate the relationship between the genotype /sub -genotype and antiviral treatment.Methods The clinical data of 159 patients with chronic HBV infections were collected,who were treated by adefovir dipivoxil （10mg/d）or entecavir（0.5mg/d）according to the disease′s conditions.The genotypes and subtypes of hepatitis B virus were determined by Nested polymerase chain reaction（nt PCR）.The levels of serum HBVDNA replication,ALT levels and HBV serologic markers were detected pre or post -treatment 24 weeks, 48 weeks.Observed the relationship between the HBV genotypes/sub -genotypes and the antiviral efficacy of adefovir dipivoxil or entecavir treatment.Results After 24 weeks of adefovir dipivoxil therapy,ALT normalization rate of subgenotype Ba and subgenotype C2 was 66.7% vs 66.2%（χ2 =0.74,P 〉0.05）,HBeAg negative conversion rate of two subgenotypes was 27.3% vs 23.1%（χ2 =0.10,P 〉0.05）,HBVDNA negative conversion rate of two sub genotype Ba and subgenotype C2 was 33.3% vs 30.9%（χ2 =0.03,P 〉0.05）,respectively.After treatment for 48 weeks,ALT normalization rates of subgenotype Ba and subgenotype C2 were 83.3% vs 82.4%（χ2 =0.01,P 〉0.05）,HBeAg negative conversion rates of two subgenotypes were 45.5% vs 34.4%（χ2 =0.49,P 〉0.05 ）,HBVDNA negative conversion rates of two subgenotypes were 58.3% vs 48.5%（χ2 =0.39,P 〉0.05）.After 24 weeks of entecavir therapy, ALT normalization rates of subgenotype Ba and subgenotype C2 were 71.4% vs 69.6%（χ2 =0.02,P 〉0.05 ）, HBeAg negative conversion rates of two subgenotypes were 33.3% vs 30.8%（χ2 =0.03,P 〉0.05 ）,HBVDNA negative conversion rates of two subgenotypes were 42.9% vs 39.3%（χ2 =0.06,P 〉0.05 ）,respectively.After treatment for 48 weeks,ALT normali zation rates of subgenotype Ba and subgenotype C2 were 85.7% vs 83.9%（χ2 =0.03,P 〉0.05）,HBeAg negative conversion rates of two subgenotypes were 50.0% vs 44.9%（χ2 =0.10, P 〉0.05）,HBVDNA negative conversion rates of two subgenotypes were 71.4%vs 67.8%（χ2 =0.07,P 〉0.05）. Conclusion The study showed that genotype C（C2）is a predominant HBV genotype among people with chronic HBV infections in Shanxi province.HBV subgenotypes Ba and C2 have no significant difference in virologic,biochemi-cal,and immunologic response to ADV or ETV.