慢性乙型肝炎病毒基因型与拉米夫定疗效关系的研究

Study on the Relation between HBV Genotype and Therapy of Lamivadine

目的:研究乙型肝炎病毒(HBV)基因型对拉米夫定抗病毒疗效的影响。方法:回顾性调查286例拉米夫定治疗组和对照组患者的临床资料。结果:HBV优势基因型是B(34％)和C(48％)型,共235例。135例患者接受拉米夫定抗病毒治疗,对照组100例。拉米夫定有效率在B、C两基因型中分别为92.9％和75.9％(P=0.02),而对照组分别为9.8％和8.5％(P=0.59);YMDD变异发生率为8.9％和22.8％(P=0.028)。Multivariate分析发现,B基因型、ALT升高、HBV DNA低水平是影响抗病毒应答的预测因素。在ALT升高患者中,B、C基因型拉米夫定有效率分别为93％和77％(P=0.01),对照组为13％和8％(P=0.45)。Multivariate分析发现,B基因型、HBV DNA低水平是预测较好疗效的独立因素。结论:B基因型HBV对拉米夫定的应答率高于C型,而变异YMDD发生率低于C型,基因型是影响拉米夫定疗效和诱导变异的重要因素之一。

Objective: To determine the effects of HBV genotypes on Larnivudine response in patients with HBV DNA positive chronic hepatitis.Methods: Clinical data from 286 patients in the original trial were analyzed.Results: The majority of patients had HBV genotypes B (97 cases, 34%) and C (138 cases, 48%) 135 patients received Lamivadine and 100 received no treatment (controls) . Antiviral response was achieved in 92.9 % and 75.9 % of Lamivadine - treated patients (P = 0.02) and in 9.8% and 8.5% of untreated controls (F = 0.59) with HBV genotype B and C, respectively.The incidences of Lamivudine - induced mutation in YMDD motif were 8.9% and 22.8% (P = 0.028) . Multivariate analysis identified HBV genotype B, elevated pretreatment alanine aminotransferase (ALT) levels, and low pretreatment HBV-DNA levels but not Lamivadine treatment as independent factors associated with antiviral response. Among the patients with elevated pretreatment ALT level, antiviral response was achieved in 93% and 77% of Lamivadine treated patients (P = 0.01), and in 13% and 8% of untreated controls (P = 0.45) with HBV genotype B and C, respectively. Multivariate analysis showed that genotype B and low pretreatment HBV DNA levels were independent predictors of antiviral response.Conclusion: HBV genotype B was associated with a higher rate of Lamivadine- induced HBV DNA clearance and lower rate of Lamivadine - induced YMDD mutation compared with genotype C.HBV genotypes may be an important determinant of antiviral therapy of chronic hepatitis B.