肝组织HBV DNA在抗病毒治疗中的变化与作用

Role of intrahepatic HBV DNA in antivirus therapy

目的探讨肝组织HBV DNA在抗病毒治疗中的变化及其作用。方法71例HBeAg阳性的慢性乙肝患者分别接受序贯治疗、拉米夫定和干扰素抗病毒治疗,总疗程为48周,随访24周。检测治疗前、后肝组织HBV DNA。用限制性片段长度多态性方法进行HBV基因分型。结果应答者肝组织HBV DNA基线值明显低于其它组患者(P=0.0013),治疗48周后其对数均值从5.9±1.0降至4.5±1.2,明显低于无应答或反跳患者(P=0.0073)。治疗48周肝组织HBV DNA对数浓度<5的患者,肝组织HBV DNA对数均值从5.8±1.0降至3.8±0.9,明显低于治疗48周肝组织HBV DNA对数浓度>5的患者(P=0);但停药24周后,两组患者血HBV DNA及ALT均值均无统计学差异(P>0.05)。停药24周后出现反跳的患者,其治疗前、后各项指标与持续应答者无统计学差异(P>0.05)。C基因型(61例)和B基因型(10例)慢乙肝患者肝组织HBV DNA含量治疗前、后无统计学差异。结论抗病毒治疗可明显抑制肝组织HBV DNA的含量,肝组织HBV DNA低水平患者易获得较好的疗效。肝细胞内HBV DNA的消失可能是判断抗病毒治疗终点的理想指标。C、B基因型慢乙肝患者肝组织HBV DNA含量无明显差异,抗病毒治疗疗效相近。

AIM： To study the role of intrahepatic HBV DNA in antiviral therapy. METHODS： 71 patients with HBeAg-positive chronic hepatitis B were studied. Twelve patients were treated with INF-α2b; thirty-five patients received lamivudine; twenty-four patients were administered by sequential therapy with Lamivudine-INF-α2b（at first, lamivudine alone from first to 6th month, then lamivudine combined with INF-α2b from 7th to 8th month,fmally INF-α2b alone from 9th to 12th month）. Liver biopsy specimens were obtained before and after treatment. Blood samples were collected once a month during the period of treatment, in the third month, and in the sixth month after cessation of therapy. Serum and intrahepatie HBV DNA were measured quantitatively by real-time polyInerase chain reaction. HBV genotypes were analyzed by PCR-RFLP.RESULTS： There was no significant difference in intrahepatie HBV DNA levels between the patients infected by HBV genotype C （60 eases） and genotype B （ 10 eases） （ P 〉 0.05）. Intrahepatic HBV DNA logarithm levels in the patients with therapy response decreased from （5.9± 1.0） to （4.5±1.2） （P 〈 0.05）. Patients with intrahepatie HBV DNA logarithm level 〈 5 after treatment achieved higher serum HBV DNA undetectable rate and serum ALT normalization. However, after withdrawal of antiviral drugs. the mean levels of serum HBV DNA and ALT flared up. CONCLUSION： The intrahepatic HBV DNA load can be significantly inhibited by antiviral agents. The patients with lower levels of intrahepatie HBV DNA have better therapy response. Intrahepatie HBV DNA loss may be a significant marker for the endpoint of antiviral treatment. There is no significant difference in intrahepatie HBV DNA levels between the patients infected with HBV genotype C and genotype B.