Shindo Michiko, Hamada Kazushige, Nishioji Kenichi, Muramatsu Akira, Oda Yoko, Okuno Tadao
Division of Liver Diseases, Department of Internal Medicine, Akashi Municipal Hospital, Japan.
J Gastroenterol. 2004;39(3):260-7. doi: 10.1007/s00535-003-1293-6.
To determine the best indicator of the effective use of interferon and lamivudine for the treatment of hepatitis B e antigen-positive chronic hepatitis, we retrospectively analyzed histologic and virologic status in 200 patients who were treated with interferon and 45 patients who were treated with lamivudine.
Histological grading and staging scores were determined by international criteria and the METAVIR scoring system. The YMDD motif associated with lamivudine resistance was analyzed by the sequencing of hepatitis B virus (HBV) DNA.
Of 200 interferon-treated patients, 62 (31%) seroconverted to anti-hepatitis B e (anti-HBe). Multivariate analysis showed that the significantly important predictors of response were a higher grading score (P = 0.0056) and lower staging score (P = 0.0010). Twenty (44%) of the 45 lamivudine-treated patients seroconverted to anti-HBe, and multivariate analysis showed that the significantly important predictors of response were a higher alanine aminotransferase (ALT) level (P = 0.0034) and lower hepatitis B e antigen levels ( P = 0.0128). YMDD mutations occurred during therapy in 12 patients (27%). The significantly important predictor of the development of mutation was a higher staging score (P = 0.0226).
Both interferon and lamivudine were effective for patients with high ALT levels, but interferon's efficacy appeared to be limited by the degree of fibrosis. Lamivudine appeared to be effective irrespective of the degree of fibrosis, but YMDD mutations seemed to develop sooner in patients with advanced liver fibrosis.
为确定干扰素和拉米夫定治疗乙肝e抗原阳性慢性肝炎的最佳疗效指标，我们回顾性分析了200例接受干扰素治疗的患者和45例接受拉米夫定治疗的患者的组织学和病毒学状况。
采用国际标准和METAVIR评分系统确定组织学分级和分期分数。通过乙肝病毒（HBV）DNA测序分析与拉米夫定耐药相关的YMDD基序。
在200例接受干扰素治疗的患者中，62例（31%）血清转化为抗乙肝e抗体（抗-HBe）。多因素分析显示，反应的显著重要预测因素是较高的分级分数（P = 0.0056）和较低的分期分数（P = 0.0010）。45例接受拉米夫定治疗的患者中有20例（44%）血清转化为抗-HBe，多因素分析显示，反应的显著重要预测因素是较高的丙氨酸转氨酶（ALT）水平（P = 0.0034）和较低的乙肝e抗原水平（P = 0.0128）。12例患者（27%）在治疗期间发生YMDD突变。突变发生的显著重要预测因素是较高的分期分数（P = 0.0226）。
干扰素和拉米夫定对ALT水平高的患者均有效，但干扰素的疗效似乎受纤维化程度限制。拉米夫定似乎无论纤维化程度如何均有效，但在晚期肝纤维化患者中YMDD突变似乎出现得更早。
