Poynard Thierry, Zoulim Fabien, Ratziu Vlad, Degos Françoise, Imbert-Bismut Francoise, Deny Paul, Landais Paul, El Hasnaoui Abdelkader, Slama Alain, Blin Patrick, Thibault Vincent, Parvaz Parviz, Munteanu Mona, Trepo Christian
Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
Am J Gastroenterol. 2005 Sep;100(9):1970-80. doi: 10.1111/j.1572-0241.2005.41957.x.
The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression.
Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis.
Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001).
In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.
无创血清标志物FibroTest - ActiTest（FT - AT）可作为慢性丙型和乙型肝炎患者肝活检的替代方法。本研究旨在对接受拉米夫定治疗的患者进行前瞻性研究，以评估治疗效果以及与纤维化进展相关的因素。
法国50家医院的298例患者纳入前瞻性纵向研究。在基线时以及拉米夫定100mg治疗6、12和24个月后测量FT - AT。通过单因素和多因素分析对流行病学、临床和病毒学特征进行分析。
283例患者纳入分析。FT - AT与肝活检结果的准确性通过ROC曲线下面积验证，桥接纤维化的曲线下面积为0.77（标准误 = 0.03），重度活动（A3）的曲线下面积为0.75（标准误 = 0.06）。在多因素分析中，基线时桥接纤维化（METAVIR分期F2 - F3 - F4）与男性性别和年龄高度相关（p < 0.001），与抗-HBe阳性（p = 0.05）和非亚裔种族（p = 0.046）呈边缘相关。拉米夫定治疗总体影响非常显著。FT从基线时的0.51显著降至24个月时的0.37（p < 0.001），85%的患者在24个月时有改善。AT也从0.56显著降至0.13（p < 0.0001），91%的患者在24个月时有改善。观察到纤维化和活动均呈现三相动力学；在最初6个月有显著改善，随后在6至12个月出现平台期，在12至24个月又有改善。YMDD变异的出现并不能完全解释这些三相变化。亚洲患者（p = 0.01）和40岁以下患者（p < 0.001）在第一阶段对纤维化率的影响更高。
在慢性乙型肝炎患者中，24个月的拉米夫定治疗导致通过无创标志物评估的坏死性炎症分级和纤维化分期显著降低，呈现三相动力学。FT - AT在拉米夫定治疗的无创随访中应具有实用价值。
