慢性乙型肝炎患者恩替卡韦治疗后肝纤维化逆转的影响因素分析

王建军; 纪冬; 陈艳; 董政; 杨永平

doi:10.3969/j.issn.2095-5227.2022.07.001

慢性乙型肝炎患者恩替卡韦治疗后肝纤维化逆转的影响因素分析

Factors associated with hepatic fibrosis reversal after entecavir treatment in patients with chronic hepatitis B

摘要

摘要:
背景乙型肝炎病毒(hepatitis B virus，HBV)感染是引起肝纤维化、肝硬化的重要原因，口服核苷(酸)类似物抗病毒治疗获得持续的生化学和病毒学应答可以使肝纤维化好转，但部分慢性乙肝患者的肝纤维化仍可进展。
目的分析慢性乙型肝炎患者应用恩替卡韦抗病毒治疗后肝纤维化逆转的影响因素。
方法本研究为进一步分析一项前瞻性随机双盲安慰剂对照临床研究数据，选取2013年10月- 2014年10月解放军总医院第五医学中心等共14家医院收治的慢性乙肝初治患者，给予恩替卡韦治疗，并在治疗基线和第72周进行配对肝活检。按照治疗72周后是否获得肝纤维化逆转(Ishak纤维化评分下降F≥1分)分为逆转组和无逆转组，采用多因素logistic回归方法筛选肝纤维化逆转因素。
结果 357例患者进行了配对肝活检，被纳入分析，平均年龄(42.4±10.1)岁，男性246例(68.9%)，HBeAg阳性209例(58.5%)。治疗72周后获得肝纤维化逆转者165例(46.2%)，未获得逆转者192例(53.7%)。多因素logistic回归分析显示基线肝弹性检测(liver stiffness measurement，LSM)值(9.4 ~ 17.0 kPa组，OR=0.509，95% CI：0.301 ~ 0.860，P=0.012；＞17.0 kPa组，OR=0.472，95% CI：0.252 ~ 0.882，P=0.019)和血小板(platelet，PLT)＞85 × 10⁹ L⁻¹(OR=2.683，95% CI：1.068 ~ 6.742，P=0.036)与肝纤维化逆转独立关联，年龄和HBV DNA定量与肝纤维化逆转无关。
结论肝纤维化经抗病毒治疗后可以获得组织学逆转；恩替卡韦抗病毒治疗期间，基线较低LSM值和较高PLT的患者更易获得肝纤维化逆转。

Abstract:
Background Hepatitis B virus infection is an important cause of liver fibrosis and cirrhosis. Antiviral therapy with nucleoside/nucleotide analogues and in turn achieving sustained biochemical and virological responses can improve liver fibrosis, but liver fibrosis in some patients is still progressing. It is necessary to know whether there are factors affecting the reversal of liver fibrosis after antiviral treatment.
Objective To analyze the influencing factors for the regression of liver fibrosis in patients with hepatitis B during entecavir (ETV) antiviral treatment.
Methods This study was a further analysis of a prospective randomized double-blind placebo-controlled clinical study. Patients with chronic hepatitis B who were admitted to 14 hospitals from October 2013 to October 2014 were selected for primary treatment with ETV. The paired liver biopsies were performed at treatment baseline and the 72nd week. These individuals were divided into regression and non-regression groups according to whether they achieved regression of liver fibrosis (decrease in Ishak fibrosis score of F ≥ 1 point) after 72 weeks of treatment, and risk factors of hepatic fibrosis regression were screened by multivariable logistic regression.
Results Totally 357 patients who had paired liver biopsies were included in this analysis. The mean age was 42.4 ± 10.1 years, 246 patients (68.9%) were male, and 209 patients (58.5%) were positive for HBeAg. Of the 357 cases, 165 (46.2%) patients achieved regression of liver fibrosis and 192 cases (53.7%) did not achieve regression. Multivariable logistic regression analysis showed that the baseline LSM values (9.4-17.0 kPa OR=0.509, 95% CI: 0.301-0.860, P=0.012; ≥17.0 kPa, OR=0.472, 95% CI: 0.252-0.882, P=0.019) and PLT＞85 × 10⁹ L⁻¹ (OR=2.683, 95% CI: 1.068-6.742, P=0.036) were the independent factors associated with the regression of liver fibrosis. Nevertheless, age and HBV DNA level at treatment baseline had no impact on the regression of liver fibrosis.
Conclusion Liver fibrosis can be reversed by anti-HBV treatment, patients with lower LSM and higher PLT values at baseline are easy to achieve regression of fibrosis during ETV antiviral treatment.

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