长期使用替比夫定治疗可使慢性乙型肝炎患者的肝脏炎症和纤维化消退。
Long-Term Telbivudine Treatment Results in Resolution of Liver Inflammation and Fibrosis in Patients with Chronic Hepatitis B.
作者信息
Hou Jin-Lin, Xu Daozheng, Shi Guangfeng, Wan Mobin, Goodman Zachary, Tan Deming, Xie Qing, Chen Chengwei, Wei Lai, Niu Junqi, Wang Qinhuan, Ren Hong, Wang Yuming, Jia Jidong, Bao Weibin, Dong Yuhong, Trylesinski Aldo, Naoumov Nikolai V
机构信息
Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Beijing Ditan Hospital, Beijing, China.
出版信息
Adv Ther. 2015 Aug;32(8):727-41. doi: 10.1007/s12325-015-0232-2. Epub 2015 Sep 2.
INTRODUCTION
The long-term goal of chronic hepatitis B (CHB) treatment is improvement of liver disease and prevention of cirrhosis. The aim of this study was to assess whether prolonged telbivudine treatment improves liver inflammation and fibrosis. The primary objective was to evaluate the proportion of patients with absence/minimal inflammation (Knodell necroinflammatory score ≤3) on liver biopsy at Year 5.
METHODS
Fifty-seven patients aged 16-70 years with a clinical history of CHB and active viral replication (38 hepatitis B e antigen [HBeAg] positive and 19 HBeAg negative) were followed for 6 years: 33 received telbivudine 600 mg/day continuously for 5 years; 24 received lamivudine 100 mg/day for 2 years and then telbivudine for 3 years. Liver biopsies were taken pre-treatment and after 5 years of treatment.
RESULTS
At baseline, mean (standard deviation) serum hepatitis B virus (HBV) DNA load was 8.5 (1.7) log10 copies/mL, Knodell necroinflammatory score was 7.6 (2.9), and Ishak fibrosis score was 2.2 (1.1). After antiviral treatment (median duration: 261 weeks), liver histology improved with increased proportions of patients with absence/minimal liver inflammation (Knodell necroinflammatory score ≤3), from 16% (9/57) at baseline to 98% (56/57), and absence/minimal fibrosis (Ishak score ≤1), from 25% (14/57) at baseline to 84% (48/57). At Year 5, HBV DNA load was <300 copies/mL for all patients; cumulative HBeAg loss and seroconversion rates were 88% and 77%, respectively. At Year 6, 95% of patients with abnormal baseline glomerular filtration rate (60-90 mL/min/1.73 m(2)) improved to normal GFR (>90 mL/min/1.73 m(2)).
CONCLUSION
Long-term telbivudine treatment with profound and durable viral suppression significantly improved liver histology, thus achieving the long-term goals of CHB treatment. FibroScan(®) results after 5 and 6 years of treatment (in almost 20% of patients) were consistent with this information.
FUNDING
Novartis and National Science and Technology Major Project (2012ZX10002003).
TRIAL REGISTRATION
ClinicalTrials.gov # NCT00877149.
引言
慢性乙型肝炎（CHB）治疗的长期目标是改善肝脏疾病并预防肝硬化。本研究的目的是评估长期使用替比夫定治疗是否能改善肝脏炎症和纤维化。主要目标是评估在第5年时肝活检显示无炎症/轻度炎症（Knodell坏死性炎症评分≤3）的患者比例。
方法
57例年龄在16 - 70岁、有CHB临床病史且病毒活跃复制的患者（38例乙肝e抗原[HBeAg]阳性，19例HBeAg阴性）接受了6年的随访：33例患者连续5年每天服用600 mg替比夫定；24例患者先服用2年每天100 mg拉米夫定，然后服用3年替比夫定。在治疗前和治疗5年后进行肝活检。
结果
基线时，平均（标准差）血清乙肝病毒（HBV）DNA载量为8.5（1.7）log10拷贝/mL，Knodell坏死性炎症评分为7.6（2.9），Ishak纤维化评分为2.2（1.1）。抗病毒治疗后（中位疗程：261周），肝脏组织学得到改善，无炎症/轻度肝脏炎症（Knodell坏死性炎症评分≤3）的患者比例增加，从基线时的16%（9/57）增至98%（56/57），无纤维化/轻度纤维化（Ishak评分≤1）的患者比例从基线时的25%（14/57）增至84%（48/57）。在第5年时，所有患者的HBV DNA载量均<300拷贝/mL；HBeAg累计转阴率和血清学转换率分别为88%和77%。在第6年时，基线肾小球滤过率异常（60 - 90 mL/min/1.73 m²）的患者中有95%的肾小球滤过率恢复正常（>90 mL/min/1.73 m²）。
结论
长期使用替比夫定进行深度且持久的病毒抑制可显著改善肝脏组织学，从而实现CHB治疗的长期目标。治疗5年和6年后（近20%的患者）的FibroScan®结果与该信息一致。
资助
诺华公司和国家科技重大专项（2012ZX10002003）。
试验注册
ClinicalTrials.gov # NCT00877149
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