CAJ | 학술논문

目的评估拉米夫定(LAM)对慢性乙型肝炎伴重度肝纤维化患者长期治疗的临床和组织学结果.方法 39例重度肝纤维化(Ishak评分≥4分)的慢性乙型肝炎患者接受LAM治疗,最长达10年,评估随访期末患者疾病进展、肝组织学、病毒学以及生化学应答.数据分析采用配对t检验、Fisher确切概率法以及Willcoxon检验.结果 28例完成10年随访的患者中,5例出现疾病进展,占1 7.9%.16例患者在随访期末接受了第2次肝组织活检,与基线水平相比,肝组织学活动指数和纤维化评分均有明显好转(1.1±1.4比7.1±3.2,t=-0.82,P＜0.01;3.6±2.2比5.3±0.7,t=-2.89,P＜0.05).其中3例患者纤维比评分由基线时的5分改善为随访期末的0分.27例患者中,3例HBsAg消失,占11%,2例HBsAg血清学转换,占7%.23例HBeAg阳性患者至随访末,19例HBeAg消失,占83%,9例HBeAg血清学转换,占39%.在治疗期间,共有11例患者发生了病毒学突破或检测到LAM相关耐药变异,加用或换用其他核苷酸类似物,随访期末所有患者HBV DNA均＜1×103拷贝/mL.结论 LAM长期治疗能延缓慢性乙型肝炎伴重度肝纤维化患者的疾病进展,提高HBsAg及HBeAg的阴转率,持续维持HBV DNA于低水平,对某些患者能完全逆转肝纤维化,挽救治疗可减少LAM耐药变异对患者预后的影响.
목적 평고랍미부정(LAM)대만성을형간염반중도간섬유화환자장기치료적림상화조직학결과.방법 39례중도간섬유화(Ishak평분≥4분)적만성을형간염환자접수LAM치료,최장체10년,평고수방기말환자질병진전、간조직학、병독학이급생화학응답.수거분석채용배대t검험、Fisher학절개솔법이급Willcoxon검험.결과 28례완성10년수방적환자중,5례출현질병진전,점1 7.9%.16례환자재수방기말접수료제2차간조직활검,여기선수평상비,간조직학활동지수화섬유화평분균유명현호전(1.1±1.4비7.1±3.2,t=-0.82,P＜0.01;3.6±2.2비5.3±0.7,t=-2.89,P＜0.05).기중3례환자섬유비평분유기선시적5분개선위수방기말적0분.27례환자중,3례HBsAg소실,점11%,2례HBsAg혈청학전환,점7%.23례HBeAg양성환자지수방말,19례HBeAg소실,점83%,9례HBeAg혈청학전환,점39%.재치료기간,공유11례환자발생료병독학돌파혹검측도LAM상관내약변이,가용혹환용기타핵감산유사물,수방기말소유환자HBV DNA균＜1×103고패/mL.결론 LAM장기치료능연완만성을형간염반중도간섬유화환자적질병진전,제고HBsAg급HBeAg적음전솔,지속유지HBV DNA우저수평,대모사환자능완전역전간섬유화,만구치료가감소LAM내약변이대환자예후적영향.
Objective To evaluate the clinical and histological outcomes in a cohort of chronic hepatitis B (CHB) patients who had histologically confirmed severe liver fibrosis and received lamivudine (LAM) therapy for up to 10 years. Methods Thirty-nine CHB patients with severe liver fibrosis (Ishak fibrosis score≥4) were treated with LAM for up to 10 years. Disease progression liver histological improvement, virological and biochemical responses were evaluated during follow-up. Data were analyzed using paired t test, Fisher exact test and Willcoxon test. Results Twenty-eight patients completed the 10-year follow-up. There were 5 (17.9% ) patients with disease progression.At the end of follow up, 16 patients received a second liver biopsy, which showed significant improvement of histological activity index (1.1 ± 1.4 vs 7. 1 ± 3.2, t =- 0.82, P＜0.01 ) and Ishak fibrosis score (3.6±2.2 vs 5.3±0.7, t= -2.89, P＜0.05) compared to baseline. There were 3 cases with Ishak fibrosis score improved from F5 to F0. Among 27 patients, 3(11% ) cases achieved hepatitis B surface antigen (HBsAg) loss and 2 (7 % ) achieved HBsAg seroconversion. At the end of follow-up, 19 out of 23 (83% ) hepatitis B e antigen (HBeAg) positive patients obtained HBeAg loss and 9 (39 % ) obtained HBeAg seroconversion. During LAM treatment, 11 patients experienced virological breakthrough or detected documented LAM-related resistance mutation. The viral loads of all patients were below 1 ×103 copy/mL at the end of follow-up after rescued by add-on or switch to another nucleotide analog.Conclusions Long-term LAM therapy can delay the disease progression in CHB patients with severe liver fibrosis, increase HBsAg and HBeAg loss rates, sustain suppression of HBV replication at a low level and even totally reverse the liver fibrosis in some patients. The effect of LAM resistance mutation on disease outcomes would be reduced by rescue therapy.