Kim Min Hwan, Kim Kyung Ah, Lee June Sung, Lee Hyun Woong, Kim Hyung Joon, Yun Sang Gu, Kim Nam Hoon, Bae Won Ki, Moon Young Soo
Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.
Korean J Hepatol. 2009 Sep;15(3):331-7. doi: 10.3350/kjhep.2009.15.3.331.
BACKGROUND/AIMS: Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB.
Data on patients with CHB and detectable serum hepatitis B virus (HBV) DNA who were treated with clevudine for 48 weeks or longer were collected retrospectively for this study. Patients who had taken lamivudine within the 3 years prior to this study were excluded. Serum HBV DNA was measured by polymerase chain reaction hybridization (lower detection limit=316 copies/mL). Serum HBV DNA and biochemical data were analyzed at weeks 24 and 48. Developments of viral breakthrough and resistance to the antiviral drug were also monitored.
Data from 74 patients (mean age 44 years; M:F=54:20; HBeAg-positive, 47; HBeAg-negative, 27) were included in this study. Ten patients had experienced previous lamivudine treatment. Median HBV DNA at baseline was 6.49 log(10) copies/mL. Median serum HBV DNA reductions from baseline at week 48 were -4.34 log(10) copies/mL (HBeAg-positive, -4.84 log(10) copies/mL; HBeAg-negative, -3.74 log(10) copies/mL). At week 48, serum HBV DNA was not detected in 83.8% of the patients (HBeAg-positive, 76.6%; HBeAg-negative, 96.3%). Normalization of serum alanine aminotransferase levels was achieved in 84.7% of the patients. Viral breakthrough and antiviral resistance developed in two patients at week 48. The development of antiviral resistance was associated with the presence of previous lamivudine treatment and cirrhosis.
A 48-week course of clevudine therapy was highly effective in patients with CHB. The risk of development of resistance to clevudine was increased in patients with previous exposure to lamivudine and cirrhosis.
背景/目的：克立夫定是一种核苷类似物，作为慢性乙型肝炎（CHB）的24周治疗方案，具有强效且持久的抗病毒作用。本研究评估了克立夫定治疗CHB 48周疗程的疗效和病毒耐药性。
本研究回顾性收集了接受克立夫定治疗48周或更长时间的CHB患者及可检测到血清乙型肝炎病毒（HBV）DNA患者的数据。排除在本研究前3年内服用过拉米夫定的患者。采用聚合酶链反应杂交法检测血清HBV DNA（最低检测限=316拷贝/毫升）。在第24周和第48周分析血清HBV DNA和生化数据。同时监测病毒突破和抗病毒药物耐药情况。
本研究纳入74例患者（平均年龄44岁；男:女=54:20；HBeAg阳性47例，HBeAg阴性27例）。10例患者曾接受过拉米夫定治疗。基线时HBV DNA中位数为6.49 log(10)拷贝/毫升。第48周时，血清HBV DNA较基线的中位数下降为-4.34 log(10)拷贝/毫升（HBeAg阳性患者为-4.84 log(10)拷贝/毫升；HBeAg阴性患者为-3.74 log(10)拷贝/毫升）。第48周时，83.8%的患者血清HBV DNA未被检测到（HBeAg阳性患者为76.6%，HBeAg阴性患者为96.3%）。84.7%的患者血清丙氨酸氨基转移酶水平恢复正常。第48周时有2例患者出现病毒突破和抗病毒耐药。抗病毒耐药的发生与既往拉米夫定治疗及肝硬化有关。
克立夫定治疗48周疗程对CHB患者非常有效。既往接触过拉米夫定和患有肝硬化的患者对克立夫定产生耐药的风险增加。
