CASE REPORT 病历报告
HBsAg Seroclearance in Chinese Patients Receiving Lamivudine Therapy for Chronic Hepatitis B Virus Infection
乙型肝炎传染的中国病人接受拉米夫啶治疗的表面抗原血清清除.
Received 2 December 2003/Returned for modification 16 January 2004/Accepted 5 May 2004
病历于2003年12月2日收到/于2004年1月16日返回修改/2004年5月5日接受
We report two Chinese patients in whom lamivudine treatment resulted in HBsAg seroclearance. One patient received lamivudine, and another patient received 12-week famciclovir treatment followed by lamivudine. Lamivudine was maintained after HBeAg seroconversion. These two patients lost HBsAg at 24 and 27 months (ages, 23 and 19.3 years, respectively) and developed measurable titer of anti-HBs after 65 and 71 months of therapy, respectively. The liver biochemistry was normal after HBeAg seroconversion. The serum hepatitis B virus (HBV) DNA levels were undetectable (<200 copies/ml) both at the time of HBeAg seroconversion and at the last follow-up. Liver biopsy of one patient showed nearly normal histology, with undetectable intrahepatic total HBV DNA and covalently closed circular DNA. In conclusion, lamivudine therapy can result in HBsAg seroclearance at an early age even though the phenomenon is rare.
我们报告两位中国患者在接受了拉米夫啶治疗后清除了血清中的表面抗原. 一位病人接受拉米夫啶治疗, 另一位在进行12周FAMCICLOVIR治疗后接受拉米夫啶治疗. 在出现血清转换后继续拉米夫啶治疗. 这两位病人在第24和第27个月时表面抗原转阴, (年龄分别为 23 和 19.3岁), 在治疗的第65和71周时分别出现了可以检测得到的表面抗体. 在E抗原出现血清转化后肝生化指标恢复正常. 两位的HBVDNA在E抗原血清转换后均低于检测标准(小于200拷倍/毫升)并一直持续阴性. 一位病人的肝穿结果显示肝脏组织几乎恢复了正常, 肝内HBVDNA及CCCDNA为检测不到, 结论: 尽管这样的现象较少, 但拉米夫啶治疗可以在很年轻时清除血清中的表面抗原.
下面的内容哪位如果有时间可以帮忙翻译一下. 谢谢.
CASE REPORTS
Case 1.
The first Chinese patient, a 21-year-old male, was randomized to receive 100mg of lamivudine daily from the start of the trial (August 1997). He was found to be HBsAg positive during a routine checkup at age 16. He probably had chronic hepatitis B virus (HBV) infection since childhood, as his sister was also an HBV carrier. He had HBV genotype B (determined by the line probe assay INNO-LiPA HBV Genotyping; Innogenetics NV, Ghent, Belgium). The pretreatment liver biochemistry was as follows: albumin, 45 g/liter; bilirubin, 9 umol/liter; alanine aminotransferase (ALT), 398 U/liter. The HBV DNA level measured by the Cobas Amplicor HBV Monitor test (Roche Diagnostics, Branchburg, N.J.; lower limit of detection of 200 copies/ml) was 7.7 x 10 6 copies/ml. After reaching the peak ALT level of 554 U/liter at week 4 of lamivudine treatment, he had HBeAg seroconversion with undetectable HBV DNA level (<200 copies/ml) at month 3 of therapy (November 1997). He was maintained on lamivudine after HBeAg seroconversion. The HBV DNA level remained undetectable at month y of therapy. He had follow-up every 8 weeks under the trial protocol till week 48. From then on, he had regular follow-up every 3 to 6 months in the Hepatitis Clinic, Queen Mary Hospital, The University of Hong Kong, Hong Kong. The ALT levels were normal throughout the subsequent follow-up. HBsAg became negative at 24 months (at 23 years of age; July 1999). Anti-HBs first became positive, with a titer of 17 Mu/ml, at 65 months (at 26.4 years of age; January 2003). The liver biochemistry at the last follow-up (71.5 months; July 2003) was as follows: albumin 45 g/liter; bilirubin, 8 umol/liter; ALT, 37 U/liter. The serum HBV DNA remained undetectable. Liver biopsy showed minimal necroinflammation (grade 1 out of 18) and fibrosis (grade 1 out of 4) according to the Knodell scoring system (histologic activity index). Both the intrahepatic total HBV DNA and the covalently closed circular (ccc) DNA were undetectable, as measured by the Invader HBV DNA assay (Third Wave Technologies, Inc., Madison, Wis.; lower limits of detection for the relaxed circular and ccc forms of DNA were 10 5 and 10 4 copies/ml of DNA extract, respectively) With all these favorable results, the lamivudine was stopped at 71.5 months (august 2003). Six months after cessation of lamivudine (February 2004), the HBVDNA and HBsAg remained undetectable and the anti-HBs titer was 93 MU/ml.
第一位中国患者, 21岁, 男性, 自1997年8月开始被任选接受每天100毫克拉米夫定治疗的临床试药. 他是在16岁一次理性体检中发现乙肝表面抗原阳性. 很有可能他自幼就感染了乙肝病毒HBV, 他的妹妹也是HBV的带原者. 他所感染的病毒基因是B型 (根据比利时NV Ghent, Innogenetics公司的线性探针检测乙肝病毒基因分析检验方法求证的) 在治疗前的肝脏生化检查是: 白蛋白 45g/liter, 胆红素 9umol/liter, ALT 398 U/liter. HBV DNA水平是用(新泽西州, Branchburg城市的罗氏生物制药公司生产最低监测限度为200拷贝/毫升)的Cobas Amplicor HBV Monitor方法, 为7.7X10 6 拷贝/毫升. 在服用拉米夫定之后4周ALT达到最高峰554U/liter, 在用药后三个月(1997年11月)其HBeAg转阴, HBV DNA监测不到(少于200拷贝/毫升). 他在HBeAg转阴后继续服用拉米夫定. 在治疗后的6个月, HBV DNA持续监测不到. 之后根据试药规定他每8周复检一次, 直到第48周. 之后他每3-6个月去香港大学皇后玛利医院进行一次正常检查.ALT水平在之后的检查中都正常. HBsAg在第24个月的时候开始转阴(在23岁, 1999年7月时). 在第65个月的时候(在26.4岁, 2003年7月时)HBsAb呈现阳性, 其滴度为17Mu/ml. 肝脏生化在最后一次检查时候(71.5 个月; 2003年7月)是: 白蛋白45g/liter, 胆红素8umol/liter, ALT37U/liter. 血清HBV DNA仍然监测不到. 根据Knodell分级系统(HAI)肝穿显示微量坏死性炎症(18级分级为一级), 纤维化(4级中第一级)
Case 2.
The second Chinese patient was a 17-year-old male randomized to receive 500 mg famciclovir three times a day in September 1997 for 12 weeks, followed by 100 mg of lamivudine daily. He was found to be HBsAg positive by screening his blood for donation at age 16. He had HBV genotype C. The pretreatment liver biochemistry was as follows: albumin, 50 g/liter; bilirubin, 8 umol/liter; ALT, 59 U/liter. The HBV DNA level measured by the Cobas Amplicor HBV Monitor test was 6.7 x 10 6 copies/ml. The HBV DNA level decreased to 2.1 x 10 4 copies/ml at month 6 of therapy. He had follow-up every 8 weeks under the trial protocol till week 48. From then onwards, he had regular follow-up every 3 to 6 months in our Hepatitis Clinic, Queen Mary Hospital, The University of Hong Kong. He had fluctuating ALT levels, ranging from 29 to 132 U/liter before achieving HBeAg seroconversion at month 15 of therapy (December 1998). The HBV DNA level was undetectable at the time of HBeAg seroconversion. HBsAg became negative at 27 months (at 19.3 years of age; December 1999). Lamivudine was maintained after HBeAg seroconversion but was stopped after 30 months of therapy on the patient's own initiative (March 2000). Anti-HBs was detectable at the titer of 421.2 MU/liter at the last follow-up (71 months; at 22.9 years of age; August 2003). He had persistent normal ALT levels till the last follow-up. The latest liver biochemistry was as follows: albumin, 43 g/liter; bilinubin, 11 umol/liter; ALT, 12 U/liter. The serum HBV DNA was undetectable. The option of liver biopsy was declined by the patient.
第二名中国患者是一名17岁男性, 自1997年9月被任选临床试药服用泛昔洛韦500毫克每天三次, 为期12周, 之后改用拉米夫定100毫克每天一次. 他是在16岁一次献血筛检中检查到HBeAg阳性. 他感染的HBV病毒基因是C型. 治疗前肝脏生化为: 白蛋白50g/liter, 单红素8umol/liter, ALT59U/liter. HBV DNA水平使用Cobas Amplicor HBV Monitor方法检验是6.7X 10 6 拷贝/毫升. HBV DNA水平在治疗后6个月时减低至2.1X10 4 拷贝/毫升. 之后, 根据试药规定每8周检查一次, 直到第48周为止. 从48周起, 他每3-6个月去香港大学附属皇后玛丽医院肝脏诊所复查一次.在第15个月HBeAg转阴(1998年12月)前, 他的ALT属于上下波动, 持续在29-132U/liter之间. HBV DNA在HBeAg转换的时候监测不到. HBsAg在第27个月的时候(19.3岁, 1999年12月)转阴. 拉米在HBeAg转阴后继续服用, 直到30月时候在患者的要求下停药(2000年3月). HBsAb在最后一次检查(第71个月, 在22.9岁, 2003年8月)时候为421.2MU/liter.其ALT直到上次检查时候维持正常. 最后一次肝脏生化检查为: 白蛋白43 g/liter, 胆红素11umol/liter, ALT12U/liter. HBV DNA为监测不到. 给与患者感穿检查的机会被患者拒绝. [br][br]
[此贴子已经被作者于2005-8-10 16:20:58编辑过] | 
发表于 2005-8-9 03:22
