替比夫定治疗乙型肝炎肝硬化失代偿疗效分析及对肾脏功能的影响

肝脏 ›› 2016, Vol. 21 ›› Issue (9): 722-725.

替比夫定治疗乙型肝炎肝硬化失代偿疗效分析及对肾脏功能的影响

高得勇, 王迎迎, 汪妍妍, 徐国荣, 吴剑琴, 夏利萍, 刘亮明

201600 上海交通大学附属第一人民医院松江分院感染科

收稿日期:2016-03-11 出版日期:2016-09-30 发布日期:2020-06-19
通讯作者: 高得勇,Email:gaodeyong1970@163.com
基金资助:
上海市松江区计划和生育委员会重点项目(2012-III-06)

Efficacy of telbivudine in chronic hepatitis B patients with decompensated liver crirrhosis and its influence on renal function

GAO De-yong, WANG Ying-ying, WANG Yan-yan, XU Guo-rong, WU Jian-qing, XIA Li-ping, LIU Liang-ming

Departmynt of Infectious Diseases, Songjiang Hospital Affiliated to Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai 201600, China

Received:2016-03-11 Online:2016-09-30 Published:2020-06-19
Contact: GAO De-yong, Email: gaodeyong1970@163.com

摘要/Abstract

摘要： 目的评价替比夫定治疗乙型肝炎肝硬化失代偿患者的疗效及对肾脏功能的影响。方法回顾性分析2012年4月至2015年11月在上海市松江区中心医院感染科就诊的失代偿期乙型肝炎肝硬化患者72例, 给予替比夫定抗病毒治疗,在治疗后24周、48周观察血清丙氨酸氨基转移酶(ALT)、血清总胆红素(TBil) 、白蛋白(Alb)、凝血酶原时间(PT) 、Child-Pugh积分、腹水、HBV DNA、阴转率及耐药变异率;比较治疗后24周、48周血清肌酐(CR),估算肾小球滤过率(eGFR)较基线的变化情况。计量资料比较采用独立样本t检验,治疗前后比较采用配对t检验,计数资料采用χ²检验。结果治疗24周时,血清ALT、TBil、HBV DNA载量均值分别为:46.12 U/L、44.31 μmol/L和1.89 lg拷贝/mL,HBV DNA阴转率为75.00%,均较治疗前有明显改善(P<0.05)。2例患者出现耐药变异,但未发现有腹水消失的病例;随着治疗时间延长至48周,Alb水平和PT均值分别为:34.16 g/L和15.09 s,Child-Pugh积分也较治疗前进一步明显改善(P<0.05),有3例患者腹水消失且耐药变异病例增加至5例。治疗48周时eGFR及CR分别为:108.48 mL/(min·1.73 m²)和0.83 mg/dL,均较治疗前明显改善(P<0.05),39例基线肾功能轻度受损[eGFR 60~90 mL/ (min·1.73 m²)]患者中,有9例患者(23.08%)上升至eGFR≥90 mL/(min·1.73 m²)。结论替比夫定治疗乙型肝炎肝硬化失代偿期患者在有效抑制病毒及改善肝脏储备功能方面疗效肯定,随着治疗时间的延长治疗效果更加明显,但有部分患者出现耐药变异;替比夫定有改善肾脏功能的作用,对于基线肾功能受损的患者,其肾脏功能可得到一定程度的恢复。

关键词: 替比夫定, 乙型肝炎, 肝硬化, 疗效, 肾脏功能

Abstract: Objective To investigate the efficacy of telbivudine (LDT) in patients with hepatitis B virus (HBV)-related decompensated liver cirrhosis and evaluate its influence on renal function. Methods In the retrospective analysis, 72 patients with HBV-related decompensated liver cirrhosis in our hospital from April 2012 to October 2015 received LDT (600 mg/d) antiviral therapy. The levels of alanine aminotransferase (ALT), total bilirubin (TBil), albumin (Alb), prothrombin time (PT), ascites, Child-Pugh integral, HBV DNA load, HBV DNA undetectable rate and resistance mutation were evaluated at baseline, week 24 and 48. Serum creatinine (CR) and estimated of glomerular filtration rate (eGFR) were also monitored. Comparisons among baseline, week 24 and 48 were carried out by chi-square test and t-test. Results At week 24, mean levels of ALT, TBil, HBV DNA load and HBV DNA undetectable rate were 46.12 U/L, 44.31 mol/L, 1.89 lg copies/mL and 75.00%, respectively. All results were significantly improved, as compared with those at baseline (P<0.05). Meanwhile, resistance mutations occurred in 2 cases, and ascites regression had not been reported. At week 48, levels of Alb and PT were 34.16 g/L and 15.09 sec, and Child-Pugh integral was significantly decreased as compared to that at baseline (P<0.05). In addition, resistance mutations occurred in 5 cases, and ascites regression was found in 3 cases. Compared with those at baseline, CR level reduced to 0.83 mg/dL and eGFR level raised to 108.48 mL/(min·1.73 m²) after 48-week treatment (P<0.05). Furthermore, 9 (23.08%) patients with mild renal impairment improved with eGFR≥90 mL/(min·1.73 m²). Conclusion LDT is a crucial strategy for inhibiting virus replication and improving liver function in chronic hepatitis B patients with decompensated liver cirrhosis. Although prolonging treatment can enhance therapeutic efficacy, it also increases resistance mutations risk. In terms of patients with mild renal impairment, LDT might be an appropriate option for its improvement in renal function.

Key words: Telbivudine, Chronic hepatitis B, Liver cirrhosis, Efficacy, Renal function

高得勇, 王迎迎, 汪妍妍, 徐国荣, 吴剑琴, 夏利萍, 刘亮明. 替比夫定治疗乙型肝炎肝硬化失代偿疗效分析及对肾脏功能的影响[J]. 肝脏, 2016, 21(9): 722-725.

GAO De-yong, WANG Ying-ying, WANG Yan-yan, XU Guo-rong, WU Jian-qing, XIA Li-ping, LIU Liang-ming. Efficacy of telbivudine in chronic hepatitis B patients with decompensated liver crirrhosis and its influence on renal function[J]. Chinese Hepatolgy, 2016, 21(9): 722-725.

参考文献

[1] 中华医学会肝病学分会中华医学会感染病学分会. 慢性乙型肝炎防治指南 (2010 年版). 肝脏,2011,16:2-16.
[2] Hou J,Yin YK,Xu D,et al. Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B:Results at 1 year of a randomized, double-blind trial. Hepatology,2008,47:447-454.
[3] Lai CL,Gane E,Liaw YF,et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med,2007,357:2576-2588.
[4] Gane EJ,Deray G,Liaw YF,et al. Telbivudine improves renal function in patients with chronic hepatitis B. Gastroenterology,2014,146:138-146.
[5] Levey AS,Stevens LA,Schmid CH,et al. A new equation to estimate glomerular filtration rate. Ann Intern Med,2009,150:604-612.
[6] Cholongitas E,Papatheodoridis GV,Goulis J,et al. The impact of newer nucleos(t)ide analogues on patients with hepatitis B decompensated cirrhosis. Ann Gastroenterol,2015,28:109-117.
[7] Amarapurkar DN. Telbivudine:A new treatment for chronic hepatitis B. World J Gastroenterol,2007,13:6150-6155.
[8] Zhao S,Tang L,Fan X,et al. Comparison of the efficacy of lamivudine and telbivudine in the treatment of chronic hepatitis B: a systematic review. Virol J,2010,7: 211.
[9] Appel G. Viral infections and the kidney: HIV,hepatitis B,and hepatitis C. Cleve Clin J Med, 2007,74:353-360.
[10] Kim YJ, Cho HC, Sinn DH, et al. Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients. J Gastroenterol Hepatol, 2012,27:306-312.
[11] 左璐,孙凤霞,王宪波,等. 298 例乙型肝炎肝硬化患者合并肾功能不全情况分析. 中华肝脏病杂志,2014,22:504-508.
[12] Levey AS,Coresh J,Balk E,et al. National kidney foundation practice guidelines for chronic kidney disease:evaluation, classification, and stratification. Ann Intern Med,2003,139:137-147.
[13] Liaw YF,Gane E,Leung N,et al. 2-year GLOBE trial results:telbivudine Is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology,2009,136:486-495.
[14] Chan HL,Chen YC,Gane EJ,et al. Randomized clinical trial:efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis. J Viral Hepat,2012,19:732-743.
[15] 李小溪,钟春秀,杨淑玲,等. 阿德福韦酯和替比夫定单药治疗慢性乙型肝炎对肾脏功能影响的比较. 南方医科大学学报,2012, 32:826-829.
[16] Hung CH,Hu TH,Lu SN,et al. Tenofovir versus entecavir in treatment of chronic hepatitis B virus with severe acute exacerbation. Antimicrob Agents Chemother,2015,59:3168-3173.
[17] Russ KB,Stevens TM,Singal AK. Acute kidney injury in patients with cirrhosis. J Clin Transl Hepatol,2015,28:195-204.