Partial Virological Response to Adefovir Add-On Lamivudine Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

被引:2
作者
Chon, Young Eun [1 ]
Park, Jun Yong [1 ,2 ]
Ahn, Sang Hoon [1 ,2 ,3 ]
Kim, Do Young [1 ,2 ]
Han, Kwang-Hyub [1 ,2 ,3 ]
Chon, Chae Yoon [1 ,2 ]
Choi, Ara [1 ]
Kim, Seung Up [1 ,2 ]
机构
[1] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea
[2] Liver Cirrhosis Clin Res Ctr, Seoul, South Korea
[3] Brain Korea 21 Project Med Sci, Seoul, South Korea
关键词
Add-on therapy; Adefovir; Chronic hepatitis B; Hepatitis B virus DNA; Hepatitis B virus; Lamivudine; Nucleos(t)ide analogue; Partial virological response; Virological response; DIPIVOXIL MONOTHERAPY; COMBINATION THERAPY; VIRUS-INFECTION; NUCLEOSIDE/NUCLEOTIDE ANALOGS; NATURAL-HISTORY; YMDD VARIANTS; ENTECAVIR; MANAGEMENT; MUTATIONS; GENOTYPE;
D O I
10.1159/000348853
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: In patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB) receiving adefovir (ADV) add-on LAM therapy, insufficient viral suppression or the appearance of additional ADV resistance has remained unresolved. This study determined the partial virological response (PVR) criteria to predict a virological response (VR) at week 96 in these patients. Methods: 96 patients with LAM-resistant CHB (ADV add-on LAM therapy >2 years) were analyzed. For predicting VR at week 96, the area under the receiver operating characteristic curve values at different time points were compared to establish the optimal time point, and the maximal Youden index was calculated to determine the optimal cut-off hepatitis B virus (HBV) DNA level. Results: 50 (52.1%) patients achieved VR at 2 years after ADV add-on LAM therapy. The optimal PVR criteria were determined to be HBV DNA 500 IU/ml at week 48. 44 (45.8%) patients who met optimal PVR criteria showed a significantly higher risk for detectable HBV DNA levels at week 96 than those with a favorable VR (HBV DNA <500 IU/ml) at week 48. Conclusions: This study suggested optimal PVR criteria in patients with LAM-resistant CHB receiving ADV add-on LAM therapy. Modification of the antiviral agent regimen should be considered if the serum HBV DNA level exceeds 500 IU/ml at week 48. Copyright (C) 2013 S. Karger AG, Basel
引用
收藏
页码:196 / 203
页数:8
相关论文
共 41 条
[1]   Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance [J].
Ahn, SH ;
Park, YN ;
Park, JY ;
Chang, HY ;
Lee, JM ;
Shin, JE ;
Han, KH ;
Park, C ;
Moon, YM ;
Chon, CY .
JOURNAL OF HEPATOLOGY, 2005, 42 (02) :188-194
[2]   Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir [J].
Brunelle, MN ;
Jacquard, AC ;
Pichoud, C ;
Durantel, D ;
Carrouée-Durantel, S ;
Villeneuve, JP ;
Trépo, C ;
Zoulim, F .
HEPATOLOGY, 2005, 41 (06) :1391-1398
[3]   Association of Lamivudine-Resistant Mutational Patterns With the Antiviral Effect of Adefovir in Patients With Chronic Hepatitis B [J].
Cha, Choong Keun ;
Kwon, Hyeok Choon ;
Cheong, Jae Youn ;
Cho, Sung Won ;
Hong, Sun Pyo ;
Kim, Soo-Ok ;
Yoo, Wang Don .
JOURNAL OF MEDICAL VIROLOGY, 2009, 81 (03) :417-424
[4]   Partial virological response to entecavir in treatment-naive patients with chronic hepatitis B [J].
Chon, Young Eun ;
Kim, Seung Up ;
Lee, Chun Kyon ;
Heo, Jeong ;
Kim, Ja Kyung ;
Yoon, Ki Tae ;
Cho, Mong ;
Lee, Kwan Sik ;
Kim, Dong Hwan ;
Choi, Eun Hee ;
Park, Jun Yong ;
Kim, Do Young ;
Chon, Chae Yoon ;
Han, Kwang-Hyub ;
Ahn, Sang Hoon .
ANTIVIRAL THERAPY, 2011, 16 (04) :469-477
[5]  
Fung J, 2007, ANTIVIR THER, V12, P41
[6]   Virologic response and resistance to adefovir in patients with chronic hepatitis B [J].
Fung, SK ;
Chae, HB ;
Fontana, RJ ;
Conjeevaram, H ;
Marrero, J ;
Oberhelman, K ;
Hussain, M ;
Lok, ASF .
JOURNAL OF HEPATOLOGY, 2006, 44 (02) :283-290
[7]   Lamivudine-resistant chronic hepatitis B: An observational study on adefovir in monotherapy or in combination with lamivudine [J].
Gala, Silvia ;
Barbon, Valeria ;
Smedile, Antonina ;
Olivero, Antonella ;
Carenzi, Silvia ;
Lagget, Marco ;
Alessandria, Carlo ;
Rizzetto, Mario ;
Marzano, Alfredo .
JOURNAL OF HEPATOLOGY, 2008, 48 (04) :540-547
[8]   A METHOD OF COMPARING THE AREAS UNDER RECEIVER OPERATING CHARACTERISTIC CURVES DERIVED FROM THE SAME CASES [J].
HANLEY, JA ;
MCNEIL, BJ .
RADIOLOGY, 1983, 148 (03) :839-843
[9]   Detection of hepatitis B virus YMDD variants using mass spectrometric analysis of oligonucleotide fragments [J].
Hong, SP ;
Kim, NK ;
Hwang, SG ;
Chung, HJ ;
Kim, S ;
Han, JH ;
Kim, HT ;
Rim, KS ;
Kang, MS ;
Yoo, W ;
Kim, SO .
JOURNAL OF HEPATOLOGY, 2004, 40 (05) :837-844
[10]   Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern [J].
Inoue, J. ;
Ueno, Y. ;
Wakui, Y. ;
Niitsuma, H. ;
Fukushima, K. ;
Yamagiwa, Y. ;
Shiina, M. ;
Kondo, Y. ;
Kakazu, E. ;
Tamai, K. ;
Obara, N. ;
Iwasaki, T. ;
Shimosegawa, T. .
JOURNAL OF VIRAL HEPATITIS, 2011, 18 (03) :206-215