Clinical course of patients with chronic hepatitis B with viral breakthrough during long-term lamivudine treatment

被引:5
作者
Ide, T [1 ]
Kumashiro, R [1 ]
Kuwahara, R [1 ]
Koga, H [1 ]
Koga, Y [1 ]
Hino, T [1 ]
Tanaka, K [1 ]
Hisamochi, A [1 ]
Ogata, K [1 ]
Sata, M [1 ]
机构
[1] Kurume Univ, Sch Med, Dept Internal Med 2, Kurume, Fukuoka 8300011, Japan
关键词
lamivudine; viral breakthrough; breakthrough hepatitis; YMDD mutants;
D O I
10.1007/s00535-005-1597-9
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background. We evaluated the clinical course of patients with chronic hepatitis B who showed viral breakthrough during long-term lamivudine therapy. Methods. We initially studied 141 patients treated with lamivudine for 1 year or more, and 49 patients who showed viral breakthrough were the subjects of this study. Their mean lamivudine administration period was 2.3 +/- 0.9 years. Results. After viral breakthrough, breakthrough hepatitis occurred in 47 patients (95.9%), but did not occur in the other 2 (4.1%). Four of the 47 patients with breakthrough hepatitis were observed without further treatment, and the alanine transferase (ALT) level was normalized in 2 of them but fluctuated in the other 2. Breakthrough hepatitis was treated by injection of glycyrrhizin or ursodeoxycholic acid administration in 36 of the remaining 43 patients, and by antiviral drug administration in the other 7 (entecavir in 2 patients, adefovir in 2, and interferon in 3). The ALT level was normalized in 5 of the 36 patients treated with glycyrrhizin or ursodeoxycholic acid, but persistently fluctuated in the other 31. In those with normalized ALT after the occurrence of breakthrough hepatitis, the peak ALT level at that point was significantly lower (86 +/- 47 IU/l) than that in the patients without normalization (206 +/- 167 IU/l). Conclusions. These results showed that there were a few patients who did not develop breakthrough hepatitis after showing viral breakthrough, and some who showed normalization of the ALT level after the occurrence of breakthrough hepatitis, but in many patients, ALT continuously fluctuated.
引用
收藏
页码:625 / 630
页数:6
相关论文
共 20 条
[1]   Early detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis B [J].
Ahmed, SNS ;
Tavan, D ;
Pichoud, C ;
Berby, F ;
Stuyver, L ;
Johnson, M ;
Merle, P ;
Abidi, H ;
Trépo, C ;
Zoulim, F .
HEPATOLOGY, 2000, 32 (05) :1078-1088
[2]   Irological and biochemical relapse according to YMDD motif mutant type during long-term lamivudine monotherapy [J].
Akuta, N ;
Suzuki, F ;
Kobayashi, M ;
Matsuda, M ;
Sato, J ;
Takagi, K ;
Tsubota, A ;
Suzuki, Y ;
Hosaka, T ;
Someya, T ;
Kobayashi, M ;
Saitoh, S ;
Arase, Y ;
Ikeda, K ;
Kumada, H .
JOURNAL OF MEDICAL VIROLOGY, 2003, 71 (04) :504-510
[3]  
DESMET VJ, 1994, HEPATOLOGY, V19, P1513, DOI 10.1002/hep.1840190629
[4]   Lamivudine as initial treatment for chronic hepatitis B in the United States [J].
Dienstag, JL ;
Schiff, ER ;
Wright, TL ;
Perrillo, RP ;
Hann, HWL ;
Goodman, Z ;
Crowther, L ;
Condreay, LD ;
Woessner, M ;
Rubin, M ;
Brown, NA .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (17) :1256-1263
[5]   Histological outcome during long-term lamivudine therapy [J].
Dienstag, JL ;
Goldin, RD ;
Heathcote, EJ ;
Hann, HWL ;
Woessner, M ;
Stephenson, SL ;
Gardner, S ;
Gray, DF ;
Schiff, ER .
GASTROENTEROLOGY, 2003, 124 (01) :105-117
[6]   Clinical potential of emerging new agents in hepatitis B [J].
Farrell, GC .
DRUGS, 2000, 60 (04) :701-710
[7]   Transcription-mediated amplification is more useful in the follow-up of patients with chronic hepatitis B treated with lamivudine [J].
Ide, T ;
Kumashiro, R ;
Hino, T ;
Murashima, S ;
Ogata, K ;
Koga, Y ;
Sata, M .
HEPATOLOGY RESEARCH, 2001, 21 (01) :76-84
[8]   Development of a new method for detecting a mutation in the gene encoding hepatitis B virus reverse transcriptase active site (YMDD motif) [J].
Kobayashi, S ;
Shimada, K ;
Suzuki, H ;
Tanikawa, K ;
Sata, M .
HEPATOLOGY RESEARCH, 2000, 17 (01) :31-42
[9]   Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine [J].
Kumashiro, R ;
Kuwahara, R ;
Ide, T ;
Koga, Y ;
Arinaga, T ;
Hisamochi, A ;
Ogata, K ;
Tanaka, K ;
Sata, M .
INTERVIROLOGY, 2003, 46 (06) :350-354
[10]   Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B [J].
Kweon, YO ;
Goodman, ZD ;
Dienstag, JL ;
Schiff, ER ;
Brown, NA ;
Burkhardt, E ;
Schoonhoven, R ;
Brenner, DA ;
Fried, MW .
JOURNAL OF HEPATOLOGY, 2001, 35 (06) :749-755