We evaluated the clinical course of patients with chronic hepatitis B who showed viral breakthrough during long-term lamivudine therapy.
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.
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).
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.
Lai, CL, Chien, RN, Leung, NWY, Chang, TT, Guan, R, Tai, DI, et al. 1998A 1-year trial of lamivudine for chronic hepatitis BN Engl J Med339618PubMedGoogle Scholar
Dienstag, JL, Schiff, ER, Wright, TL, Perrillo, RP, Hann, HW, Goodman, Z, et al. 1999Lamivudine as initial treatment for chronic hepatitis B in the United StatesN Engl J Med341125663PubMedGoogle Scholar
Kweon, YO, Goodman, ZD, Dienstag, JL, Schiff, ER, Brown, NA, Burchardt, E, et al. 2001Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis BJ Hepatol3574955PubMedGoogle Scholar
Farrell, GC 2000Clinical potential of emerging new agents in hepatitis BDrugs6070110PubMedGoogle Scholar
Liaw, YF, Chien, RN, Yeh, CT, Tsai, SL, Chu, CM 1999Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapyHepatology3056772PubMedGoogle Scholar
Nafa, S, Ahmed, S, Tavan, D, Pichoud, C, Berby, F, Studyver, L, et al. 2000Early detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis BHepatology32107888PubMedGoogle Scholar
Yuen, MF, Kato, T, Mizokami, M, Chan, AO, Yuen, JC, Yuan, HJ, et al. 2003Clinical outcome and virologic profiles of severe hepatitis B exacerbation due to YMDD mutationsJ Hepatol398505PubMedGoogle Scholar
Kumashiro, R, Kuwahara, R, Ide, T, Koga, Y, Arinaga, T, Hisamochi, A, et al. 2003Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudineIntervirology463504PubMedGoogle Scholar
Mayerat, C, Mantegani, A, Frei, PC 1999Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?J Viral Hepat6299304PubMedGoogle Scholar
Orito, E, Mizokami, M, Sakugawa, H, Michitaka, K, Ishikawa, K, Ichida, T, et al. 2001A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV Genotype Research GroupHepatology3321823PubMedGoogle Scholar
Suzuki, F, Tsubota, A, Akuta, N, Someya, T, Kobayashi, M, Suzuki, Y, et al. 2002Interferon for treatment of breakthrough infection with hepatitis B virus mutants developing during long-term lamivudine therapyJ Gastroenterol379227PubMedGoogle Scholar
Kobayashi, S, Shimada, K, Suzuki, H, Tanikawa, K, Sata, M 2000Development of a new method for detecting a mutation in the gene encoding hepatitis B virus reverse transcriptase active site (YMDD motifHepatol Res173142Google Scholar
Yuen, MF, Sablon, E, Hui, CK, Yuan, HJ, Decraemer, H, Lai, CL 2001Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapyHepatology3478591PubMedGoogle Scholar
Ide, T, Kumashiro, R, Hino, T, Murashima, S, Ogata, K, Koga, Y, et al. 2001Transcription-mediated amplification is more useful in the follow-up of patients with chronic hepatitis B treated with lamivudineHepatol Res217684PubMedGoogle Scholar
Akuta, N, Suzuki, F, Kobayashi, M, Matsuda, M, Sato, J, Takagi, K, et al. 2003Virological and biochemical relapse according to YMDD motif mutant type during long-term lamivudine monotherapyJ Med Virol7150410PubMedGoogle Scholar
Leung, NW, Lai, CL, Chang, TT, Guan, R, Lee, CM, Ng, KY, et al. 2001Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapyHepatology33152732PubMedGoogle Scholar
Liaw, YF, Leung, NW, Chang, TT, Guan, R, Tai, DI, Nq, KY, et al. 2000Effects of extended lamivudine therapy in Asian patients with chronic hepatitis BGastroenterology11917280PubMedGoogle Scholar
Dienstag, JL, Goldin, RD, Heathcote, EJ, Hann, HW, Woessner, M, Stephenson, SL, et al. 2003Histological outcome during long-term lamivudine therapyGastroenterology12410517PubMedGoogle Scholar
Lok, SF, Lai, CL, Leung, N, Yao, GB, Cui, ZY, Schiff, ER, et al. 2003Long-term safety of lamivudine treatment in patients with chronic hepatitis BGastroenterology125171422PubMedGoogle Scholar
Desmet, VJ, Gerber, M, Hoofnagle, JH, Manns, M, Scheuer, PJ 1994Classification of chronic hepatitis: diagnosis, grading and stagingHepatology19151320Google Scholar