Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy

Yun Jung Chang, Jeong Yoon Yim, Nam Young Cho, Chang Won Choi, Soo Jung Baek, Soo Hyun Ahn, Do Won Choi, Yong Dae Kwon, Sun Suk Kim, Oh Sang Kwon, Ju Hyun Kim, Jong Eun Yeon, Jin Won Song, Kwan Soo Byun, Chang Hong Lee

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Abstract

BACKGROUND/AIMS: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. METHODS: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. RESULTS: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01). CONCLUSIONS: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalTaehan Kan Hakhoe chi = The Korean journal of hepatology
Volume8
Issue number4
Publication statusPublished - 2002 Dec 1

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Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Therapeutics
Restriction Fragment Length Polymorphisms

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Chang, Y. J., Yim, J. Y., Cho, N. Y., Choi, C. W., Baek, S. J., Ahn, S. H., ... Lee, C. H. (2002). Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy. Taehan Kan Hakhoe chi = The Korean journal of hepatology, 8(4), 397-404.

Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy. / Chang, Yun Jung; Yim, Jeong Yoon; Cho, Nam Young; Choi, Chang Won; Baek, Soo Jung; Ahn, Soo Hyun; Choi, Do Won; Kwon, Yong Dae; Kim, Sun Suk; Kwon, Oh Sang; Kim, Ju Hyun; Yeon, Jong Eun; Song, Jin Won; Byun, Kwan Soo; Lee, Chang Hong.

In: Taehan Kan Hakhoe chi = The Korean journal of hepatology, Vol. 8, No. 4, 01.12.2002, p. 397-404.

Research output: Contribution to journalArticle

Chang, YJ, Yim, JY, Cho, NY, Choi, CW, Baek, SJ, Ahn, SH, Choi, DW, Kwon, YD, Kim, SS, Kwon, OS, Kim, JH, Yeon, JE, Song, JW, Byun, KS & Lee, CH 2002, 'Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy', Taehan Kan Hakhoe chi = The Korean journal of hepatology, vol. 8, no. 4, pp. 397-404.
Chang, Yun Jung ; Yim, Jeong Yoon ; Cho, Nam Young ; Choi, Chang Won ; Baek, Soo Jung ; Ahn, Soo Hyun ; Choi, Do Won ; Kwon, Yong Dae ; Kim, Sun Suk ; Kwon, Oh Sang ; Kim, Ju Hyun ; Yeon, Jong Eun ; Song, Jin Won ; Byun, Kwan Soo ; Lee, Chang Hong. / Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy. In: Taehan Kan Hakhoe chi = The Korean journal of hepatology. 2002 ; Vol. 8, No. 4. pp. 397-404.
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abstract = "BACKGROUND/AIMS: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. METHODS: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. RESULTS: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0{\%} and 7{\%} in the HBeAg-negative group, they were 12{\%} and 39{\%} in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3{\%} vs 5.1{\%}; p<0.01). CONCLUSIONS: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.",
author = "Chang, {Yun Jung} and Yim, {Jeong Yoon} and Cho, {Nam Young} and Choi, {Chang Won} and Baek, {Soo Jung} and Ahn, {Soo Hyun} and Choi, {Do Won} and Kwon, {Yong Dae} and Kim, {Sun Suk} and Kwon, {Oh Sang} and Kim, {Ju Hyun} and Yeon, {Jong Eun} and Song, {Jin Won} and Byun, {Kwan Soo} and Lee, {Chang Hong}",
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T1 - Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy

AU - Chang, Yun Jung

AU - Yim, Jeong Yoon

AU - Cho, Nam Young

AU - Choi, Chang Won

AU - Baek, Soo Jung

AU - Ahn, Soo Hyun

AU - Choi, Do Won

AU - Kwon, Yong Dae

AU - Kim, Sun Suk

AU - Kwon, Oh Sang

AU - Kim, Ju Hyun

AU - Yeon, Jong Eun

AU - Song, Jin Won

AU - Byun, Kwan Soo

AU - Lee, Chang Hong

PY - 2002/12/1

Y1 - 2002/12/1

N2 - BACKGROUND/AIMS: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. METHODS: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. RESULTS: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01). CONCLUSIONS: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.

AB - BACKGROUND/AIMS: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. METHODS: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. RESULTS: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01). CONCLUSIONS: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.

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