대한간학회 학술연구기금 지원과제 결과 보고

Optimal management of clevudine resistant chronic ; A multicenter cohort study

Hyung Joon Yim1,11, Eun Young Cho2,11, Eileen L. Yoon1,11, Yeon Seok Seo1,11, Ji Hoon Kim1,11, Hong Soo Kim3,11, Se Hwan Lee3,11, Sang Hoon Ahn4,11, Sook-Hyang Jeong5,11, Jin-Wook Kim5,11, Jeong Il Lee6,11, Jin Woo Lee6,11, In Hee Kim7,11, Hyung Soo Kim8,11, Joong Min Lee9,11, Bo Hyun Kim10,11, Sang Jong Park10,11, Young Min Park10,11, and *Sung Gyu Hwang9,11

Department of Internal Medicine, School of Medicine, 1Korea University, 2Wonkwang University, 3Soon Chun Hyang University, 4Yonsei University, 5Seoul National University, 6Inha University, 7Chonbuk National University, 8Hallym University, 9CHA Medical College, and 10Bundang Jesaeng Hospital, 11Antiviral Resistance Study Group.

Background: Although, clevudine is a potent for the management of chronic hepatitis B (CHB), emergence of drug resistance is the one of the major drawback. Still, optimal management of clevudine resistance needs to be elucidated.

Methods: On March 2010, we retrospectively reviewed the medical records and registered clevudine-resistant CHB patients to the cohort. Prospective follow-ups were done until March 2011. Antiviral efficacy of each rescue regimen was evaluated.

Results: A total of 118 patients were registered. Patients received (n=15, group1), adefovir plus clevudine (n=23, group2), adefovir plus (n=37, group3), or (n=43, group4) over 48 weeks. Baseline characteristics were not different between the groups. Mean HBV DNA were 6.4, 5.8, 5.3, 5.7 log copies/mL at baseline (p=0.077), 4.9, 2.6, 3.3, 3.3 log copies/mL at week 24 (p=0.003), and 3.4, 2.8, 3.4, 3.2 log copies/mL at week 48 (p=0.816), respectively. Mean degrees of HBV DNA reduction from baseline were -1.7, -3.2, -2.0, -2.4 log copies/mL at week 24 (p=0.017), -3.2, -3.0, -1.9, -2.7 log copies/mL at week 48 (p=0.401), respectively. HBV DNA undetectability (<60 IU/mL) was 0%, 33.3%, 16.7%, 22.9% at week 24 (p=0.131) and 30.3%, 31.3%, 23.1%, 31.3% (p=0.95), respectively. HBV DNA reduced significantly from baseline to week 24 and week 48 in all groups (p<0.05, Wilcoxon signed rank test). Levels of mean ALT and rate of ALT normalization were not statistically different between the groups through 48 weeks. HBeAg loss (22.2%, 14.3%, 15.8%, 16.0%, respectively, p=0.964) and HBeAg seroconversion (11.1%, 10.0%, 20.0%, 14.3%, respectively, p=0.920) rates were not different, either.

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Elevations of CPK (>3 × ULN) were noted in 2 patient from group2 and 1 patient from group3.

Conclusions: Although adefovir monotherapy showed slow decline of HBV DNA until week 24, HBV DNA significantly decreased in most of groups through 48 weeks of rescue therapy.

Keyword: Clevudine, lamivudine, adefovir, entecavir, resistance

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