만성 B형간염에서 클레부딘의 48주 치료 효과
Efficacy of 48-week clevudine therapy for chronic hepatitis B
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목적: 클레부딘은 피리미딘 유사체로 실험실 및 동물실험에서 B형간염바이러스에 대해 강력한 억제 효과를 보여주었고, 만성 B형간염 환자를 대상으로 24주간 투여 효과를 평가한 3상 시험에서 강력하고 지속적인 항바이러스 효과를 나타내었다. 이번 연구에서는 48주 이상 클레부딘을 투여받은 만성 B형간염 환자 대상으로 클레부딘의 항바이러스 효과 및 바이러스 내성의 발생에 대해 알아보고자 하였다. 대상과 방법: 48주 이상 클레부딘을 투여받은 만성 B형간염 환자의 의무기록을 후향적으로 분석하였다. 3년 이내에 라미부딘 치료를 받은 적이 있는 환자는 제외하였다. 혈청 HBV DNA는 PCR hybridization 방법(검출 한계 316 copies/ mL)으로 측정하였다. 투여 24주와 48주째 혈청 HBV DNA, 혈청생화학검사 수치, 바이러스표지자 등을 분석하였다. 바이러스 돌파 현상 및 항바이러스 약제에 대한 내성의 발생 여부도 알아보았다. 결과: 총 74명의 만성 B형간염 환자가 포함되었으며(평균 연령 44세, 남:여=54:20, HBeAg 양성 환자 47명, HBeAg 음성 환자 27명), 이 중 10명은 라미부딘 치료를 받은 적이 있었다. 치료 전 혈청 HBV DNA 수치의 중앙값은 6.49 log10 copies/mL였다. 치료 48주째 혈청 HBV DNA 수치 감소폭의 중앙값은 전체 환자군에서 -4.34 log10 copies/mL, HBeAg 양성군에서 -4.84 log10 copies/mL, HBeAg 음성군에서 -3.74 log10 copies/mL였다. 치료 48주째 혈청 HBV DNA는 전체 환자 중 83.3%에서 검출되지 않았으며, 음전율은 HBeAg 양성군의 경우 76.6%, HBeAg 음성군의 경우 96.3%였다. 치료 48주째 84.7%의 환자에서 정상 혈청 ALT 수치를 보였다. 치료 48주째 두 명에서 바이러스 돌파 현상이 발생하였으며, 이전의 라미부딘 치료력과 간경변증의 존재가 내성 발생과 연관이 있었다. 결론: 만성 B형간염 환자를 대상으로 한 48주간의 클레부딘 치료는 효과적이었다. 그러나 이전 라미부딘 치료 경험자나 간경변이 동반된 경우 클레부딘에 대한 내성 발생의 위험이 증가한다.
Abstract
Background/Aims: Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB. Methods: Data on patients with CHB and detectable serum hepatitis B virus (HBV) DNA who were treated with clevudine for 48 weeks or longer were collected retrospectively for this study. Patients who had taken lamivudine within the 3 years prior to this study were excluded. Serum HBV DNA was measured by polymerase chain reaction hybridization (lower detection limit= 316 copies/mL). Serum HBV DNA and biochemical data were analyzed at weeks 24 and 48. Developments of viral breakthrough and resistance to the antiviral drug were also monitored. Results: Data from 74 patients (mean age 44 years; M:F=54:20; HBeAg-positive, 47; HBeAg-negative, 27) were included in this study. Ten patients had experienced previous lamivudine treatment. Median HBV DNA at baseline was 6.49 log10 copies/mL. Median serum HBV DNA reductions from baseline at week 48 were -4.34 log10 copies/mL (HBeAg-positive, -4.84 log10 copies/mL; HBeAg-negative, -3.74 log10 copies/mL). At week 48, serum HBV DNA was not detected in 83.8% of the patients (HBeAg-positive, 76.6%; HBeAg-negative, 96.3%). Normalization of serum alanine aminotransferase levels was achieved in 84.7% of the patients. Viral breakthrough and antiviral resistance developed in two patients at week 48. The development of antiviral resistance was associated with the presence of previous lamivudine treatment and cirrhosis. Conclusion: A 48-week course of clevudine therapy was highly effective in patients with CHB. The risk of development of resistance to clevudine was increased in patients with previous exposure to lamivudine and cirrhosis.
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