만성 B형간염 환자에 대한 초치료제로서 엔테카비어의 항바이러스 효과와 그 예측인자
Efficacy and predictors of the virologic response to entecavir therapy in nucleoside-naïve patients with chronic hepatitis B
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목적: 항바이러스 약제에 대한 치료 경험이 없는 국내 만성 B형간염 환자의 초치료제로서 엔테카비어의 치료 효과와 치료 반응의 예측인자를 알아보고자 하였다. 대상 및 방법: 2007년 2월부터 2009년 8월까지 본원에 내원한 만성 B형간염 환자 중 과거 항바이러스 약제 사용력이 없으며 24주 이상 엔테카비어를 복용한 160명을 대상으로 후향적으로 연구하였다. 엔테카비어 투여 중 혈청 HBV DNA의 소실(2000 copies/mL 미만)을 바이러스 반응으로, 혈청 ALT의 정상화를 생화학적 반응으로 정의하였고, 혈청 HBeAg 소실과 HBeAg 혈청전환을 평가하였다. 바이러스 돌파는 HBV DNA치가 2번의 연속된 검사에서 이전 검사 결과보다 1 log10 이상 증가하였을 경우로 정의하였다. 결과: 총 160명의 환자 중, 남자는 85명(53.1%), HBeAg 양성인 환자는 85명(53.1%), 간경변이 동반된 환자는 70명(43.8%)이었고, 치료 전 혈청 ALT의 중앙값은 99 IU/L, 혈청 HBV DNA의 중앙값은 7.57 log10 copies/mL였다. 평균 58.8주 동안 추적관찰하였다. 누적 바이러스 반응률은 12주에 37.5%, 24주에 68.1%, 48주에 87.4%, 72주에 95.8%였고, 누적 생화학적 반응률은 12주에 40.0%, 24주에 66.2%, 48주에 84.5%, 72주에 92.7%였다. 누적 HBeAg 소실률은 12주에 10.6%, 24주에 18.8%, 48주에 27.0%, 72주에 34.5%였고, 누적 HBeAg 혈청전환율은 12주에 3.5%, 24주에 7.1%, 48주에 9.0%, 72주에 13.2%였다. 일차 치료 실패에 해당하는 환자나 바이러스 돌파 현상을 보인 환자는 없었다. 바이러스 반응과 관련된 유의한 예측인자는 치료 전 HBeAg이 음성, HBV DNA치의 상용로그 변환값이 8 미만인 경우였다. 결론:엔테카비어 치료는 국내의 항바이러스제 치료 경험이 없는 만성 B형간염 환자에서 강력한 항바이러스 효과를 보였으며, 바이러스 반응의 예측인자는 치료 시작 전 HBeAg의 유무, HBV DNA 값이다. 향후 장기간의 치료 성적에 대한 연구가 필요하다.
Abstract
Background/Aims: The aim of this study was to elucidate the antiviral efficacy and the predictors of entecavir treatment in nucleoside-naïve chronic hepatitis B patients. Methods: A total of 160 patients treated with entecavir (0.5 mg daily) for at least 24 weeks were consecutively enrolled. The virologic response (HBV DNA<2,000 copies/mL), biochemical response (ALT≤ upper limit of normal), and virologic breakthrough (>1 log10 copies/mL increase in HBV DNA level above nadir on two consecutive occasions) were retrospectively analyzed. Results: The mean follow-up duration was 58.8 weeks, and 85 patients (53.1%) showed HBeAg positivity. The median pretreatment levels of serum ALT and HBV DNA were 99 IU/L and 7.6 log10 copies/mL, respectively. The cumulative rates at 12, 24, 48, and 72 weeks were 37.5%, 68.1%, 87.4%, and 95.8%, respectively, for the virologic response; 40.0%, 66.2%, 84.5%, and 92.7% for the biochemical response; 10.6%, 18.8%, 27.0%, and 34.5% for HBeAg loss; and 3.5%, 7.1%, 9.0%, and 13.2% for HBeAg seroconversion. There was no case of virologic breakthrough. An absence of HBeAg and a low serum HBV DNA level (<8 log10 copies/mL) at baseline were significant predictors of the virologic response in a multivariate analysis (P<0.01). Conclusions: Entecavir therapy showed excellent efficacy in nucleoside-naïve chronic hepatitis B patients. The predictors of a virologic response were an absence of HBeAg and a low baseline HBV DNA level.
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