라미부딘 투약 후 혈청 HBeAg 소실의 인자로서 투약 후 HBV DNA치
Change of HBV DNA Level as a Predictor of HBeAg Loss after Lamivudine Treatment
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배경/목적: 라미부딘은 만성 B형간염에서 안전하고 효과적인 치료제로 널리 사용되고 있으며 조기에 바이러스의 증식을 강력히 억제하는 약물로 알려져 있다. 라미부딘 치료 중 HBV DNA의 조기억제가 HBeAg 음전을 예측하는 인자로 작용하는지 알아보기 위해 본 연구를 시행하였다. 대상과 방법: 본 전향연구는 혈청 HBV DNA가 105 copies/ mL 이상, 혈청 AST 또는 ALT치가 정상의 두 배 이상인 환자 중 HBeAg 양성인 환자를 대상으로 하였으며 총 대상 환자 수는 74명(평균 연령은 37.1; 남/여, 51/23)이었다. 치료 전, 치료 1개월, 3개월, 6개월, 9개월, 12개월에 각각 HBV DNA치, AST/ALT치, HBeAg과 anti-HBe를 검사하였고 1년간 라미부딘 치료를 하였다. 치료 1년 내에 HBeAg이 소실된 군과 소실되지 않은 군으로 분류하여 HBV DNA치의 조기 억제가 HBeAg 소실에 관여하는지 분석하였다. HBV DNA의 측정은 민감도가 2×103 copies/mL인 HBV bDNA 정량법으로 검사하였다. 결과: 라미부딘 사용 1년 내에 HBeAg이 소실된 환자는 12명으로 전체의 16.2%였으며 9명에서 혈청전환이 동반되었다. HBeAg이 소실되는 데 걸린 시간은 평균 5.6개월(범위: 1-12개월)이었다. 단변량 분석에서 치료 후 3개월 HBV DNA 2×103 copies/mL 미만(P=0.008)과 치료 후 6개월 HBV DNA 2×103 copies/mL 미만(P= 0.011)이 HBeAg의 소실에 유의한 인자로 나타났다. 치료 전 HBV DNA치와 ALT치, 성별, 나이 및 간경변증 유무 등은 HBeAg의 소실에 영향을 주지 못하였다. 치료 후 3개월 HBV DNA치, 치료 후 6개월 HBV DNA치, 치료 전 AST치를 대상으로 다변량 분석(multivariate logistic regression)을 실시한 결과 치료 후 6개월 HBV DNA치(P=0.008, odds ratio=0.108)가 HBeAg의 소실에 유의한 인자로 나타났다. 결론: 라미부딘 치료 후 6개월 HBV DNA치(<2×103 copies/mL)가 치료 1년 이내 HBeAg의 소실에 관여하는 가장 중요한 인자로 생각된다.
Abstract
Backgroud/Aims: Lamivudine is an effective, safe therapeutic agent for the treatment of chronic hepatitis B. The aim of this study was to investigate whether early suppression of the viral load predicts HBeAg loss within 1 year during lamivudine therapy. Methods: This prospective study encompassed 74 patients (mean age: 37.1 years, male/female: 51/23) who were positive HBeAg, their AST or ALT levels were ≥2 times the upper limit of normal and their HBV DNA was ≥105 copies/mL. The patients received lamivudine 100 mg for 12 months with monitoring their HBV DNA, AST, ALT, HBeAg and anti-HBe, and all these tests were performed at pretreatment and 1, 3, 6, 9 and 12 months after treatment. The serum HBV DNA was measured by HBV branched DNA assay. Results: HBeAg loss was observed in 12 patients (16.2%), and 9 patients achieved anti-HBe seroconversion during up to 1 year of lamivudine therapy. The mean time to HBeAg loss was 5.6 months (range: 1-12 months). The posttreatment HBV DNA (<2,000 copies/mL) after 3 month (P=0.008) and 6 month (P=0.012)) were significant predictors of HBeAg loss after 1 year of lamivudine treatment on univariate analysis. Pretreatment HBV DNA, AST/ALT, gender, age and liver cirrhosis had no impact on HBeAg loss. The six-month posttreatment HBV DNA level <2,000 copies/mL was a significant predictor of HBeAg loss on multivariate analysis (P=0.008, odds ratio=0.108). Conclusion: We suggest that an HBV DNA level <2,000 copies/mL at 6 month after lamivudine therapy is the most important predictor of HBeAg loss during up to 1 year of lamivudine therapy.
참고문헌 (16)
- "A Study on the seropositivity of HBsAg among biennial health examinees: a nation-wide multicenter survey", 35, pp.129~135 (2002)
- "Hepatitis B viral markers of Korean adults in the late 1990s: Survey data of 70,347 health screenees", 33, pp.642~652 (1999)
- "3'-dideoxy-3'- thiacytidine as anti-hepatitis B virus agents", pp.22414~22420
- "A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group", 339, pp.61~68 (1998)
- "Effect of lamivudine in HBeAg- positive chronic hepatitis B: discordant effect on HBeAg and HBV DNA according to pretreatment ALT level", 11, pp.3346~3350 (2005)
- "Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B", 36, pp.186~194 (2002)
- "Correlation of hepatitis B virus load with loss of e antigen and emerging drug-resistant variants during lamivudine therapy", 65, pp.659~663 (2001)
- "Early virological response predicts outcome during extended lamivudine retreatment in patients with chronic hepatitis B who relapsed after initial HBeAg responses", 21, pp.384~391 (2006)
- "Current antiviral therapy for chronic hepatitis B", 19, pp.489~494 (2004)
- "Lamivudine as initial treatment for chronic hepatitis B in the United States", 341, pp.1256~1263 (1999)
- Kim JH, "Clinical outcomes of chronic hepatitis B patients with persistently detectable serum hepatitis B virus DNA during lamivudine therapy", 22, pp.1220~1225 (2007)
- Park HS, "Correlation of HBV DNA level and viral breakthrough during lamivudine therapy for chronic hepatitis B", 12, pp.173~183 (2006)
- Kweon YO, "Pretreatment ALT level and histologic activity as predictors of HBeAg loss in lamivudine treatment for chronic hepatitis B", 10, pp.31~41 (2004)
- Chien RN, "Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group", 30, pp.770~774 (1999)
- Knodell RG, "Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis", k(dell rg), pp.431~435
- Ronsin C, "Evaluation of the COBAS AmpliPrep-total nucleic acid isolation-COBAS TaqMan hepatitis B virus (HBV) quantitative test and comparison to the VERSANT HBV DNA 3.0 assay", 44, pp.1390~1399 (2006)