급성 악화를 보인 만성 B형 간염의 치료에 있어서 Lamivudine 즉시 투여의 적절성 = Adequacy of Immediate Lamivudine Trial for Chronic Hepatitis B Patients with Acute Exacerbation

국문 초록 (Abstract)

목적: 만성 B형 간염의 급성 악화시 즉시 라미부딘 치료를 하는 것이 합리적인지에 대해 이해가 부족한 바, 이들의 자연경과를 알아보고 라미부딘 투여군의 비교를 통해서 라미부딘 치료의 적절한 시점을 알아보고자 하였다. 대상과 방법: 2000년 3월부터 2003년 5월까지 본원에 내원한 만성 B형 간염 환자 중 혈중 HBV DNA 또는 HBeAg 양성, ALT>400 IU/L인 35명을 대상으로 혈청 HBV DNA, HBeAg, anti-HBe, ALT를 포함한 간기능 검사를 1-3개월 간격으로 측정하였으며 ALT가 재상승한 경우, 100 IU/L 이상시 라미부딘 100 ㎎을 매일 경구 투여하고, 무작위로 선출된 환자에게 내원 당시 즉시 라미부딘을 투여하고 상기의 방법으로 검사를 시행하여 라미부딘의 효과를 비교하였다. 결과: 내원 당시 혈청 ALT가 400 IU/L 이상의 소견을 보인 27명의 환자를 대상으로 항바이러스제를 투여하지 않고 경과 관찰을 시행하였으며 이중 5명의 환자에게서 평균 19개월 추적관찰중 정상 ALT, HBeAg의 음성, HBV DNA의 음성상태가 유지되었고(제1a군) 3명의 환자에서 ALT가 약간 상승하거나 정상이었지만 HBeAg의 자연 음전은 유도되지 않았다(제1b군). 반면, 19명의 환자에서는 평균 5개월 만에 ALT의 재상승 소견을 보여 라미부딘 치료를 시작하였다(제2군). 제1a군과 제2군 사이에서 혈청 HBV DNA의 중앙값은 각각 6.5 pg/mL과 518.1 pg/mL로 제1a군에서 현저히 낮았으며 HBV DNA가 20 pg/mL 이하였던 환자 7명 중 5명(71.4%)에서 자연음전이 유도되었다. 경과 관찰 중 재상승한 환자 19명 중 16명의 환자와 급성 악화로 내원 즉시 라미부딘을 투여한 환자 8명(제3군)을 비교한 결과, 제2군에서는 3군에 비해 치료시 혈청 ALT는 낮고 HBV DNA는 높았으며 첫 내원시보다 오히려 혈중 HBV DNA가 높은 상태에서 라미부딘 치료가 시작되었다. 양군 간의 라미부딘 치료 효과는 2군에서 56.3% (9/16)로 3군의 62.5% (5/8)와 차이가 없었다. 결론: 급성 악화를 동반한 만성 B형 간염 환자의 경우 내원 당시 혈중 HBV DNA가 현저히 낮은 경우는 HBeAg의 자연음전을 기대할 수 있으나, 대부분의 경우 라미부딘의 즉시 치료를 통한 HBeAg의 음전을 시도하는 것이 바람직하다고 생각된다.

다국어 초록 (Multilingual Abstract)

Background/Aims: It has been unclear whether immediate antiviral therapy or observation under the expectation of spontaneous inactivation of hepatitis B virus (HBV), is more appropriate for the treatment of chronic hepatitis B (CHB) with acute exacerbation. We intended to analyze the short-term natural course of CHB with acute exacerbation and evaluate the efficacy of lamivudine. Methods: We analyzed 35 CHB patients with acute exacerbation (positive HBV DNA or HBeAg and ALT>400 IU/L) between March 2000 and May 2003. We regularly checked serum HBV DNA, HBeAg and liver unction tests including ALT every 1 to 3 months. If ALT was above 100 IU/L during the follow-up period, patients were treated with 100 ㎎ lamivudine orally once a day. We compared the efficacy of lamivudine use between this group and the group provided with immediate lamivudine trial at their first visit. Results: 27 CHB patients with acute exacerbation were observed without immediate lamivudine trial. In 5 of these patients normal ALT, negative HBeAg and HBV DNA were maintained during 19 months (group la). Slightly elevated or normal ALT was maintained without HBeAg seroconversion in 3 patients (group 1b). However, serum ALT flared up above 100 IU/L in 19 patients within 5 months. So, lamivudine was tried on these patients (group 2). The serum HBV DNA was extremely low, being 6.5 pg/mL in group la compared to 518.1 pg/mL in group 2. Spontaneous inactivation of HBV was observed in 71.4% (5/7) of patients with HBV DNA less than 20 pg/mL at the first visit. ALT was lower and HBV DNA was higher in group 2 than the 8 patients who received immediate lamivudine trial at the first visit (group 3). The response rate of lamivudine was similar between group 2, 56.3% (9/16) and group 3, 62.5% (5/8). Conclusions: Spontaneous inactivation of HBV was expected in CHB with acute exacerbation and extremely low level of HBV DNA (less than 20 pg/mL) in a short term follow-up period. Immediate lamivudine therapy might be more appropriate in most CHB patients with acute exacerbation.(Korean J Hepatol 2004;10:22-30)

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