라미부딘 치료 후 라미부딘 내성을 보이지 않는 환자에서 엔테카비어 효과
Effect of Entecavir in Patients Who Lack Lamivudine Resistance after Lamivudine Treatment for Chronic Hepatitis B
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목적: 라미부딘 치료 후 라미부딘 내성을 보이지 않는 만성 B형 간염 환자에서 엔테카비어 효과를 평가하기 위해 본연구를 시행하였다. 방법: 엔테카비어 0.5 mg을 6개월 이상 투약하였던 총350명을 대상으로 엔테카비어 초치료군과 라미부딘 치료 경험이 있는 군으로 나누어 분석하였다. 추가적으로 라미부딘경험군을 라미부딘 투약 중단과 엔테카비어 투약 시작 사이의 간격을 기준으로 엔테카비어 전환군(43명)과 엔테카비어재치료군(44명)으로 나누어 분석하였다. 결과: 초치료군은 263명, 라미부딘 경험군은 87명이었고,평균 나이, 남녀비, 간경변증의 비율, HBe항원 양성률(63.1%vs. 51.7%)은 양 군에서 차이가 없었으나, AST치(186.6 ± 17.6IU/L vs. 85.1 ± 11.9 IU/L)와 ALT치(230.9 ± 23.0 IU/L vs. 104.5 ± 19.3 IU/L)는 초치료군에서 라미부딘 경험군보다 더높았다(p < 0.05). HBV DNA치에 따라 초치료군과 라미부딘경험군의 분포를 비교했을 때 HBV DNA치가 2 × 104 IU/mL 미만인 경우 라미부딘 경험군의 비율이 더 높았으며 2 × 104-107IU/mL, 107 IU/mL 이상인 경우 초치료군의 비율이 더 높았다(7.6% vs. 43.7%, 47.9% vs. 34.5%, 44.5% vs. 21.8% for < 2 ×104 IU/mL, 2 × 104-107 IU/mL, ≥ 107 IU/mL) (Table 1). 엔테카비어 치료 후 초치료군과 라미부딘 경험군 사이에 HBV DNA 음전율(6개월, 78.8% vs. 85.7%, p = 0.205; 12개월, 84.0%vs. 85.9%, p = 0.844; 18개월, 82.1% vs. 82.5%, p = 1.000),HBe항원 소실률(24.7% vs. 24.4%, p = 0.170) 및 혈청 전환율(13.3% vs. 11.1%, p = 0.159), 6개월 후 ALT치의 정상화율(84.2% vs. 76.7%, p = 0.142), 바이러스 돌파율(4.6% vs. 12.6%,p = 0.134)과 엔테카비어-유전자형 내성 발생률(0.4% vs. 3.4%,p = 0.128) 모두 차이가 없었다. 엔테카비어 전환군과 재치료군을 비교했을 때 엔테카비어 치료 효과는 차이가 없었다. 결론: 라미부딘 내성이 없는 라미부딘 경험군에서 엔테카비어 치료 효과를 초치료군과 비교했을 때 그 차이가 없고엔테카비어 치료가 연속적이지 않아도 그 효과는 달라지지않을 것으로 생각한다.
Abstract
Background/Aims: The effect of entecavir (ETV) in treatment-naïve chronic hepatitis B (CHB) is well established. This study aimed to assess the efficacy of ETV treatment at 0.5 mg/day in ETV-switch and ETV-retreatment groups of CHB patients without lamivudine (LMV)-resistance from LMV monotherapy. Methods: Study subjects included 350 CHB patients who had been treated with 0.5 mg/day of ETV for at least 6 months. Patients were divided into two groups: an LMV-naïve group (n = 263) and an LMV-experienced group (n = 87). The LMV-experienced group was further subdivided into an ETV-switch group (n = 43) and an ETV-retreatment group (n = 44) defined by the period between stopping LMV and restarting ETV. Results: There were no significant differences in mean age, sex ratio, prevalence of liver cirrhosis and hepatitis B e antigen (HBeAg) positivity between the LMV-naïve and -experienced groups. However, the LMV-naïve group had higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and a shorter ETV treatment duration than the LMV-experienced group. There were also distributional differences in the hepatitis B virus (HBV) DNA levels of LMV-naïve and -experienced patients prior to ETV treatment. After ETV treatment, there were no significant differences between the two groups in the rates of undetectable HBV DNA at 6, 12 and 18 months; HBeAg loss and seroconversion; normalization of ALT; virologic breakthrough; and ETV-genotypic resistance. Lastly, the effect of ETV did not differ between the ETV-switch and -retreatment groups. Conclusions: The effect of ETV in the LMV-experienced group without LMV-resistance did not differ from that in the LMV-naïve group. Furthermore, there was no difference in the effect of ETV between the ETV-switch and -retreatment groups.
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