초치료 만성 B형간염 환자에서 엔테카비어 치료반응 및 관련 인자
Clinical efficacy of entecavir therapy and factors associated with treatment response in naïve chronic hepatitis B patients
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
목적: 엔테카비어는 만성 B형간염의 초치료 환자에서 강력한 항바이러스 효과 및 낮은 내성률이 보고되고 있다. 본 연구에서는 단일 기관에서 경험한 엔테카비어의 혈청, 생화학, 바이러스반응을 관찰하고 엔테카비어의 치료반응과 연관된 인자를 규명하고자 하였다. 대상과 방법: 12개월 이상 1일 1회 0.5 mg의 엔테카비어를 경구 투여받은 114명의 만성 B형간염 환자를 대상으로 하였다. 초기바이러스반응은 치료 3개월 후 혈청 HBV DNA가 2,000 copies/mL 미만으로 감소한 경우로 정의하였다. 결과: 엔테카비어 투여 후 혈청 ALT값의 정상화는 치료 6개월, 12개월, 24개월에 각각 76명(68.5%), 85명(74.6%), 62명(81.6%)에서, HBV DNA PCR 음전은 각각 50명(43.9%), 81명(71.1%), 65명(85.5%)에서 관찰되었다. HBeAg 혈청소실은 6개월에 17명(36.2%), 12개월에 27명(43.5%), 24개월에 22명(56.4%), 혈청전환은 각각 8명(12.9%), 9명(14.5%), 6명(15.4%)에서 관찰되었다. HBV DNA PCR 음전을 예측할 수 인자는 단변량 분석에서 HBeAg 유무, 치료 전 혈청 AST치, 혈청 HBV DNA치, 초기바이러스반응 유무였고, 다변량 분석에서 초기바이러스반응이 독립적인 인자였다[P< 0.001, OR=7.286(2.663～19.932)]. HBeAg의 혈청소실은 혈청 알부민치와 혈소판 수치가 낮은 경우, 혈청 AST치가 높은 경우, 간경변을 동반한 경우와 초기바이러스반응이 있는 경우에 빈번하게 발생하였고, 혈청 알부민[P=0.041, OR=0.232(0.057～0.945)]치와 초기바이러스반응[P=0.005, OR=7.017 (1.799～27.378)]이 독립적인 예측인자였다. 결론: 엔테카비어는 만성 B형간염의 초치료 환자에서 우수한 치료반응을 보였으며, 치료 3개월째 초기바이러스반응은 HBV DNA 음전 및 HBeAg 소실의 독립적 예측인자였다.
Abstract
Background/Aims: Entecavir is a potent and selective guanosine analogue that has demonstrated a significant antiviral efficacy against hepatitis B virus (HBV). The aim of this study was to characterize the response to entecavir and to examine the factors affecting that response. Methods: We administered 0.5 mg of entecavir once daily for more than 12 months to 114 naive chronic hepatitis B (CHB) patients. We measured the levels of liver enzymes, serological markers, and serum HBV DNA at 3-month interval. Results: Normalization of serum alanine aminotransferase levels was observed in 68.5% (76/114), 74.6% (85/114), and 81.6% (62/76) of patients after 6, 12, and 24 months of therapy, respectively. HBV DNA levels of <50 copies/mL (as evaluated by polymerase chain reaction) were observed in 43.9% (50/114), 71.1% (81/114), and 85.5% (65/76) of patients after 6, 12, and 24 months, respectively. Viral breakthrough was not observed. The rates of HBeAg loss and seroconversion were 43.5% (27/62) and 14.5% (9/62), respectively, after 12 months of therapy, and 56.4% (22/39) and 15.4% (6/39) after 24 months. The independent factor associated with PCR negativity was early virologic response (EVR; HBV DNA <2,000 copies/mL after 3 months of therapy, P<0.001). The independent factors predicting HBeAg loss were found to be serum albumin levels (P=0.041) and EVR (P=0.005). Conclusions: Entecavir induced excellent biochemical and virologic responses in naive CHB patients. EVR was an independent factor for predicting HBV PCR negativity and HBeAg loss.
참고문헌 (26)
- Perrillo RP, "Chronic hepatitis B: a critical appraisal of current approaches to therapy", Clin Gastroenterol Hepatol, 4, pp.233~248 (2006)
- Iloeje UH, "Risk Evaluation of Viral load Elevation and Associated Liver Disease", Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load, 2006, pp.130, 678~686
- Chen CJ, "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level", JAMA, 295, pp.65~73 (2006)
- Chang TT, "A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B", N Engl J Med, 354, pp.1001~1010 (2006)
- Leung N, "Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients with chronic hepatitis B: a randomized international study of entecavir versus adefovir", Hepatology, 49, pp.72~79 (2009)
- Tenney DJ, "Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside- naive patients is rare through 5 years of therapy", Hepatology, 49, pp.1503~1514 (2009)
- Lok AS, "Long-term safety of lamivudine treatment in patients with chronic hepatitis B", Gastroenterology, 125, pp.1714~1722 (2003)
- Lee KS, "Guideline Committee of the Korean Association for the Study of the Liver. Management of chronic hepatitis B", Korean J Hepatol, 13, pp.447~488 (2007)
- Sum SS, "Comparison of the COBAS TaqMan HBV test with the COBAS Amplicor monitor test for measurement of hepatitis B virus DNA in serum", J Med Virol, 77, pp.486~490 (2005)
- Bedossa P, "An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group", Hepatology, 24, pp.289~293 (1996)
- Chang TT, "Results of up to 2 years of entecavir vs lamivudine therapy in nucleoside-naive HBeAg-positive patients with chronic hepatitis B", J Viral Hepat, 16, pp.784~789 (2009)
- Kobashi H, "Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan", J Gastroenterol Hepatol, 24, pp.255~261 (2009)
- "Korean J Hepatol", 2009, S42~
- Lai CL, "Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B", N Engl J Med, 354, pp.1011~1020 (2006)
- Janssen HL, "Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomized trial", Lancet, 365, pp.123~129 (2005)
- Perrillo RP, "A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group", N Engl J Med, 323, pp.295~301 (1990)
- Lok AS, "A controlled trial of interferon with or without prednisone priming for chronic hepatitis B", Gastroenterology, 102, pp.2091~2097 (1992)
- Tseng TC, "A higher alanine aminotransferase level correlates with earlier hepatitis B e antigen seroconversion in lamivudine-treated chronic hepatitis B patients", Liver Int, 28, pp.1034~1041 (2008)
- Westland C, "Hepatitis B virus genotypes and virologic response in 694 patients in phase III studies of adefovir dipivoxil1", Gastroenterology, 125, pp.107~116 (2003)
- Fung SK, "Virologic response and resistance to adefovir in patients with chronic hepatitis B", J Hepatol, 44, pp.283~290 (2006)
- "Gastroenterology", 2005, A742~
- Wai CT, "A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C", Hepatology, 38, pp.518~526 (2003)
- Kamimoto Y, "Plasma clearance of intravenously injected aspartate aminotransferase isozymes: evidence for preferential uptake by sinusoidal liver cells", Hepatology, 5, pp.367~375 (1985)
- Okuda M, "Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein", Gastroenterology, 122, pp.366~375 (2002)
- Nalpas B, "Serum activity of mitochondrial aspartate aminotransferase: a sensitive marker of alcoholism with or without alcoholic hepatitis", Hepatology, 4, pp.893~896 (1984)
- Lau GK, "Impact of early viral kinetics on T-cell reactivity during antiviral therapy in chronic hepatitis B", Antivir Ther, 12, pp.705~718 (2007)