Shin Jung Woo, Chung Young-Hwa, Choi Min Hee, Kim Jeong A, Ryu Soo Hyung, Jang Myoung Kuk, Kim In Sook, Park Neung Hwa, Lee Han Chu, Lee Yung Sang, Suh Dong Jin
Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-dong Songpa-ku, 138-040 Seoul, Korea.
J Gastroenterol Hepatol. 2005 Jun;20(6):844-9. doi: 10.1111/j.1440-1746.2005.03824.x.
Frequent viral breakthroughs limit the usefulness of lamivudine in the treatment of chronic hepatitis B (CHB). The purpose of the present study was to evaluate the effects of precore stop codon mutation (G to A mutation at nucleotide 1896; A(1896)) of hepatitis B virus (HBV) on the occurrence of viral breakthrough following lamivudine therapy.
Among 260 consecutive CHB patients treated with lamivudine for >12 months, 231 patients whose pretreatment sera were available were tested for A(1896) variant of HBV using direct sequencing.
Between patients with A(1896) variant (n = 74) and those without it (n = 157), there was no difference in age, gender, serum alanine aminotransferase (ALT) level, the duration of therapy and prevalence of core promoter mutants. Serum hepatitis B e antigen (HBeAg) positivity and HBV-DNA level were lower (P = 0.00 and P = 0.01) and liver cirrhosis was more commonly associated in patients with A(1896) variant mutant compared with those without it. In univariate analysis, viral breakthrough was more frequent in HBeAg-positive patients (P = 0.03) and in those with high serum HBV-DNA level (P = 0.01) as well as in those without A(1896) variant (P = 0.01). However, in multivariate analysis, the absence of A(1896) variant (P = 0.02) and high serum HBV-DNA level (P = 0.03) were independent factors for viral breakthrough following lamivudine therapy. The cumulative viral breakthrough rates at 1 and 2 years were much lower in patients with A(1896) variant compared with those without it (P = 0.01).
The stop codon mutation at the precore region of HBV in addition to low serum HBV-DNA level may be associated with low breakthrough rate following lamivudine therapy.
频繁的病毒突破限制了拉米夫定在慢性乙型肝炎（CHB）治疗中的有效性。本研究的目的是评估乙肝病毒（HBV）前核心区终止密码子突变（核苷酸1896处G突变为A；A(1896)）对拉米夫定治疗后病毒突破发生情况的影响。
在260例连续接受拉米夫定治疗超过12个月的CHB患者中，对231例有治疗前血清样本的患者，采用直接测序法检测HBV的A(1896)变异体。
在有A(1896)变异体的患者（n = 74）和无该变异体的患者（n = 157）之间，年龄、性别、血清丙氨酸氨基转移酶（ALT）水平、治疗持续时间和核心启动子突变的发生率无差异。与无A(1896)变异体的患者相比，有A(1896)变异体的患者血清乙肝e抗原（HBeAg）阳性率和HBV-DNA水平较低（P = 0.00和P = 0.01），且肝硬化更为常见。单因素分析显示，HBeAg阳性患者（P = 0.03）、血清HBV-DNA水平高的患者（P = 0.01）以及无A(1896)变异体的患者（P = 0.01）病毒突破更为频繁。然而，多因素分析显示，无A(1896)变异体（P = 0.02）和血清HBV-DNA水平高（P = 0.03）是拉米夫定治疗后病毒突破的独立因素。有A(1896)变异体的患者1年和2年的累积病毒突破率远低于无该变异体的患者（P = 0.01）。
HBV前核心区的终止密码子突变以及低血清HBV-DNA水平可能与拉米夫定治疗后低突破率相关。
