Uzun Yusuf, Bozkaya Hakan, Erden Esra, Cinar Kubilay, Idilman Ramazan, Yurdaydin Cihan, Uzunalimoglu Ozden
Department of Gastroenterology, Faculty of Medicine, Karadeniz Technical University, Blok 30 Daire 11, 61080 Trabzon, Turkey.
J Gastroenterol Hepatol. 2006 Jun;21(6):977-81. doi: 10.1111/j.1440-1746.2006.04263.x.
In hepatitis B early antigen (HBeAg)-negative patients, response predictors to current treatment regimens are not well known. Hepatocyte cell cycle may influence hepatitis B virus (HBV) replication and hepatitis B core antigen (HBcAg) expression, which is a major target for antiviral immune response. The aim of the present paper was to evaluate the role of HBcAg expression in liver tissue and the rate of hepatocyte proliferation in response to antiviral treatment in chronic hepatitis B.
A total of 33 chronic hepatitis B patients (nine HBeAg positive, 24 HBeAg negative) treated with either lamivudine and interferon combined or lamivudine alone were included. Liver expressions of proliferating cell nuclear antigen (PCNA) and HBcAg were immunohistochemically determined. The HBV-DNA levels were measured by a hybrid capture assay. Complete response was defined as alanine aminotransferase (ALT) normalization and HBV-DNA negativity.
At the end of treatment, 23 patients (67.7%) were responders (12 of 23 were sustained responders), while 10 (33.3%) were non-responders. Age, sex, ALT, HBV-DNA levels, HBeAg status, histological activity, fibrosis scores and PCNA labeling index were similar in responders versus non-responders at baseline. The number of patients with positive HBcAg staining was lower in responders compared to non-responders at the end of treatment (17.4% vs 80%, respectively, P < 0.001), although a similar number of sustained responders and non-responders had positive HBcAg staining.
Absence or a low level of HBcAg expression may predict the end of treatment response to current therapies, especially in HBeAg (-) patients. The PCNA determination does not predict treatment response.
在乙肝e抗原(HBeAg)阴性患者中,目前治疗方案的反应预测指标尚不清楚。肝细胞细胞周期可能影响乙肝病毒(HBV)复制及乙肝核心抗原(HBcAg)表达,而HBcAg是抗病毒免疫反应的主要靶点。本文旨在评估肝组织中HBcAg表达及肝细胞增殖率在慢性乙型肝炎抗病毒治疗反应中的作用。
纳入33例接受拉米夫定与干扰素联合治疗或单用拉米夫定治疗的慢性乙型肝炎患者(9例HBeAg阳性,24例HBeAg阴性)。采用免疫组织化学方法测定增殖细胞核抗原(PCNA)和HBcAg在肝脏中的表达。采用杂交捕获法检测HBV-DNA水平。完全缓解定义为丙氨酸氨基转移酶(ALT)正常化且HBV-DNA阴性。
治疗结束时,23例患者(67.7%)有反应(23例中有12例为持续反应者),10例(33.3%)无反应。反应者与无反应者在基线时的年龄、性别、ALT、HBV-DNA水平、HBeAg状态、组织学活性、纤维化评分及PCNA标记指数相似。治疗结束时,反应者中HBcAg染色阳性的患者数量低于无反应者(分别为17.4%和80%,P<0.001),尽管持续反应者和无反应者中HBcAg染色阳性的数量相似。
HBcAg表达缺失或水平较低可能预示当前治疗的反应结局,尤其是在HBeAg(-)患者中。PCNA测定不能预测治疗反应。