Manning Diarmuid S, Sheehan Katherine M, Byrne Michael F, Kay Elaine W, Murray Frank E
Department of Clinical Pharmacology/Gastroenterology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland.
J Gastroenterol Hepatol. 2007 Oct;22(10):1633-7. doi: 10.1111/j.1440-1746.2007.04869.x.
Cyclooxygenase-2 (COX-2), a target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), is upregulated in chronic hepatitis B and may have a role in hepatocellular carcinoma. Little is known about the expression of COX-2 in chronic hepatitis C (HCV) infection. The aim the present study was to evaluate the extent of COX-2 expression in liver biopsies in patients with HCV infection and to determine the effect of treatment with interferon alpha (IFN).
Percutaneous liver biopsy specimens were retrieved. Following formalin fixation and paraffin embedding, the biopsies were histologically evaluated for inflammation and fibrosis. The extent of COX-2 expression was measured by the avidin biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to the number of hepatocytes expressing COX-2. Data were analyzed using Student's t-test.
Liver biopsies from 10 patients before and after treatment with IFN were obtained and compared with nine normal liver biopsies. All of the liver biopsies showed some COX-2 expression. COX-2 expression was confined to hepatocytes and bile duct epithelium and was not detected in vascular endothelium or inflammatory cells. The extent of COX-2 expression was greater in hepatitis C infected liver biopsies than in normal biopsies. Following treatment with IFN, there was a greater than threefold reduction in COX-2 expression (P < 0.01). This result was independent of the sustained virological response.
In this small pilot study we have shown that COX-2 is overexpressed in liver biopsies infected with HCV and COX-2 expression is reduced following treatment with IFN.
环氧合酶-2（COX-2）是阿司匹林及其他非甾体抗炎药的作用靶点，在慢性乙型肝炎中表达上调，可能在肝细胞癌的发生中起作用。关于COX-2在慢性丙型肝炎（HCV）感染中的表达情况知之甚少。本研究的目的是评估HCV感染患者肝活检中COX-2的表达程度，并确定α干扰素（IFN）治疗的效果。
获取经皮肝活检标本。经福尔马林固定和石蜡包埋后，对活检组织进行组织学炎症和纤维化评估。采用抗生物素蛋白-生物素免疫组化技术，使用单克隆COX-2抗体测量COX-2的表达程度。根据表达COX-2的肝细胞数量对COX-2表达程度进行分级。数据采用学生t检验进行分析。
获取了10例患者IFN治疗前后的肝活检标本，并与9例正常肝活检标本进行比较。所有肝活检标本均显示有一定程度的COX-2表达。COX-2表达局限于肝细胞和胆管上皮，在血管内皮或炎症细胞中未检测到。HCV感染的肝活检标本中COX-2的表达程度高于正常活检标本。IFN治疗后，COX-2表达降低了三倍多（P < 0.01）。这一结果与持续病毒学应答无关。
在这项小型初步研究中，我们发现COX-2在HCV感染的肝活检标本中过度表达，IFN治疗后COX-2表达降低。
