Analysis of the mechanism of liver damage and carcinogenesis in patients with chronic hepatitis C virus infection.

在丙型肝炎病毒（HCV）感染的肝脏中，B7/BB-1在肝细胞的胞浆中强烈表达。B7/BB-1阳性细胞伴随肝脏浸润淋巴细胞，并在HCV核心抗原和HLA I类阳性细胞附近检测到。B7/BB-1表达与病毒性肝炎活动性密切相关。这些发现表明，B7/BB-1表达的肝细胞可能是由HCV感染诱导，并可能触发CTL的产生和激活，这可能会导致损害HCV感染的HLA I类表达的肝细胞。为探讨干扰素治疗后肝癌发生的危险因素及肝癌的发生率，对1022例慢性丙型肝炎患者进行了13-97个月的超声随访。短暂应答者HCC的累积发生率与持续应答者几乎相等，而无应答者HCC的累积发生率显著高于持续应答者和短暂应答者。的 关于我们 持续应答者、短暂应答者和无应答者的HCC 7年累积发病率估计分别为4.3%、4.7%和26.1%。考克斯回归分析显示，干扰素治疗后肝癌高危人群多为无应答者、老年人和男性，针对HCVRNA的锤头状核酶切割靶HCVRNA，对病毒翻译有明显抑制作用，提示核酶介导的HCVRNA切割可能成为治疗HCV感染的一种新策略。与未转染B7 - 1的肝癌细胞相比，转染B7 -1的肝癌细胞在体外可诱导细胞免疫活性，表明体内或体外转染B7-1的肝癌细胞可诱导抗肝癌的免疫反应，转染B7 -1的肝癌细胞在同系BALB/c nu/nu小鼠体内的肿瘤生长速度与野生型肝癌细胞一样快。而B7-1转染的肝癌细胞在同系BALB/c小鼠体内的肿瘤生长较野生型肝癌细胞明显受到抑制，提示B7 - 1转染的肝癌细胞在体内可诱导抗肝癌免疫。因此，B7-1基因转染肝癌细胞有可能成为肝癌基因治疗的候选细胞之一，为阐明慢性HCV感染肝损害的机制和提高治疗效果提供了新的思路。少

In hepatitis C virus (HCV)-infected liver, B7/BB-1 was strongly expressed in the cytoplasm of hepatocytes. B7/BB-1-positive cells accompanied liver-infiltrating lymphocytes and were detected near HCV core antigen- and HLA class I-positive cells. B7/BB-1 expression was closely correlated with the activity of viral hepatitis. These findings suggest that B7/BB-1 expression by hepatocytes may be induced by HCV infection and may trigger generation and activation of CTL,which may cause damage to HCV-infected HLA class i-expressing hepatocytes. To elucidate the risk factors for liver carcinogenesis and to examine the incidence of hepatocellular carcinoma (HCC) after interferon therapy, 1022 chronic hepatitis C patients treated with interferon were followed by ultrasonography for 13-97 months. The cumulative incidence of HCC in transient responders was almost equal to that in sustained responders, and it was significantly higher in non-responders than in sustained and transient responders. The … More seventh-year cumulative incidence rates of HCC in sustained responders, transient responders and non-responders were estimated to be 4.3%, 4.7% and 26.1%, respectively. Cox regression analysis showed that patients in the high risk gropu of HCC after interferon therapy were those showing no response, who were older and who were male.The hammer-head ribozymes directed against HCV RNA cleaved the target HCV RNA and showed a significant inhibitory effect on viral translation, suggesting that ribozyme-mediated HCV RNA cleavage may serve as a new strategy in the treatment of HCV infection. Human B7-1 transfected HCC 'Is could induce cytolitic activity in vitro compared with B7-1 non-transfected HCC cells, suggesting that human HCC cells with strong expression of B7-1 by ex vivo or in vivo transfection could be used to induce antitumor immunity against human HCC.Tumor growth of B7-1 transfected HCC cells in syngenetic BALB/c nu/nu mouse was as fast as that of wild HCC cells. However, tumor growth of B7-1 transfected HCC cells in syngenetic BALB/c mouse was significantly inhibited compared with that of wild HCC cells, suggesting that antitumor immunity against HCC cells was induced by B7-1 transfected HCC cells in vivo. Thus, B7-1 gene transfer into HCC cells may be one of the candidates for human HCC gene therapy.These findings may lead to clarify the mechanism of liver damage and to improve the efficacy of the treatment for patients with chronic HCV infection. Less