Analysis of the molecular mechanism of hepatocarcinogenesis in patients with chronic viral diseases and its application for genetic diagnosis of hepatocellular carcinoma.

扩展单倍型包括I类B54被证明与肝损伤的进展相关，而扩展单倍型包括II类DRB1^*1302-DQB1^*0604和TAP2^*0103与慢性HCV感染中的低肝炎活性相关。因此，单核苷酸多态性可能与慢性HCV感染患者肝脏疾病的发生和/或进展有关。MAPK/ERK在人肝细胞癌（HCC）中的激活在多步骤肝癌发生中发挥重要作用，特别是主要由MAPK/ERK通过c-fos诱导的cyclin D1上调在HCC的进展中发挥重要作用。HCV感染患者的树突状细胞的刺激电位对同种异体抗原受损，但对回忆抗原没有损害。这种损伤的可能机制是它们在基线时CD86和/或IL-12的低表达，而低的同种异体反应可以通过添加IL-2或IL-12来克服。然而，当来自hcv感染患者的树突细胞遇到召回抗原时，它们被激活以恢复细胞因子产生和刺激T细胞增殖的潜力。b7 -1转染的HCC细胞与IL-12联合免疫可诱导对亲代HCC细胞的保护性和治疗性免疫，这种联合治疗可能有助于抑制HCC的复发。干扰素治疗降低了慢性丙型肝炎患者的HCC发病率，表现为谷丙转氨酶的短暂正常化以及干扰素治疗完成后谷丙转氨酶的持续正常化。此外，生存分析和死亡原因的确定表明，干扰素治疗改善了对这种治疗有反应的慢性丙型肝炎患者的长期生存，可能是通过降低肝脏相关疾病的死亡率。这些发现可能有助于阐明肝损伤和肝细胞癌发展的机制，并改善慢性HCV感染患者的长期临床预后。少

Extended haplotypes including class I B54 is demonstrated to be associated with the progression of liver injury, whereas extended haplotypes including class II DRB1^*1302-DQB1^*0604 and TAP2^*0103 to be associated with low hepatitis activity in chronic HCV infection. Thus, single nucleotide polymorphism may be related to the development and/or progression of liver disease in patients with chronic HCV infection.MAPK/ERK activation in human hepatcellular carcinoma (HCC) is shown to play an important role in multistep hepatocarcinogenesis, especially in the progression of HCC through cyclin D1 up-regulation primarily induced by MAPK/ERK via c-fos.The stimulatory potentials of dendric cells from patients with HCV infection are impaired against alloantigens but not against recall antigens. The possible mechanism for such impairment are their low expression of CD86 and/or IL-12 at the baseline, and low allogenic response could be overcome by the addition of IL-2 or IL-12. However, when dendr … More ic cells from patients with HCV-infection encounter recall antigens, they are activated to restore the potentials for cytokine production and stimulation of T cell proliferation. The combination of immunization of B7-1-transfected HCC cells and IL-12 could induce protective and therapeutic immunity against parental HCC cells, and this combination therapy may be useful for suppressing recurrence of HCC.Interferon therapy lowered the incidence of HCC among ratients with chronic hepatitis C showing transient normalization of ALT as well as sustained normalization of ALT after the completion of interferon therapy. Moreover, survival analyses and determination of cause of death suggest that interferon therapy improves the long-term survival of chronic hepatitis C patients who responded to this therapy, possibly by decreasing mortality from liver-related diseases.These findings may lead to clarify the mechanism of the development of liver damage and hepatocellular carcinoma and to improve the long-term clinical outcome of patients with chronic HCV infection. Less