The mechanism which causes fulminant hepatic failure after immune suppression therapy on HBV carrier patients

乙型肝炎病毒携带者免疫抑制治疗后导致暴发性肝衰竭的机制

• 批准号: 11670480
• 负责人: MARUYAMA Toshiyuki
• 金额: $ 1.92万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670480/
• 关键词: HBV-DNA; fulminant hepatitis; immune suppression therapy; mutation; cytokine; HBV; 劇症肝炎; 免疫抑制剤; HBVキャリアー; 塩基配列; TNFα; IL1; IFNγ

13 HBV carrier patients (group A) who developed fulminant hepatic failure after immune suppression therapy and 11 HBV carrier patients (group B) who did not develop hepatitis after immune suppression therapy were analyzed for liver function test, and cytokine production and virological profile.We analyzed the nucleotide sequence in the whole genome of HBV-DNA from patients to investigate the virological factor. A precore stop codon mutation at nucleotide position 1896 or an A-to-T mutation at nucieotide position 1762 and a G-to-A mutation at nucleotide position 1764 in the core promoter region were frequently present in patients from group A as well as group B.Fulminant HBV infection does not appear to be caused by a specific genomic mutation or an amino acid mutation. To the contrary, the average interleukin 1 levels were higher in group A than that in group B. Similarly, and tumor necrosis factor alfa levels were higher in group A than that in group B.

对13例经免疫抑制治疗后发生暴发性肝功能衰竭的HBV携带者（A组）和11例经免疫抑制治疗后未发生肝炎的HBV携带者（B组）进行肝功能、细胞因子和病毒学检测，并对患者HBV-DNA全基因组核苷酸序列进行分析，探讨其病毒学因素。在A组和B组患者中，核心启动子区核苷酸1896位的前C终止密码子突变或核苷酸1762位的A至T突变和核苷酸1764位的G至A突变频繁出现。暴发性HBV感染似乎不是由特定的基因组突变或氨基酸突变引起的。A组IL-1水平明显高于B组。A组肿瘤坏死因子α水平高于B组。

项目成果

Moriya K., Koike K: "Increase in the concentration of carbon 18 monounsaturated fatty acids in the liver with hepatitis C: analysis in transgenic mice and humans"Biochemical & Biophysical Research Communications. 281. 1207-12 (2001)

Moriya K.、Koike K：“丙型肝炎导致肝脏中碳 18 单不饱和脂肪酸浓度增加：转基因小鼠和人类的分析”生物化学

Maruyama T.: "Emergence of the Precore Mutant Late in Chronic Hepatitis B Infection Correlates With the Severity of Liver Injury and Mutations in the Core Region"American Journal of Gastroenterology. 95. 2894-2904 (2000)

Maruyama T.：“慢性乙型肝炎感染晚期预核心突变体的出现与核心区域肝损伤和突变的严重程度相关”《美国胃肠病学杂志》。

Koike K: "Transgenic mouse model of viral hepatitis : Insight into viral hepatocarcinogenesis"Viral Hepatitis Rev.. 5. 177-203 (1999)

Koike K：“病毒性肝炎的转基因小鼠模型：病毒性肝癌发生的见解”Viral Hepatitis Rev.. 5. 177-203 (1999)

Aoki K. et al.: "The DNA binding activity of translin is mediated by a basic region in the ring-shaped structure conserved in evolution"FEBS Letters. 443. 363-366 (1999)

Aoki K. 等人：“易位蛋白的 DNA 结合活性是由进化中保守的环形结构中的基本区域介导的”FEBS Letters。

Aoki K.: "The DNA binding activity of Translin is mediated by a basic region in the ring-shaped structure conserved in evolution"FEBS Letters. 443. 363-366 (1999)

Aoki K.：“Translin 的 DNA 结合活性是由进化中保守的环形结构中的基本区域介导的”FEBS Letters。