Treatment for chronic hepatitis C with metallothionein induction by IFN

1.研究了IL-6、地塞米松（Dex）和锌对大鼠金属硫蛋白（MT）合成的相互影响。MT在肝脏中的合成由11-6或Dex诱导，并且以相加的方式由LL-6和Dex的组合诱导。由[L-6]和Dex与Zn的组合诱导的肝MT的增加大于由（1 L-6 +Zn）和由（Dex + Zn）诱导的增加的总和，表明协同增加。结果表明，IL-6联合Dex诱导MT的最大增加依赖于足够的肝锌含量。2.我们研究了IFN对16例慢性丙型肝炎患者肝组织MT诱导和HCV清除的影响。非活动性肝炎患者肝脏MT浓度高于活动性肝炎患者。16例患者中7例经IFN治疗后肝组织中HCV被根除，肝MT染色较HCV阳性者明显。此外，IFN联合锌治疗组肝组织MT-mRNA的诱导表达较单独IFN治疗组增加.目的：探讨干扰素联合锌治疗Ib基因型丙型肝炎的疗效。15例患者接受IFN和160 mg Polaprezinc治疗24周。对照组61例，单用肠内营养治疗。在6个月随访期结束时，血清ALT水平正常化（联合组67%，对照组42%）和HCVRNA根除结果表明，肝内MT的诱导对肝脏炎症反应的抑制作用是必要的，联合应用锌可提高干扰素治疗丙型肝炎的疗效。

1. We investigated the reciprocal effects of IL-6, dexamethasone (Dex) and Zn on metallothionein (MT) synthesis in rats. MT synthesis in the liver was induced by 11-6 or Dex, and in an additive manner by a combination of LL-6 and Dex. The increase in liver MT induced by the combination of [L-6 and Dex with Zn was greater than the sum of the increases induced by (1L-6 +Zn) and by (Dex + Zn), suggesting a synergistic increase. The data indicate that the maximal increase in the induction of MT by a combination of IL-6 and Dex depends on an adequate liver Zn content.2.We studied the effect of IFN on MT induction and HCV clearance in human liver tissue obtained from 16 patients with chronic hepatitis C.Liver histology of 11 patients was improved by IFN therapy from active type to inactive type. Hepatic MT concentration was increased in patients with inactive hepatitis more than in those with active hepatitis. Seven out of 16 patients eradicated HCV from liver tissue by IFN therapy, in whom hepatic MT stains were marked compared to those of HCV positive ones. In addition, MT-mRNA induction in liver was increased in hepatitis C patients treated with IFN and zinc compared with those treated with IFN alone.3. A pilot study was tried on the effect of combined therapy with IFN and zinc for hepatitis C patients with genotype lb. Fifteen patients were treated by IFN and 160 mg of polaprezinc for 24 weeks. Sixty one patients treated with IEN alone as same schedule served control. At the end of 6 months follow up period, normalization of serum ALT levels(combined group 67%, control 42%) and eradication of HCVRNA(combined group 53%, control 16%) were higher in the patients treated with IEN and zinc than in those treated with IFN alone.These results suggest MT induction is needed to calm of hepatic inflammation, and therapeutic effect of IFN for hepatitis C may improved in combination with zinc.