Insulin resistance and hepatitis C

查看全文 作　　者：Manuel Romero-[1]Gómez

机构地区：[1]Unit for the Clinical Management of Digestive Diseases. Hospital Universitario de Valme. Ctra de Cádiz s/n 41014, Sevilla, Spain

出　　处：《World Journal of Gastroenterology》索引2006年第12卷第44期,共6页

基　　金：Supported by a grant of PAI-CTS-532 from Junta de Andalucía, Andalucía, Spain 摘　　要：Insulin resistance is the major feature of the meta- bolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resist- ance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resist- ance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: “viral” and “metabolic” insulin resistance. In- sulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARγ recep- tors. Lastly, insulin resistance has been found as a com- mon denominator in patients difficult-to-treat like cir- rhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abol- ished. In summary, hepatitis C promotes insulin resist- ance and insulin resistance induces interferon resistance, steatosis and fibrosis progression. 关键词：丙型肝炎纤维化胰岛素乃药性持续反应抗病毒药物

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Insulin resistance and hepatitis C

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