丙型肝炎病毒感染与2型糖尿病相关性研究进展

doi:10.3969/j.issn.1672-5069.2016.02.038

摘要/Abstract

摘要： 丙型肝炎病毒（HCV）感染与2型糖尿病（T2DM）发生关系密切。HCV影响T2DM的机制主要有干扰胰岛素信号传导、促进肿瘤坏死因子α过度表达、影响脂质代谢和铁代谢、导致胰腺细胞损伤等。T2DM在HCV各种相关并发症的发生中扮演重要角色,T2DM可引起HCV患者肝脏脂肪变性,加重肝纤维化进展,造成抗病毒治疗失败,甚至还能促进肿瘤的发生。

关键词: 丙型肝炎, 2型糖尿病, 胰岛素抵抗, 信号传导通路

Abstract: Hepatitis C virus （HCV） infection is causally associated with diabetes mellitus type Ⅱ（T2DM）. Various mechanisms have been proposed explaining involvement of HCV infection in the process of T2DM occurrence,including the interference of insulin signaling pathway,overexpression of tumor necrosis factor-α,lipid and iron metabolism inbalance,resulting in pancreatic cell damage and so on. T2DM is one of various complications associated with HCV infection. T2DM may result in hepatic steatosis,fibrosis,failure to anti-viral treatment and hepatocellular carcinoma. In this review,we summarize some available information related to HCV infection and T2DM.

Key words: Hepatitis C, Diabetes mellitus type Ⅱ, Insulin resistance, Signaling pathway

李平(综述), 汪茂荣(审校). 丙型肝炎病毒感染与2型糖尿病相关性研究进展[J]. 实用肝脏病杂志, 2016, 19(2): 253-256.

Li Ping, Wang Maorong. Hepatitis C virus infection and diabetes mellitus type Ⅱ occurrence[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(2): 253-256.

参考文献

[1] Peres DP,Cheinquer H,Wolf FH,et al. Prevalence of insulin resistance in chronic hepatitis C genotype 1 and 3 patients. Ann Hepatol,2013,12（6）:871-875.
[2] Mehta SH,Brancati F L,Strathdee S A,et al. Hepatitis C virus infection and incident type 2 diabetes. Hepatology,2003,38（1）:50-56.
[3] Moucari R,Asselah T,Cazals-Hatem D,et al. Insulin resistance in chronic hepatitis C:association with genotypes 1 and 4, serum HCV RNA level,and liver fibrosis. Gastroenterology,2008,134（2）:416-423.
[4] 赵平,王江滨,焦健. 慢性丙型肝炎患者2型糖尿病并发率调查及其基因型特征分析. 中华肝脏病杂志,2006,14（2）:86-88.
[5] 刘孙琴,董明国,门诚虹,等. 慢性丙型肝炎与2型糖尿病关系研究. 中华实用诊断与治疗杂志,2011,25（1）:83-84.
[6] Sporea I,Sirli R,Hogea C,et al. Diabetes mellitus and chronic HCV infection. Rom J Intern Med,2009,47（2）:141-147.
[7] Laloo D,Walke P,Bhimo T,et al. Seroprevalence of hepatitis C infection in type 2 diabetes mellitus. Indian J Endocrinol Metab,2015,19（2）:296-299.
[8] 韦艳妮,梁能秀,苏齐鉴,等. 丙型肝炎病毒感染与2型糖尿病发病关系的研究. 热带医学,2013,13（1）:17-19.
[9] Ruhl C E,Menke A,Cowie C C,et al. Relationship of hepatitis C virus infection with diabetes in the U.S. population. Hepatology,2014,60（4）:1139-1149.
[10] Cusi K. The relationship between hepatitis C virus infection and diabetes:time for a divorce Hepatology,2014,60（4）:1121-1123.
[11] Aytug S,Reich D,Sapiro L E,et al. Impaired IRS-1/PI3-kinase signaling in patients with HCV:a mechanism for increased prevalence of type 2 diabetes. Hepatology,2003,38（6）:1384-1392.
[12] Banerjee S,Saito K,Ait-Goughoulte M,et al. Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance. J Virol,2008,82（6）:2606-2612.
[13] Bose S K,Shrivastava S,Meyer K,et al. Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance. J Virol,2012,86（11）:6315-6322.
[14] Kawaguchi T,Yoshida T,Harada M,et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol,2004,165（5）:1499-1508.
[15] Pazienza V,Clement S,Pugnale P,et al. The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. Hepatology,2007,45（5）:1164-1171.
[16] Pawlak K,Mysliwiec M,Pawlak D. Chronic viral hepatitis and iron affect the plasma levels of LIGHT a new member of the TNF superfamily in uraemic haemodialyzed patients. Cytokine,2007,39（3）:201-206.
[17] Knobler H,Zhornicky T,Sandler A,et al. Tumor necrosis factor-alpha-induced insulin resistance may mediate the hepatitis C virus-diabetes association. Am J Gastroenterol,2003,98（12）:2751-2756.
[18] Shintani Y,Fujie H,Miyoshi H,et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology,2004,126（3）:840-848.
[19] Camma C,Bruno S,Di Marco V,et al. Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C. Hepatology,2006,43（1）:64-71.
[20] Machado M V,Oliveira A G,Cortez-Pinto H. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients. J Gastroenterol Hepatol,2011,26（9）:1361-1367.
[21] Castera L,Hezode C,Roudot-Thoraval F,et al. Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C:indirect evidence of a role of hepatitis C virus genotype 3 in steatosis. Gut,2004,53（3）:420-424.
[22] Perlemuter G,Sabile A,Letteron P,et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J,2002,16（2）:185-194.
[23] Kim K H, Hong S P,Kim K,et al. HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARgamma. Biochem Biophys Res Commun,2007,355（4）:883-888.
[24] Petta S,Camma C,Di Marco V,et al. Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection. Liver Int,2011,31（4）:507-515.
[25] 刘阳珍,肖新强,成镀,等. 丙型肝炎病毒非结构蛋白质5A抑制Hepcidin基因表达并促进肝细胞内铁储留. 中华肝脏病杂志,2011,19（12）:894-897.
[26] Huang J,Jones D,Luo B,et al. Iron overload and diabetes risk: a shift from glucose to fatty acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes,2011,60（1）:80-87.
[27] Neri S,Bruno C M,D'Angelo G,et al. Peripancreatic lymphoadenopathy and extrahepatic immunological manifestations in chronic hepatitis C. Eur J Clin Invest,1996,26（8）:665-667.
[28] Sigal SH,Stanca CM,Kontorinis N,et al. Diabetes mellitus is associated with hepatic encephalopathy in patients with HCV cirrhosis. Am J Gastroenterol,2006,101（7）:1490-1496.
[29] Huang YW,Yang SS,Fu SC,et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis C patients with new-onset diabetes: a nationwide cohort study. Hepatology,2014,60（3）:807-814.
[30] Elkrief L,Chouinard P,Bendersky N,et al. Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C. Hepatology,2014,60（3）:823-831.
[31] Arase Y, Kobayashi M, Suzuki F,et al. Effect of type 2 diabetes on risk for malignancies includes hepatocellular carcinoma in chronic hepatitis C. Hepatology,2013,57（3）:964-973.
[32] Kawaguchi T, Ide T,Taniguchi E,et al. Clearance of HCV improves insulin resistance,beta-cell function,and hepatic expression of insulin receptor substrate 1 and 2. Am J Gastroenterol,2007,102（3）:570-576.
[33] Romero-Gomez M,Fernandez-Rodriguez C M,Andrade R J,et al. Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C. J Hepatol,2008,48（5）:721-727.
[34] Hsu Y C,Lin J T,Ho H J,et al. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology,2014,59（4）:1293-1302.
[35] Zhang X,Harmsen W S,Mettler T A,et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology,2014,60（6）:2008-2016.
[36] Chojkier M,Elkhayat H,Sabry D,et al. Pioglitazone decreases hepatitis C viral load in overweight,treatment naive,genotype 4 infected-patients:a pilot study. PLoS One,2012,7（3）:e31516.
[37] Harrison S A,Hamzeh F M,Han J,et al. Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin. Hepatology,2012,56（2）:464-473.