肝炎病毒感染与胰岛素抵抗

肝炎病毒慢性持续感染主要是由乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)所致, 除了引起肝脏损害外, 还与一些肝外组织的损害密切相关. 近年来, 研究资料显示慢性HCV和HBV感染与糖尿病和脂肪肝等代谢性疾病的发病密切相关, 而胰岛素抵抗(IR)可能是其发病机制的中心环节. IR也是肝纤维化进展的相关因素, 并影响慢性肝炎病毒感染时抗病毒治疗的疗效. 此外, 糖尿病还可能增加肝炎病毒致癌的作用, 应该引起肝病医师的高度重视. 本文就近年来对HCV和HBV感染中IR发生机制方面的研究, IR在HCV和HBV感染相关的糖尿病和脂肪肝中的作用和影响及其对临床的指导意义作一述评.     

慢性丙型肝炎与糖尿病的相关性

慢性丙型肝炎(CHC)是由丙型肝炎病毒(HCV)感染引起的一种慢性感染性肝脏疾病[1].HCV是一种RNA病毒,与乙型肝炎病毒(HBV)这种DNA病毒的致病机制不同.目前已经积累的临床与研究资料表明,慢性HCV感染不仅引起CHC、肝硬化、肝细胞癌,而且还引起一系列的全身性的代谢疾病,我们曾经提出HCV感染引起的多代谢综合征(metabolicdisturbance syndrome))的概念[2].近年来的研究资料表明,HCV感染可以引起2型糖尿病(NIDDM)的发生[3].     

慢性丙型肝炎与2型糖尿病关系的研究进展

肝脏在血糖代谢中起重要作用，有研究表明肝硬化与糖尿病有密切相关系，丙型肝炎是导致肝硬化的主要原因之一，丙型肝炎病毒（HCV）感染可能导致糖尿病特别是2型糖尿病的发生。本文综述可能与其相关的影响因素包括年龄，肝硬化、HCV基因型及遗传因素等的研究现状，发病机制可能与自身免疫，HCV复制，铁代谢，肝脂肪变，胰岛素抵抗等有关。     

丙型肝炎免疫学发病机制研究进展

从丙型肝炎病毒抗原与免疫细胞、免疫介导的肝脏损害、免疫复合物及其作用和细胞因子与免疫调节等方面介绍了丙型肝炎免疫学发病机制研究的新进展。     

丙型肝炎病毒感染与脂类代谢的相关性

临床上发现慢性丙型肝炎肝脏病理特征十分突出的一点就是脂肪变性。慢性实验性感染丙型肝炎病毒 (ＨＣＶ)的黑猩猩肝脏脂肪变也是常见的一种病理改变。ＨＣＶ核心蛋白编码基因的转基因小鼠 ,其肝脏也有明显的脂肪变性改变 ,所以目前关于ＨＣＶ感染与机体脂肪代谢紊乱的问题引起了人们的关注。现有的研究表明 ,ＨＣＶ感染与肝脏的脂类代谢有着十分密切的关系。一、血清ＨＣＶ与血脂成分的结合关于ＨＣＶ与脂类代谢的相互关系 ,首先注意到的是ＨＣＶ病毒颗粒与血清中不同的脂蛋白成分结合的能力。ＨＣＶ病毒颗粒与血清中不同的脂蛋白成分结合 …     

丙型肝炎与肝脏脂肪变的相关性

丙型肝炎病毒(HCV)感染,除了引起急性丙型肝炎(AHC)、慢性丙型肝炎(CHC),与肝纤维化(LF)、肝细胞癌(HCC)的发生发展密切相关之外,与肝脏脂肪变、冷球蛋白血症、B细胞淋巴瘤(BCL)等也有密切的关系。说明HCV感染的致病机理与其他类型的肝炎病毒截然不同。关于HCV感染与肝脏脂肪变之间的关系,近年来积累了丰富的临床     

铁对丙型肝炎病毒感染及治疗的影响

铁是人体所必须的微量元素,主要存在于血液中,其次是肝脏.在血液中其通过转铁蛋白转运,以铁蛋白(Fn)形式贮存于肝脏.血清中仅少量铁蛋白.铁还是体内多种酶和酶系的辅基,参与氧化还原反应,影响宿主免疫性和非免疫性防御机制,特别是,铁和铁结合蛋白在淋巴细胞和自然杀伤细胞(NK)的增殖及其功能以及单核细胞的吞噬活性中起着重要作用.近几年研究显示铁代谢与丙型肝炎病毒(HCV)感染密切相关,可作为慢性丙型肝炎(CHC)干扰素(IFN)治疗的预测因素之一.     

抗病毒药物治疗丙型肝炎现状

丙型肝炎是由丙型肝炎病毒(HCV)通过血液途径感染人体引起肝细胞损害的疾病,感染时间越短,肝脏病理损害越轻,治疗效果越好;若在急性期来进行合理治疗,可有90％以上病例发生慢性     

丙型肝炎肝硬化中西医治疗近况

丙型病毒性肝炎(简称丙型肝炎)是由丙型肝炎病毒(HCV)引起的肝脏炎症性疾病.HCV感染呈全球性分布,主要通过血液传播.据世界卫生组织统计,全球HCV感染率约为3%,估计有1.7亿人感染HCV,每年新发丙型肝炎病例约3.5万.     

肝脏疾病的病理学现状

一、丙型肝炎电镜检查感染丙型肝炎病毒 (HCV )的人类和黑猩猩的肝脏发现平行排列的短管结构 (病毒外壳物质 )和直径为 5 0～ 6 0nm的病毒样颗粒。感染HCV的人 ,其淋巴细胞内显示有这种短管的聚集。慢性丙型肝炎肝活检标本常常显示肝脂肪变性 ,且基因表型 3a和体重指数 (BMI)与脂肪变性密切相关。HCV核心蛋白通过导入氧化趋势和活化氧参与脂肪变性。这样依次产生线粒体渗透性改变、细胞色素C释放 ,最终细胞发生凋亡。与转基因小鼠情况相似 ,载脂蛋白正常转运脂质的作用受到HCV蛋白的抑制 ,其中HCV核心蛋白影响载脂蛋白A2 ,非结构抗原 5A(NS5A)则作用于载脂蛋白A1。另有一篇文章进一步讨论了HCV相关脂肪变性的可能机制及HCV核心蛋白与肝细胞肝癌的关系。基因片段分析显示HCV导致的肝硬化与某些基因表达上调有关。对血清转氨酶水平正常的HCV携带者随访 6个月以上 ,约有 2 0 %的携带者出现血清转氨酶升高。流行病学调查显示 ,HCV感染与B淋巴细胞异常增生有关 ,并发现 7例绒毛淋巴细胞型脾淋巴瘤 (脾边缘区淋巴瘤 )患者经α2b干扰素治疗病情彻底缓解 ,其HCVRNA检测为阴性。丙型肝炎患者...     

Mitochondrial reactive oxygen species as a mystery voice in hepatitis C

There are several lines of evidence suggesting that oxidative stress is present in hepatitis C to a greater degree than in other inflammatory liver diseases and is closely related to disease progression. The main production site of reactive oxygen species (ROS) is assumed to be mitochondria, which concept is supported by evidence that hepatitis C virus (HCV) core protein is directly associated with them. The detoxification of ROS also is an important function of the cellular redox homeostasis system. These results draw our attention to how HCV‐induced mitochondrial ROS production is beyond redox regulation and affects the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis C. On the other hand, HCV‐related chronic liver diseases are characterized by metabolic alterations such as insulin resistance, hepatic steatosis and/or iron accumulation in the liver. These metabolic disorders also are relevant to the development of HCC in HCV‐related chronic liver diseases. Here, we review the mechanisms by which HCV increases mitochondrial ROS production and offer new insights as to how mitochondrial ROS are linked to metabolic disorders such as insulin resistance, hepatic steatosis and hepatic iron accumulation that are observed in HCV‐related chronic liver diseases.     

Adiponectin serum level in chronic hepatitis C infection and therapeutic profile

Hepatic steatosis is commonly seen in the patients with chronic hepatitis C virus(HCV) infection. HCV is closely associated with lipid metabolism,and viral steatosis is more common in genotype 3 infection owing to a direct cytopathic effect of HCV core protein. In non-genotype3 infection,hepatic steatosis is considered largely to be the result of the alterations in host metabolism; metabolic steatosis is primarily linked with HCV genotype 1. A d i p o s e t i s s u e s e c r e t e s d i f f e r e n t h o r m o n e s involved in glucose and lipid metabolisms. It has been demonstrated that adipocytokines are involved in the pathogenesis of non-alcoholic fatty liver disease,as the decreased plasma adiponectin levels,a soluble matrix protein expressed by adipoctyes and hepatocyte,are associated with liver steatosis. Various studies have shown that steatosis is strongly correlated negatively with adiponectin in the patients with HCV infection. The role of adiponectin in hepatitis C virus induced steatosis is still not completely understood,but the relationship between adiponectin low levels and liver steatosis is probably due to the ability of adiponectin to protect hepatocytes from triglyceride accumulation by increasing β-oxidation of free fatty acid and thus decreasing de novo free fatty acid production.     

Hepatitis C as a metabolic disease: Implication for the pathogenesis of NASH.

In addition to the link with development of hepatocellular carcinoma (HCC), hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations such as essential mixed cryoglobulinemia, porphyria cutanea tarda or Sj?gren's syndrome. A role of hepatic steatosis in the pathogenesis of chronic hepatitis C has also been known, implying hepatitis C as a metabolic disease. In addition, recent epidemiological studies have suggested a linkage between type 2 diabetes and chronic HCV infection. However, the presence of additional factors in patients, such as obesity, aging or cirrhosis, prevents the establishment of a definite relationship between HCV infection and these two conditions, lipid metabolism disturbance and diabetes. In addition to the data indicating the presence of dyslipidemia and diabetes or insulin resistance in our cohort of chronic hepatitis C patients, we found a series of evidence showing the association between the conditions and HCV infection in mouse models that are transgenic for the HCV genes. In patients with chronic hepatitis C, a significant decrease in the serum levels of total cholesterol and apolipoproteins C2 and C3 was observed compared to those with chronic hepatitis B that were comparable in liver function. In an animal model, C18:1 mono-unsaturated fatty acids were significantly increased in the liver from HCV core gene transgenic mice, which was similarly observed in the liver from human hepatitis C patients. Thus, a disturbance in lipid metabolism was observed in both humans and an HCV mouse model, supporting that it is a specific event in HCV infection. A significant increase in the value of an indicator for homeostasis model assessment of insulin resistance (HOMA-IR), was observed in patients with chronic hepatitis C, even at the very early stage of chronic hepatitis. In the animal model, a marked insulin resistance was exhibited from a very young age in HCV core gene transgenic mice. Insulin resistance observed in the core gene transgenic mice was chiefly due to the shortage of insulin action on the suppression of glucose production in the liver. Thus, the ability of insulin to lower the plasma glucose level in the HCV transgenic mice was impaired, as observed in chronic hepatitis C patients. These results provide a direct experimental evidence for the contribution of HCV in the development of insulin resistance in human HCV infection, which finally leads to the development of type 2 diabetes. Insulin resistance may be a critical factor in the pathogenesis of chronic hepatitis C as recently suggested in non-alcoholic steatohepatitis (NASH), along with impairment in lipid metabolism. Our results would provide a clue for further understanding of pathobiology of HCV infection, and may provide an implication for the pathogenesis of NASH.     

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications. METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically. RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13±3.94), (5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.     

Metabolic complications of hepatitis C virus infection

Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.     

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

目的通过调查慢性丙型肝炎患者2型糖尿病并发率及其与所感染丙型肝炎病毒（HCV）基因型的关系。进一步探讨糖尿病是否为丙型肝炎的肝外表现之一。方法采用荧光定量聚合酶链反应和聚合酶链反应一微板核酸杂交酶联免疫技术对308例慢性丙型肝炎、305例慢性乙型肝炎患者进行乙型肝炎病毒、HCV定性．定量检测和HCV基因型分析并比较其与对照人群糖尿病并发率的差异。结果慢性丙型肝炎患者糖尿病并发率为32．79％，明显高于慢性乙型肝炎（9．84％）及对照组（8．39％）。合并糖尿病的慢性丙型肝炎患者血清丙氨酸氨基转移酶及总胆红素水平显著高于未合并糖尿病者，且以1b型HCV的感染率为最高，占40．59％，与未合并糖尿病者相比差异有统计学意义。结论慢性丙型肝炎患者糖尿病并发率高，以1b型多见，且病情相对较重。     

Metabolic aspects of hepatitis C virus

Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.     

慢性肝病患者HCV与HBV重叠感染与预后

目的探讨ＨＣＶ与ＨＢＶ重叠感染对慢性肝病过程、预后及对乙型肝炎病毒复制的影响。方法应用第二代抗＿ＨＣＶＥＬＩＳＡ及ＲＴ＿ＰＣＲ法测定１８７例ＨＢｓＡｇ阳性慢性肝病患者抗＿ＨＣＶ及ＨＣＶ＿ＲＮＡ，并对ＨＣＶ与ＨＢＶ重叠感染者的肝损害，ＨＣＶ，ＨＢＶ间的相互作用及预后进行分析。结果抗＿ＨＣＶ，ＨＣＶ＿ＲＮＡ的阳性率在慢性肝炎（轻度）１３．３％，慢性肝炎（中～重度）１６．１％，肝硬变２２．７％，慢性重型肝炎６３．６％，肝细胞癌１３．３％。平均阳性率１８．２％，慢性重型肝炎抗＿ＨＣＶ，ＨＣＶ＿ＲＮＡ的检出率最高，明显高于肝脏损害的其他肝病（Ｐ＜０．０５），近半数以上ＨＣＶ慢性感染已与ＨＢＶ重叠感染。结论ＨＣＶ与ＨＢＶ重叠感染的慢性肝病患者预后较差。但并未发现ＨＣＶ对ＨＢＶ复制具有阻遏作用。