肝纤维化检验诊断进展与评价

肝脏损伤能刺激肝细胞再生和/或肝纤维化。肝纤维化是造成肝功能异常和影响慢性肝病预后的重要因素之一,亦是慢性肝病发展到肝硬化必经阶段,现认为肝纤维化尚有逆转至正常可能,而肝硬化则否。世界著名已故肝病专家Hans Popper认为谁能阻止或减慢肝纤维化的发生,将会治愈大多数慢性     

肝纤维化血清学无创检测研究进展

肝纤维化指肝脏细胞外基质弥漫性的过度沉积,是机体对于肝实质损伤的一种修复反应及许多慢性肝病共同的病理过程,也是各种慢性肝病向肝硬化发展的重要步骤.迄今为止,临床尚缺乏特异性有效逆转或阻止肝纤维化进展的药物,尽早对肝纤维化进行诊断具有重要意义.目前肝纤维化的诊断主要靠组织病理学、血清学标志物及影像学手段.肝活检被认为是肝...     

水飞蓟素在抗肝纤维化中的应用

肝纤维化是各种病因引起慢性肝损伤,激活肝星状细胞(HSC),导致细胞外基质(ECM)合成大于降解进而在肝脏异常沉积的结果,进一步发展,则引起肝小叶结构改建,假小叶形成,称为肝硬化.肝纤维化是慢性肝病重要的病理特征,也是肝硬化发生的前奏和必经中间环节.近年来有关肝纤维化的研究取得了长足进展,水飞蓟素(silymarin)在世界各国治疗肝病已有数千年的历史,其在抗肝纤维化中的作用值得人们关注.     

枯否细胞在肝纤维化中的作用

枯否细胞(Kupffer cells,KC)是肝脏内一种重要的非实质细胞,其在发挥防御作用的同时,可释放多种化学介质介导肝脏损伤,在诸多肝脏病理性改变中起重要作用.肝纤维化(hepatic fibrosis,HF)是诸多慢性肝病共同的病理过程,也是各种慢性肝病向肝硬化转归的中转站.KC分泌的细胞因子作为重要的影响因素,参与HF的发生与发展.因此,深入研究KC在HF发生与发展中的作用和机制,并研究与KC相关的抗纤维化治疗策略及方法,对于临床工作中防治肝脏损伤,提高患者生存率具有实际意义.     

肝脏自然杀伤细胞在慢性肝病中的作用

肝脏自然杀伤细胞（NK）是一种与外周血NK细胞不同的肝脏免疫细胞。近年来研究表明肝脏NK细胞在各种慢性肝脏疾病中起重要作用。包括对抑制病毒感染和肿瘤细胞生长,对抗肝纤维化均有益处,但同时其又刺激肝损伤和抑制肝再生（肝细胞增殖）。本文就肝脏NK细胞的特征、功能以及在各种常见慢性肝病中作用进展作一综述。     

以TGF-β为靶点的抗肝纤维化治疗

肝脏纤维化是慢性肝病最重要的病理特征，转化生长因子-β（TGF-β）通过对肝星状细胞／肌成纤维细胞及与其他细胞因子之间的相互作用，对肝纤维化的形成和发展起着至关重要的作用。对TGF-β认识的逐步加深，使得肝脏纤维化的治疗又有了新的突破。本文就近年来TGF-β的研究进展以及以其为靶点治疗肝纤维化的现状作一综述。     

肝纤维化研究进展

肝纤维化是各种损伤因子累及肝脏后的一种病理状态。几乎任何能造成肝脏损害的因素均可致肝脏发生纤维化,如慢性乙型肝炎、慢性丙型肝炎、脂肪性肝炎(包括酒精性或非酒精性)、自身免疫性肝病、血吸虫肝病、药物性肝病和一些先天代谢性疾病等均可引起肝纤维化。在此病理进程中,正常功能的肝细胞数量减少,肝小叶结构改变,血液循环紊乱,致肝脏功能逐渐丧失,最终发展为肝硬化。随着医学科学的     

肝纤维化的超声诊断

一、慢性肝病肝纤维化超声诊断指标 有直接诊断指标、间接诊断指标. 1.直接诊断指标:通过超声直接观察肝脏的实质回声形态、肝包膜、肝边缘角、肝静脉壁的改变,直接判断肝纤维化的程度[1].     

抗肝纤维化药物的现状和展望

肝纤维化是肝脏对慢性损伤的一种修复反应,是慢性肝病共有的病理改变。肝纤维化的常见病因有病毒性肝炎、慢性酒精中毒、脂肪肝、血吸虫、肝脏淤血、淤胆、自身免疫、遗传和代谢性疾病、化学毒物或药物等,其特征是以胶原为主的细胞外基质（ECM）在肝内过多沉积。肝纤维化属可逆病变,其治疗主要是在有效去除病因的基础上,针对不同环节,采取相应措施,     

肝纤维化治疗策略探讨

肝纤维化是肝脏对慢性损伤的修复反应，是慢性肝病共有的病理改变，其特征是以胶原为主的细胞外基质(extracellular matrix，ECM)在肝内过多沉积。肝纤维化为一动态过程，属可逆性病变，阻断、抑制或逆转肝纤维化是治疗慢性肝病的重要目标。     

Adipocytokines and liver disease

Adipose tissue is a massive source of bioactive substances known as adipocytokines, including tumor necrosis factor (TNF)-α, resistin, leptin, and adiponectin. Recent advances in medical research view obesity as a chronic low-grade inflammatory state. Hypertrophied adipocytes in obesity release chemokines that induce macrophage accumulation in adipose tissue. Accumulated macrophages in obese adipose tissue produce proinflammatory cytokines and nitric oxide, and these inflammatory changes induce adipocytokine dysregulation. The latter is characterized by a decrease in insulinsensitizing and anti-inflammatory adipocytokines, and an increase in proinflammatory adipocytokines. Adipocytokine dysregulation induces obesity-related metabolic disorders, the so-called metabolic syndrome. Metabolic syndrome is a cluster of metabolic abnormalities, including diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic steatohepatitis (NASH). Recent studies have revealed that obesity is an independent risk factor for chronic liver diseases, such as NASH, alcoholic liver disease, chronic hepatitis C, and hepatocellular carcinoma. A common mechanism underlying these hepatic clinical states is thought to be adipocytokine dysregulation. In this review, we discuss the association of adipocytokines, especially leptin, adiponectin, TNF-α, and resistin, with liver diseases.     

Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines

Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions.     

脂联素与慢性肝病研究进展

脂联素(adiponectin)是脂肪细胞因子家族的重要成员之一,具有增强胰岛素敏感性、抗炎、抗动脉粥样硬化及负性调节免疫功能等多种作用。随着对脂联素研究的深入,发现其与慢性肝病的发生密切相关。文章就脂联素的来源、结构、生物学功能及其在慢性肝病中的表达情况和其在慢性肝病治疗中的潜在效应作一综述。     

Decreased plasma adiponectin concentrations are closely related to steatosis in hepatitis C virus-infected patients

OBJECTIVES: The mechanisms underlying steatosis during hepatitis C virus (HCV) infection are complex and multifactorial. Obesity is a well-recognized risk factor for the development of steatosis in chronic hepatitis C infection. The aim of our study was to investigate the role of adipocytokines in HCV-related steatosis. Therefore, we hypothesized that the endocrine function of adipose tissue could be, in part, responsible for HCV-related steatosis. Seventy-one consecutive untreated chronic hepatitis C patients were studied to assess the effects of adipocytokines, body mass index (BMI), age, and HCV genotype on steatosis. We used ELISA to determine serum adiponectin, leptin, and soluble TNF receptors I and II concentrations. RESULTS: Steatosis was observed in 42 (59.1%) patients. BMI was significantly associated with leptin (r = 0.64; P = 0.0001) and was border significantly associated with adiponectin concentrations (r = -0.22; P = 0.06). In univariate analyses, age, HCV genotype 3, BMI, increased leptin level, increased insulin level, and decreased adiponectin concentration were associated with steatosis. In multivariate analysis, steatosis was significantly associated with low adiponectin concentration, age, HCV genotype 3, and aspartate aminotransferase (ASAT) level, whereas steatosis was not associated with leptin, insulin, and BMI. CONCLUSION: In chronic HCV patients, hypoadiponectinemia is significantly associated with the development of liver steatosis. The fact that the plasma levels of adiponectin inversely correlate with steatosis in HCV-infected subjects suggests that hypoadiponectinemia may contribute to hepatic steatosis progression and liver injury in this population. One practical implication is that therapy to increase circulating adiponectin concentration, such as overweight reduction or thiazolidinediones, provides the potential to improve steatosis in chronic hepatitis C infection.     

Mechanisms of disease: adipocytokines and visceral adipose tissue--emerging role in nonalcoholic fatty liver disease

There is increasing evidence that visceral adipose tissue is a causative risk factor for fatty liver and nonalcoholic steatohepatitis. Adipose tissue-derived secretory proteins are collectively named adipocytokines. Obesity and mainly visceral fat accumulation impair adipocyte function and adipocytokine secretion and the altered release of these proteins contributes to hypertension, impaired fibrinolysis and insulin resistance. This review summarizes recent findings on the role of the adipocytokines adiponectin, leptin and resistin in the context of hepatic insulin resistance, fatty liver and liver fibrosis. Elevated levels of resistin antagonize hepatic insulin action and raise plasma glucose levels. Leptin exerts insulin-sensitizing effects, but obesity has been linked to leptin resistance and low levels of circulating leptin receptor, indicating that high levels of leptin cannot mediate its beneficial effects. Adiponectin improves insulin sensitivity; however, low circulating adiponectin is found in the obese state. Adiponectin is an anti-inflammatory protein, whereas leptin augments inflammation and fibrogenesis. Disturbed adipocytokine secretion might, therefore, promote hepatic steatosis and the development of nonalcoholic steatohepatitis. The beneficial effects of the therapeutic approaches so far tested in the treatment of fatty liver disease and fibrosis might be due to the modulation of these adipocytokines.     

Association of coffee consumption with serum adiponectin,leptin, inflammation and metabolic markers in Japanese workers: a cross-sectional study

Background:

Mechanisms underlying coffee''s beneficial actions against cardiovascular disease and glucose metabolism are not well understood. Little information is available regarding association between coffee consumption and adipocytokines.

Objective:

We investigated potential associations between coffee consumption and adiponectin, leptin, markers for subclinical inflammation, glucose metabolism, lipids and liver enzymes. We then investigated whether adipocytokines played a role in the association between coffee consumption and these markers.

Design and subjects:

This is a cross-sectional study comprising 2554 male and 763 female Japanese workers. Potential relations between coffee consumption and adipocytokines or other markers were evaluated using a multiple linear regression model adjusted for confounding factors. We evaluated whether adiponectin and leptin partly explain the associations between coffee consumption and each marker by multiple mediation analysis.

Results:

Coffee consumption showed significant positive associations with adiponectin and total and low-density lipoprotein cholesterol, and inverse associations with leptin, high sensitivity C-reactive protein (hs-CRP), triglycerides and liver enzymes (all P<0.05). An adjustment for adiponectin and leptin significantly attenuated the associations between coffee consumption and hs-CRP or triglycerides, but not for liver enzymes. No associations were observed between coffee consumption and glucose metabolism-related markers.

Conclusion:

Coffee consumption was associated with high adiponectin and low leptin levels. We speculated that adipocytokines mainly explain the associations of coffee consumption with lipids and hs-CRP. Factors other than adipocytokines may explain the association between coffee consumption and liver function.     

Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

The role of tumor necrosis factor alpha, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCV-infected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63, P = 0.01), TNFalpha (1.28 versus 0.60 pg/ml, P < 0.001) and IL6 (2.42 versus 1.15 pg/ml, P = 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. By multiple linear regression, independent predictors of HOMA-IR included the body mass index, and the serum levels of leptin (positive correlation) and adiponectin (negative correlation), but not that of TNFalpha and IL6. Only TNFalpha levels were correlated with the extent of histological injury (portal/periportal inflammation, P = 0.02). CONCLUSION: Whereas leptin and adiponectin contribute to IR, none of the adipocytokines accounted for the elevated IR in HCV-infected subjects. The adipocytokines were not associated with histological features of chronic HCV infection except for TNFalpha which correlated with portal/periportal inflammation. HCV-associated IR is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity.     

Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines

BACKGROUND: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue. METHODS: Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding. RESULTS: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue. CONCLUSIONS: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.     

A role for novel adipose tissue‐secreted factors in obesity‐related carcinogenesis

Obesity, a pandemic disease, is caused by an excessive accumulation of fat that can have detrimental effects on health. Adipose tissue plays a very important endocrine role, secreting different molecules that affect body physiology. In obesity, this function is altered, leading to a dysfunctional production of several factors, known as adipocytokines. This process has been linked to various comorbidities associated with obesity, such as carcinogenesis. In fact, several classical adipocytokines with increased levels in obesity have been demonstrated to exert a pro‐carcinogenic role, including leptin, TNF‐α, IL‐6 and resistin, whereas others like adiponectin, with decreased levels in obesity, might have an anti‐carcinogenic function. In this expanding field, new proteomic techniques and approaches have allowed the identification of novel adipocytokines, a number of which exhibit an altered production in obesity and type 2 diabetes and thus are related to adiposity. Many of these novel adipocytokines have also been identified in various tumour types, such as that of the breast, liver or endometrium, thereby increasing the list of potential contributors to carcinogenesis. This review is focused on the regulation of these novel adipocytokines by obesity, including apelin, endotrophin, FABP4, lipocalin 2, omentin‐1, visfatin, chemerin, ANGPTL2 or osteopontin, emphasizing its involvement in tumorigenesis.