leptin and Liver-Cirrhosis--Biliary

Obesity, a characteristic of metabolic syndrome, is also associated with chronic inflammation and the development of autoimmune diseases. However, the relationship between obesity and autoimmune diseases remains to be investigated in depth. Here, we compared hepatic gene expression profiles among high-fat diet (HFD) mice using the primary biliary cholangitis (PBC) mouse model based on the chronic expression of interferon gamma (IFNγ) (ARE-Del

Topics: Animals; Antigen Presentation; Diet, High-Fat; Energy Metabolism; Interferon-gamma; Leptin; Liver; Liver Cirrhosis, Biliary; Luteolin; Mice; Obesity; Signal Transduction; Th1 Cells

Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease.. Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed.. All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p<0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers.. No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.

Topics: Adjuvants, Immunologic; Aged; Algorithms; Biomarkers; Carcinoma, Hepatocellular; Case-Control Studies; Collagen Type IV; Diagnosis, Differential; Early Diagnosis; Female; Hepatitis C, Chronic; Humans; Hyaluronic Acid; Laminin; Leptin; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Neoplasms; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity

The relationship between metabolic abnormalities of trace elements and insulin resistance has been established. Recent studies have revealed that insulin resistance is associated with autoimmune responses. The purpose of this study was to examine the correlation between zinc or copper metabolism and insulin resistance in patients with primary biliary cirrhosis (PBC). Sixteen patients with PBC were divided into two groups: early and advanced stage disease. The overall value of the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with advanced stage PBC was significantly higher than that in patients with early stage PBC, although the mean value in advanced stage PBC was significantly lower than that in hepatitis C virus (HCV)-related liver cirrhosis. There was an inverse correlation between serum zinc concentrations and HOMA-IR values in patients with PBC, while we found no correlation between serum copper levels and HOMA-IR values. HOMA-IR values were inversely associated with peripheral platelet counts, indicating the relationship between insulin resistance and hepatic fibrosis. These results suggest that zinc deficiency plays important roles of insulin resistance and subsequent hepatic fibrosis in patients with PBC, although insulin resistance in advanced stage PBC was significantly milder than that in HCV-related liver cirrhosis.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Copper; Deuteroporphyrins; Disease Progression; Female; Hepatitis C, Chronic; Homeostasis; Humans; Imines; Insulin Resistance; Japan; Leptin; Liver; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Mitochondria, Liver; Platelet Count; Zinc

The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC).. Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck.. Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease.. We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC.

Topics: Absorptiometry, Photon; Aged; Bone Density; Collagen Type I; Female; Femur Neck; Humans; Leptin; Liver Cirrhosis, Biliary; Lumbar Vertebrae; Middle Aged; Osteocalcin; Osteoporosis; Receptors, Cell Surface; Receptors, Leptin

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology resulting in the progressive destruction of the intrahepatic bile ducts and leading to chronic cholestasis and ultimately liver cirrhosis and failure. The immune response in PBC seems to be mediated by autoantibodies as well as autoreactive T lymphocytes directed against mitochondrial antigens in biliary epithelial cells, primarily PDC-E2. Experimental evidence suggests a role of the hormone/cytokine leptin in autoimmune diseases. Leptin is an adipocyte-derived molecule that acts as a hormone influencing food intake and energy metabolism as well as a cytokine with pro-inflammatory, immune-regulatory functions. To study serum leptin in PBC and its association with disease severity, we evaluated serum levels in 37 patients with PBC (27 with no signs of fibrosis or cirrhosis at histologic examination) and 37 age- and sex-matched healthy controls using a validated ELISA method. We found that patients with PBC had significantly lower leptin serum levels compared with healthy controls (13.6 +/- 13.8 vs. 17.6 +/- 11.6; P < 0.05). No correlation between disease severity and serum leptin levels was found. This study has demonstrated that leptin levels are decreased in the serum of patients with PBC but do not seem to be associated with disease severity. Data do not seem to indicate a direct role of leptin in the perpetuation of the autoimmune response in PBC. However, further studies are warranted to further characterize the functions of leptin during the natural history of autoimmunity.

Topics: Adult; Aged; Aged, 80 and over; Autoimmunity; Cross-Sectional Studies; Female; Humans; Leptin; Liver Cirrhosis, Biliary; Middle Aged

a) To analyze plasma leptin levels in patients with primary biliary cirrhosis (PBC) and b) to investigate the relationship between leptin levels and liver fibrosis stage in a cohort of patients with PBC.. Serum leptin levels were evaluated through radioimmunoassay in 30 patients with PBC (mean age: 37.2 +/- 11.0 years; range:19-75) and in 29 controls matched for age and weight. Venous blood obtained after a 12-hour fast was centrifuged in EDTA tubes. Weight, height and body mass index (BMI) were measured using standard methods. Hepatitis C virus RNA was determined using qualitative and quantitative polymerase chain reaction. In all patients liver biopsies were performed and the degree of fibrosis and extent of inflammatory infiltrate were evaluated.. Plasma leptin levels in patients with PBC were lower than those obtained in control subjects (p<0.0001). No significant differences were found between the two groups in age, weight, height, BMI or body fat index. There was a clear increase in serum leptin levels according to histological stage of PBC (stage I: 2.1 ng/ml; stage II: 4.3 ng/ml; stage III: 5.3 ng/ml; stage IV: 12.1 ng/ml; p<0.01). The present study demonstrates the correlation between leptin and stage of liver fibrosis in a cohort of patients with PBC, providing further evidence of the involvement of leptin in the process of liver fibrosis.

Topics: Adult; Aged; Biopsy; Body Mass Index; Female; Humans; Leptin; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Radioimmunoassay; Severity of Illness Index

The recently discovered peptide hormone ghrelin mainly produced in gastric oxyntic cells may act as a counterpart to leptin in the regulation of food intake and fat utilization. Leptin, involved in the stimulation of proinflammatory cytokines and catabolic energy balance, is elevated in patients with liver cirrhosis. In the present study, we evaluated serum ghrelin and bound leptin levels in patients with primary biliary cirrhosis (PBC) in relation to C-peptide and glucose concentration.. In 22 female patients with PBC (Child-Pugh stage A) and in 36 female controls we measured serum ghrelin, bound leptin, and C-peptide levels using specific immunoassays.. In comparison to controls serum bound leptin levels were significantly higher in patients with PBC ( p < 0.01) whereas serum ghrelin levels were decreased compared to the control group ( p < 0.01). In parallel, C-peptide concentrations were increased ( p < 0.01) with no significant change in circulating glucose levels.. Our data confirm in PBC patients that serum bound leptin levels are increased and clearly show a parallel decrease in serum ghrelin concentrations acting as a physiological counterpart to leptin. Furthermore, we suggest that these changes are linked to the insulin resistance observed in our patients.

Topics: Female; Ghrelin; Humans; Leptin; Liver Cirrhosis, Biliary; Middle Aged; Peptide Hormones; Reference Values

Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyse fatigue in CHC and to determine its relationship with disease activity, resting energy expenditure (REE), circulating leptin, and tumour necrosis factor alpha (TNF-alpha).. Seventy eight CHC patients, 22 healthy controls, and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-alpha. All subjects completed the fatigue impact scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients.. Thirty eight of 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of patients was significantly higher than that of controls (53.2 (40.1) v 17.7 (16.9); p<0.0001) and was more pronounced in females (p=0.003). Leptin was increased significantly in CHC patients compared with controls (15.4 (20.7) v 6.4 (4.1) ng/ml; p<0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (r=0.30, p=0.01). This correlation increased when the physical domain of fatigue was included (r=0.39, p=0.0009). Furthermore, a similar positive correlation was found in PBC patients (r=0.56, p=0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load, or the METAVIR score in CHC patients.. Fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.

Topics: Adult; Body Composition; Fatigue; Female; Hepatitis C, Chronic; Humans; Leptin; Liver Cirrhosis, Biliary; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Surveys and Questionnaires; Tumor Necrosis Factor-alpha

The role of leptin in anorexia associated with liver cirrhosis remains controversial. The aim of this study was to quantify the serum leptin level in patients with hepatocellular or cholestatic liver disease and to assess its relationship with serum insulin, body mass index, and serum lipoproteins. The study population included 30 women, 15 with chronic hepatocellular liver disease and 15 with primary biliary cirrhosis; severity of disease was determined by Child-Pugh and histological criteria, respectively. Ten healthy, age-matched women served as controls. Levels of serum leptin and insulin were determined by radioimmunoassay. Mean serum leptin level was significantly lower in the primary biliary cirrhosis group compared to both the control (P < or = 0.05) and the hepatocellular groups (P < or = 0.05). Serum leptin level strongly correlated with body mass index in the hepatocellular group (P < 0.0001) and the controls (P < 0.001), but not in the primary biliary cirrhosis group; it showed no correlation with severity of liver disease. A positive correlation was found between serum leptin and serum cholesterol (P = 0.02), low density lipoprotein (P = 0.01), and triglycerides (P = 0.04) in the hepatocellular group and in the controls between serum leptin and serum high density lipoproteins (P = 0.01). Serum leptin is low in patients with primary biliary cirrhosis. The combined findings of normal insulin response less insulin resistance, and lower serum leptin level in primary biliary cirrhosis compared to hepatocellular liver disease may indicate that serum leptin is merely a passive marker and not a cause of anorexia in liver disease.

Topics: Anorexia; Cholesterol; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Insulin; Leptin; Lipoproteins, LDL; Liver Cirrhosis, Biliary; Middle Aged; Triglycerides