leptin and Liver-Cirrhosis--Alcoholic

Liver transplantation is the only curative treatment available for patients with end-stage alcoholic liver disease. As different studies showed a significant association between leptin plasma levels, gene methylation patterns and the extent of craving in alcohol-dependent patients, we investigated the effect of liver transplantation on leptin expression and promoter methylation.. The present study shows that in alcohol-dependent patients with liver cirrhosis leptin is significantly higher before liver transplantation and decreases significantly after transplantation. Alcohol-dependent patients on the waiting list had significantly higher leptin promoter methylation values than patients who underwent liver transplantation for other reasons than alcoholic liver disease.. Only plasma of 118 and peripheral blood mononuclear cells of 121 patients were used: healthy controls (C, n = 24/22), alcohol-dependent patients without ethyltoxic liver cirrhosis (AD, n = 24/22), patients after liver transplantation for other reasons than ethyltoxic liver cirrhosis (C-Tx, n = 18/21), alcohol-dependent patients suffering from ethyltoxic liver cirrhosis on the transplantation waiting list (Pre-Tx, n = 30/28) and patients with prior ethyltoxic liver cirrhosis after liver transplantation (Post-Tx, n = 22/28).. Leptin protein was significantly elevated in the pre-transplantation cohort when compared to post-transplantation and alcohol-dependent cohorts. Furthermore, leptin promoter methylation was higher in ethyltoxic patients before transplantation compared to non-ethyltoxic patients after transplantation, but not when compared to ethyltoxic patients after transplantation. C-Tx had lower methylation values than all other groups except for Post-Tx.. Our study outlines the role of leptin protein levels as a marker for AD-related liver damage, contrasting it from AD without severe liver damage. With regard to the results of the methylation analysis, inflammation of the liver appears to cause mechanisms of leptin regulation to deviate from transcriptional regulation. Our data also suggest that leptin regulation is altered in ethyltoxic liver disease when compared to liver cirrhosis caused by other pathologies.

Topics: Adult; Aged; Alcoholism; Biomarkers; Biomedical Research; Female; Forecasting; Gene Expression; Humans; Leptin; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Methylation; Middle Aged

The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels.. Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness.. Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes.. These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.

Topics: Adult; Aged; Anthropometry; Blood Glucose; Body Mass Index; Female; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Hypoglycemic Agents; Insulin; Leptin; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Risk Factors; Severity of Illness Index

To determine serum leptin levels in alcoholic liver cirrhosis and the relationship with gender, nutritional status, liver function, energy metabolism, inflammatory state and refeeding.. Thirty-seven hospitalized alcoholic cirrhotic patients (M/F: 24/13), 27 hospitalized patients at risk of malnutrition but with normal liver function (M/F: 15/12) as control patients, and 31 healthy control subjects (M/F: 17/14) participated.. Liver function was assessed from Child-Pugh classification; anthropometric parameters and resting energy expenditure (REE) were measured; caloric intake was evaluated over 5 days; and serum leptin and insulin were assayed. The same protocol was performed after 1 month refeeding in 22 patients. Healthy subjects were studied as controls for anthropometric parameters and serum leptin levels.. Serum leptin levels were higher in male cirrhotic patients than in the other two male groups (P=0.0079) and in the same range in the female groups. They were higher in female than in male subjects in the three groups. In female cirrhotic patients, logarithmically transformed serum leptin levels correlated significantly with fat mass (P=0.0043), insulin levels (P=0.0072), REE (P=0.0133), bilirubin levels (P<0.0001), prothrombin time (P=0.0003) and Pugh score (P=0.0266) in simple regression analysis and with insulin levels (P=0.0137), but not with fat mass (P=0.0761), Pugh score (P=0.4472) and REE (P=0.4576) in multiple regression analysis. In the male cirrhotic and control patients, log (leptin) levels correlated with CRP (C reactive protein) (r=0.365, P=0.0223). Log (leptin) levels did not correlate with caloric intake in any of the groups. Leptin levels (P<0.05) and fat mass (P<0.02) increased with refeeding while liver function improved (P<0.01).. There is a gender difference in regulation of serum leptin level in alcoholic liver cirrhosis. Insulin level is the best determinant of leptin level in female patients while inflammatory state related to alcoholic hepatitis seems to have a greater influence in male patients. Although leptin levels positively correlated with REE in female patients, there is no evidence that leptin reduces caloric intake and fat stores in these patients.

Topics: Adult; C-Reactive Protein; Energy Metabolism; Female; Humans; Insulin; Leptin; Liver Cirrhosis, Alcoholic; Liver Function Tests; Male; Middle Aged; Nutrition Disorders; Nutritional Status; Sex Factors

Little information is available on the involvement of leptin in clinical conditions associated with malnutrition, such as liver cirrhosis. The behaviour of serum leptin in patients with different Child-Pugh score, post-hepatitis liver cirrhosis and insulin sensitivity has therefore been investigated and compared with that in alcoholic Child C patients.. Sixty-four patients, aged 51 to 62 years, with different degrees of post-hepatitis cirrhosis or Child C alcoholic cirrhosis were compared with 15 age-matched control subjects. Body composition was estimated by skinfold thickness. Serum leptin, glucose and insulin were assayed.. In post-hepatitis patients a significant reduction in leptin levels was observed as the Child-Pugh score worsened (men: 2.94+/-1.61 in Child C vs 6.78+/-2.49 ng/ml in controls, p<0.001; women: 4.14+/-0.66 in Child C vs 16.16+/-3.90 ng/ml in controls, p<0.02). Conversely, only the men with alcoholic liver cirrhosis showed a significant difference in leptin concentration compared to controls (8.5+/-2.1 vs 16.4+/-7.9 kg, p<0.05). In particular, Child C, alcoholic cirrhotic women had a significantly (p=0.03) higher level of leptin than post-hepatitis matched women. A positive correlation was observed between leptin and fat mass (men R2=0.59, p<0.0001 and women R2=0.65, p<0.0001). While fasting levels of serum leptin correlated significantly with insulin concentrations in controls, a similar relationship was not observed in the cirrhotic population, which displayed higher insulin concentrations than controls.. In contrast to findings in alcoholic cirrhotic women, low leptin values in post-hepatitis cirrhotic patients mainly represent the expression of a reduced fat mass.

Topics: Adipose Tissue; Fasting; Female; Hepatitis B; Hepatitis C; Humans; Insulin Resistance; Leptin; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Organ Size; Reference Values

Leptin is a cytokine peptide that decreases appetite and thereby food intake and increases energy expenditure. It is produced in fat cells, but recent animal experiments have shown expression of leptin in modified stellate hepatic cells. Because a change in circulating leptin in cirrhosis could be caused by an altered production rate, altered disposal rate, or both, the present study was undertaken to identify regions of leptin overflow into the blood stream and regions of leptin extraction. Patients with alcoholic cirrhosis (n = 16) and control patients without liver disease (n = 12) were studied during catheterization with elective blood sampling from different vascular beds. Blood samples for leptin determination (radioimmunoassay) were taken simultaneously from artery/hepatic vein, artery/renal vein, artery/iliac vein, and artery/cubital vein. Patients with cirrhosis had significantly increased circulating leptin (7.3 vs. control 2.6 ng/mL, P <.002) that correlated directly to ascitic-free body mass index (r = 0.71, P <.005). A significant renal extraction ratio of leptin was observed in control patients (0. 16) and in patients with cirrhosis (0.07), but the latter value was significantly lower than in the control patients (-44%, P <.05) and inversely correlated to serum creatinine (r = -0.60, P <.05). A significant, but equal, hepatosplanchnic extraction of leptin was observed in cirrhotic patients and control patients (0.08 vs. 0.07). In patients with cirrhosis a significant cubital venous-arterial difference in leptin was observed, but not in control patients. The iliac venous/arterial leptin ratio was significantly above 1.0 in both groups and of similar size (1.16 vs. 1.15), but a higher difference in concentration was found in the cirrhotic patients (+33%, P <.05). The spillover rates of leptin in cirrhotic patients may be even higher than estimated from the increased systemic veno-arterial gradients. In conclusion, the elevated circulating leptin in patients with cirrhosis is most likely caused by a combination of decreased renal extraction and increased release from subcutaneous abdominal, femoral, gluteal, retroperitoneal pelvic, and upper limb fat tissue areas. The hepatosplanchnic bed drained through hepatic veins could not be identified as a source of increased circulating leptin in cirrhosis, but a contribution by the portosystemic collateral flow cannot be excluded.

Topics: Adult; Aged; Bilirubin; Blood Glucose; Blood Pressure; Cardiac Output; Energy Intake; Female; Hemodynamics; Hepatic Artery; Hepatic Veins; Humans; Leptin; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Proteins; Radioimmunoassay; Reference Values; Renal Artery; Renal Circulation; Renal Veins; Splanchnic Circulation; Vascular Resistance

Leptin is a peptide that decreases food intake and increases energy expenditure. It is produced in fat cells, is stimulated by cytokines, and its levels in serum are higher in females. Because anorexia, hypermetabolism, and elevated cytokine levels are frequently observed in cirrhosis, we hypothesized that the serum leptin level would be elevated in cirrhosis. The aim of this study was to investigate the relationship of serum leptin to gender, body composition, and tumor necrosis factor (TNF).. Male (n = 18) and female (n = 10) abstinent alcoholic cirrhotic patients were studied and compared with control subjects (15 male and 8 female). Fat mass, fat-free body mass, and body cell mass were calculated by using H2[18O] and bromide dilution methodology. Serum leptin and TNF concentrations were measured by immunoassays.. Fat mass was decreased only in male cirrhotics (P < 0.05), whereas body cell mass was decreased in both male and female cirrhotics (P < 0.01). Leptin levels were elevated in female (P < 0. 001) but not male cirrhotics compared with controls. When expressed per kilogram of fat mass, leptin was elevated in both male (P < 0. 01) and female (P < 0.01) cirrhotics. Women in both cirrhotic and control groups had higher leptin levels than men. TNF was elevated in both male and female cirrhotics and did not correlate with leptin levels.. Cirrhotics have elevated serum leptin levels, which are related to both gender- and gender-dependent alterations in body composition.

Topics: Adult; Body Composition; Female; Humans; Leptin; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Proteins; Reference Values; Sex Characteristics; Tumor Necrosis Factor-alpha