leptin and Hepatitis-C--Chronic

Obesity and the metabolic syndrome (MS) are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although rare cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to nonalcoholic fatty liver disease (NAFLD). Moreover, MS and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with MS to improve the screening guidelines and develop prophylactic treatments in this setting.

Topics: Adiponectin; Carcinoma, Hepatocellular; Diabetes Complications; Disease Progression; Fatty Liver; Hepatitis C, Chronic; Humans; Leptin; Liver Neoplasms; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Risk Factors

The risk factors for hepatocellular carcinoma (HCC) development have been established, and include chronic hepatitis B and C, heavy alcohol consumption, and aflatoxins. In fact, 5%-30% of patients with HCC still lack a readily identifiable risk factor. It has been reported that the majority of ''cryptogenic'' HCC may be attributed to nonalcoholic fatty liver disease, the hepatic presentation of the metabolic syndrome (MS). Obesity is associated with the development of the MS. Recently, adipose tissue has been considered as an endocrine organ because of its capacity to secrete a variety of cytokines, which are collectively known as the adipokines. Leptin, the product of the obese gene, is mainly produced by adipose tissue. Since leptin was first characterized in 1994, accumulated literature has demonstrated the involvement of this adipokine in several areas of human physiology. After binding to its receptor, leptin initiates a cascade of signaling events and subsequent cellular effects. In addition to being the regulatory mediator of energy homeostasis, several in vitro studies have demonstrated the fibrogenic role of leptin in the liver. Furthermore, the deregulated expression of leptin and its receptor have been demonstrated to be associated with a variety of metabolic disorders as well as human cancers. Most importantly, direct evidence supporting the inhibitory and/or activating role of leptin in the process of carcinogenesis and progression of human HCC has been accumulating rapidly. This review aims to provide important insights into the potential mechanisms of leptin in the development of HCC. Hopefully, further investigations will shed light on a new therapeutic target in HCC.

Topics: Aflatoxins; Carcinoma, Hepatocellular; Fatty Liver; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Leptin; Liver Neoplasms; Metabolic Syndrome; Receptors, Leptin; Risk Factors; Signal Transduction

Leptin and adiponectin, the main metabolic products of adipose tissue, have been implicated in a wide spectrum of human diseases. Given the frequent presence of hepatic steatosis in several chronic liver diseases, there is currently increasing interest in the role of these adipokines in the development of hepatic steatosis and also in necroinflammation and fibrosis, mostly in patients with nonalcoholic fatty liver disease or chronic hepatitis C. According to experimental data, reduced adiponectin levels and increased leptin levels associated with leptin resistance, which are usually observed in obese patients with or without metabolic syndrome, may result in fat accumulation in the liver and in the enhancement of liver inflammation and mostly fibrogenesis. Increased leptin and decreased adiponectin serum levels have been detected initially in patients with nonalcoholic steatohepatitis and more recently in patients with chronic hepatitis C compared to healthy controls in most but not all studies, while the data on the associations between these adipokine levels and the severity of hepatic steatosis or fibrosis are still rather conflicting. However, several potential confounding parameters were not evaluated in all studies. Therefore, the associations between adipokines and liver histological lesions and their effects on liver cells should be evaluated further in prospective, carefully designed studies, including larger cohorts of patients with detailed assessment of metabolic and other potential confounding factors.

Topics: Adiponectin; Chronic Disease; Fats; Fatty Liver; Hepatitis C, Chronic; Humans; Leptin; Liver; Liver Cirrhosis; Liver Diseases

The role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment.. We studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment.. A significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy.. Our data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.

Topics: Adolescent; Adult; Age Factors; Aged; Antiviral Agents; Biomarkers; Biopsy, Needle; Case-Control Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Immunohistochemistry; Interferon alpha-2; Interferon-alpha; Lamivudine; Leptin; Liver Function Tests; Male; Middle Aged; Multivariate Analysis; Probability; Prospective Studies; Recombinant Proteins; Reference Values; Ribavirin; Risk Factors; Severity of Illness Index; Sex Factors; Treatment Outcome

Leptin has a particular profibrogenic role in the liver. We investigated whether IFN-alpha influences leptin production in patients with chronic hepatitis B (CHB) and C (CHC). Leptin was determined in serial samples from 63 CHB and 42 CHC IFN-alpha treated patients. Furthermore, we evaluated whether leptin alterations were associated with patients' characteristics.. Sera were investigated at serial time-points using an enzyme-linked-immunosorbent-assay. Controls consisted of 36 patients with autoimmune liver diseases and 44 healthy patients.. Leptin levels before IFN-alpha administration were higher in CHB and CHC compared to healthy (P<0.004) and diseased controls (P=0.0001). In CHB patients, we observed a significant reduction of leptin during IFN-alpha treatment and lasting for up to 6 months after the end of treatment, followed by an increase reaching pretreatment levels at 1.5 years after stopping therapy. The pattern of leptin alterations was similar in CHC patients where leptin's decrease was more pronounced at 6 months after the end of treatment. Biochemical or virological response to treatment was not associated with leptin reduction in both groups.. This study provides information on leptin kinetics during IFN-alpha treatment and follow-up in CHB and CHC patients and suggests IFN-alpha as a potential inhibitor of leptin production.

Topics: Adult; Aged; Antiviral Agents; Female; Follow-Up Studies; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis, Autoimmune; Humans; Interferon-alpha; Leptin; Liver Cirrhosis; Male; Middle Aged; Prospective Studies; Sex Characteristics; Treatment Outcome

Leptin has recently been suggested to play a role in the pathogenesis of hepatic steatosis and steatohepatitis in the absence of viral infection. The aim of this study was to evaluate whether leptin levels are associated with hepatic steatosis in chronic hepatitis C.. Thirty-one patients (22 female, 9 male, mean age: 51 +/- 9) with histologically proven chronic hepatitis C were included in this prospective, controlled, observational, clinical study with blind outcome assessment. Patients with and without steatosis in liver biopsy served as each others' controls.. Chronic hepatitis C patients with (n=23) and without steatosis (n=8) were similar with respect to their serum glucose, lipid and leptin levels (p>0.05). Serum leptin levels were correlated with both patient factors, such as obesity and with liver enzymes, such as ALT, AST only in patients with steatosis. Chronic hepatitis C patients with or without steatosis had similar leptin levels of 6.3 +/- 2.5 and 4.9 +/- 2.5, respectively.. Leptin levels were well correlated with antropometrical parameters in chronic hepatitis C patients. Leptin levels were associated with evidence of impaired hepatic function in patients with chronic HCV related steatosis. Serum leptin may be a prognostic marker for patients with chronic HCV infection with steatosis.

Topics: Adult; Aged; Alkaline Phosphatase; Anthropometry; Bilirubin; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Leptin; Male; Middle Aged; Prospective Studies

To determine the role of nonspecific inflammation in the formation of IR and metabolic syndrome in patients with chronic hepatitis C.. The study included 205 patients with CHC aged 18 to 69 years. Patients with CHC are randomized into two groups depending on the presence of IR: group 1 - patients with a HOMA index ≥2.77, which corresponded to IR (n=110); group 2 (n=95). The levels of serum iron, C-reactive protein (CRP), serum ferritin and adipose tissue hormones [leptin, resistin, adiponectin and tumor necrosis factor-α (TNF-α)] were additionally investigated.. At all stages of development of IR, nonspecific inflammation was detected (according to ferritin, CRP and serum iron), increasing with increasing HOMA index [Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)] (Matthews D., 1985), metabolic syndrome and its components. In the analysis of indicators in patients with chronic hepatitis C with a body mass index <25 kg/m2, conjugacy of IR with low-intensity inflammation, high viral load and hypersecretion of TNF-α was detected.. Given the high predictor role of CRP indicators in predicting IR, it should be used as a surrogate screening marker of IR in patients with chronic hepatitis C and should be actively treated for violations.

Topics: Adiponectin; Adolescent; Adult; Aged; Hepatitis C, Chronic; Humans; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Random Allocation; Young Adult

There are millions of chronic hepatitis C (CHC) virus-infected patients who have been treated with a combination therapy (interferon and ribavirin) and have achieved a virological response (SVR) worldwide. The aim of this study is to evaluate the risk factors for de-novo diabetes mellitus in CHC patients treated with combination therapy (interferon and ribavirin) and have achieved an SVR.. A total of 214 nondiabetic CHC patients with SVR and baseline homeostasis model assessment (HOMA) less than or equal to 2 were divided into group A, which included 108 patients with a BMI less than 25, and group B, which included 106 patients with a BMI of at least 25 and less than 30. HOMA insulin resistance (IR) and BMI were measured at the baseline, at achievement of an SVR, and 1 year after achievement of an SVR. Leptin levels were assessed at baseline and 1 year after achievement of an SVR in patients with increased BMI.. One year after SVR, 36 (33.33%) patients from group A developed increasing BMI with no significant changes in HOMA versus that at SVR (P=0.53), but showed a significant reduction versus baseline HOMA (P=0.02). In group B, 68 (64.1%) patients showed increased BMI of at least 25, with a significant increase in HOMA versus that at SVR (P=0.02), and with no significant reduction versus baseline HOMA (P=0.44). In group B, serum leptin showed a significant reduction 12 months after achievement of an SVR versus baseline in patients with increased BMI. Six patients from group B with increased BMI after 1 year developed de-novo IR and type two diabetes mellitus.. In nondiabetic CHC patients with SVR and baseline BMI of at least 25, the post-SVR increase in BMI predisposed to an increase in HOMA-IR and could be considered a predisposing factor for diabetes mellitus.

Topics: Adult; Antiviral Agents; Biomarkers; Blood Glucose; Body Mass Index; Diabetes Mellitus; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Interferon alpha-2; Interferon-alpha; Leptin; Male; Middle Aged; Polyethylene Glycols; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Ribavirin; Risk Factors; Sustained Virologic Response; Time Factors; Treatment Outcome

The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown.. A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels.. Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and multivariate analyses showed that sex (pre- and post-therapy, p<0.001), body mass index (BMI) (pre- and post-therapy, p<0.001), and C3 levels (pre-therapy, p = 0.027; post-therapy, p = 0.02) were independently associated with leptin levels with or without HCV infection. Pre-therapy BMI, total cholesterol (TC), C4 levels, and the rs12979860 genotype were independently associated with pre-therapy C3 levels in all patients. Post-therapy BMI, alanine aminotransferase, TC, C4 levels, white blood cell counts, and hepatic steatosis were independently associated with the post-therapy C3 levels of SVR patients. Compared with pre-therapy levels, SVR patients showed higher 24-week post-therapy C4 (20.32+/-7.30 vs. 21.55+/-7.07 mg/dL, p<0.001) and TC (171.68+/-32.67 vs. 186.97+/-36.09 mg/dL, p<0.001) levels; however, leptin and C3 levels remained unchanged after therapy in patients with and without an SVR.. Leptin and C3 may maintain immune and metabolic homeostasis through association with C4 and TC. Positive alterations in C4 and TC levels reflect viral clearance after therapy in CHC patients.

Topics: Adult; Aged; Alanine Transaminase; Antiviral Agents; Body Mass Index; Complement C3; Complement C4; Complement System Proteins; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Homeostasis; Humans; Interferons; Interleukins; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; RNA, Viral; Sustained Virologic Response

TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype.

Topics: Adiponectin; Adult; Aged; Biomarkers; Female; Hepatitis C, Chronic; Humans; Insulin Resistance; Interferons; Interleukin-6; Interleukins; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha; Young Adult

Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients.. Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated.. A serum AIM level of ≥ 1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103-28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ≥ 8.6 ng/ml was independently associated with the presence of hepatic steatosis (≥ 5%) (OR, 6.195; 95% CI, 1.409-27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively.. High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism.

Topics: Adiponectin; Adult; Age Factors; Aged; Alanine Transaminase; Biomarkers; Fatty Liver; Female; gamma-Glutamyltransferase; Glucose Tolerance Test; Hepatitis C, Chronic; Homeostasis; Humans; Hyaluronic Acid; Insulin Resistance; Leptin; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Receptors, Scavenger; Resistin; Serum Albumin; Severity of Illness Index

Hepatitis C virus (HCV) infection has major health impact worldwide and is a significant cause of chronic liver disease. In Egypt, HCV is highly endemic (up to 15% of the population); 91% of the patients are infected with genotype 4. Searching for new predictors of response to therapy is mandatory to decrease the cost and the adverse effects of current therapy.. The aim of this study was to clarify the usefulness of serum leptin, adiponectin, and insulin resistance (IR) as predictors of response to treatment in hepatitis C virus genotype 4 (HCVG4).. One hundred patients with chronic HCVG4 who were candidates for treatment with pegylated interferon α and ribavirin were included in the study. Age, sex, and BMI were determined, and quantitative HCV PCR, assessment of serum leptin, adiponectin, IR, and pretreatment liver profile, and liver biopsy were performed.. The male to female ratio was 68/32; the mean age of the patients was 40.9 ± 7.8 years and BMI was 28.3 ± 10 kg/m. Sustained virological response (SVR) was achieved by 56% of the patients. On performing logistic regression, BMI [odds ratio (OR) 6.5; P=0.004], serum leptin (OR 27.8; P ≤ 0.001), aspartate aminotransferase (OR 1.06; P ≤ 0.001), IR (OR 1.15; P ≤ 0.001), histological activity index (OR 1.77; P=0.006), and fibrosis (OR 2.93; P=0.001) were found to be independent negative predictors of SVR, whereas serum adiponectin (OR 0.74; P ≤ 0.001) was found to be an independent positive predictor of SVR. Pretreatment adiponectin (cutoff 13.75; sensitivity 92.86%; specificity 86.86%) shows area under the curve of 0.879 (95% confidence interval 0.802-0.956; P<0.001) and insignificant area under the curve for leptin or IR.. BMI, pretreatment high leptin levels, and IR are negative predictors for SVR and pretreatment low adiponectin levels are an independent positive predictor for SVR in HCVG4.

Topics: Adipokines; Adiponectin; Adult; Antiviral Agents; Area Under Curve; Biomarkers; Biopsy; Body Mass Index; Chi-Square Distribution; Drug Therapy, Combination; Egypt; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Insulin Resistance; Interferon-alpha; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Phenotype; Predictive Value of Tests; Ribavirin; Risk Factors; RNA, Viral; ROC Curve; Treatment Outcome; Viral Load

The detection and diagnosis of hepatocellular carcinoma (HCC) at an early stage may significantly affect the prognosis of HCC patients. Thus, it is necessary to always identify novel putative markers for improving diagnosis. Hepatocarcinogenesis correlates with pathological hepatic angiogenesis. However, each tumor-induced angio-genetic process is influenced by the microenvironment through several pro- and anti-angiogenic factors released from tumor cells, tumor-associated inflammatory cells and/or from the extracellular matrix, and modulated by various signal pathways. In this study, we evaluated the profiling of angiogenic factors using Bio-Plex Pro™ Human Cancer Biomarker Panel 1, a 16-plex magnetic bead-based assay, in sera of patients with chronic hepatitis C (CHC) virus, liver cirrhosis (LC) and HCC. Our results demonstrated: i) high levels of hepatocyte growth factor (HGF) and prolactin only in LC and HCC patients, ii) high levels of soluble human epidermal growth factor receptor‑2 (sHER-2/neu; ErbB-2), sIL-6Ra, leptin (LEP) and platelet endothelial cell adhesion molecule‑1 (PECAM-1) in CHC, LC and HCC patients and iii) that sIL-6R correlated with the fibrosis stage in CHC patients, with Child‑Pugh score in those patients with LC and with tumor size in those patients with HCC, confirming that this protein may be used as a predictor of liver damage and of inflammatory process leading to fibrosis, cirrhosis, and subsequently to cancer. Moreover, an interactomic study conducted using the Ingenuity Pathway Analysis (IPA) software proved the existence of a correlation between 5 significant proteins [ErbB-2, sIL-6Ra, prolactin (PRL), HGF and LEP] which are involved in the same metabolic pathways.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Female; Hepatitis C, Chronic; Hepatocyte Growth Factor; Humans; Interleukin-6 Receptor alpha Subunit; Leptin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Prognosis; Prolactin; Receptor, ErbB-2

Fatigue is one of the most common presenting symptoms of chronic hepatitis C virus (HCV) infection. Its pathogenesis has been poorly investigated. Serum leptin levels are increased in cirrhosis and are suggested to have a role in the mediation of fatigue. This study was designed to assess possible association of serum leptin levels with fatigue and severity of liver disease in Egyptian patients with chronic hepatitis C infection.. Seventy patients and 20 control subjects participated in the study. They were subjected to clinical and laboratory assessment, the determination of serum leptin level by ELISA and the assessment of fatigue using the multidimensional assessment of fatigue (MAF) scale. Respondents are asked to reflect on fatigue patterns for the past week. The MAF is a revision of the Piper Fatigue Scale.. Fatigue was present in all patients (100%) and 13 subjects of the control group (65%). There was a highly significant statistical difference between cases and controls regarding the presence and severity of fatigue. Serum leptin level was significantly higher in cases (24.9±28) in comparison to the control subjects (14.8±8). Serum leptin was not related to severity of liver disease as assessed by the Child Pugh classification. Serum leptin levels were directly correlated to the severity of fatigue (p<0.01) in patients but not in the control subjects.. Fatigue is highly prevalent in Egyptian patients with chronic HCV infection. Leptin might play a role in the mediation of fatigue in those patients drawing attention to biological basis of one of the most common symptoms facing clinician dealing with this problem.

Topics: Adult; Aged; Ascites; Aspartate Aminotransferases; Bilirubin; Body Mass Index; Case-Control Studies; Fatigue; Female; Hepacivirus; Hepatitis C, Chronic; Humans; International Normalized Ratio; Leptin; Male; Middle Aged; Severity of Illness Index; Statistics, Nonparametric; Surveys and Questionnaires

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

Fatigue is an important determinant of altered quality of life in patients affected by chronic hepatitis C or the irritable bowel syndrome (IBS).. In this study, we aimed at determining the contributory role of plasma levels of leptin and carnitine on fatigue in chronic hepatitis C and IBS.. We enrolled 81 patients with chronic hepatitis C, 42 with IBS and 44 healthy subjects. Fatigue was evaluated using the Fatigue Impact Scale questionnaire. Body composition was assessed through impedance analysis. Plasma carnitine and leptin were measured.. Fatigue scores were significantly more elevated in patients with chronic hepatitis C and IBS than in healthy subjects. Patients with chronic hepatitis C but not IBS, had significant lower plasma levels of total and free carnitine adjusted for fat mass compared with healthy subjects. In patients with chronic hepatitis C and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine. Levels of free carnitine were significantly and independently associated with the severity of fatigue in patients with chronic hepatitis C [OR=2.019, P=0.02, CI 95% (1.01-1.23)].. In patients with chronic hepatitis C, the severity of fatigue is associated with a low level of carnitine, suggesting that an oral supplementation may be effective to relieve fatigue in chronic hepatitis C. The underlying mechanism of fatigue in IBS does not seem to involve carnitine.

Topics: Adult; Aged; Aged, 80 and over; Body Composition; Carnitine; Case-Control Studies; Electric Impedance; Fatigue; Female; Hepatitis C, Chronic; Humans; Irritable Bowel Syndrome; Leptin; Male; Middle Aged; Quality of Life; Surveys and Questionnaires

The aim of this prospective study was too asses the frequency and clinical significance of metabolic syndrome (MS), insulin resistance (IR) and hepatic steatosis in 114 patients with chronic hepatitis C (HCV) genotype 1. MS was found in 47% and IR in 50% of the cases. Diagnosis of IR in patients without MC and marked fibrosis supported the role of HCV in the development of metabolic abnormalities. Hepatic steatosis was found in 38% of the patients and the degree of steatosis significantly correlated with that of fibrosis. Obesity, IR, steatosis and liver cirrhosis were independent negative predictors of the response to the treatment with peginterferon alpha and ribavirin.

Topics: Adult; Antiviral Agents; Fatty Liver; Female; Genome, Viral; Hepacivirus; Hepatitis C, Chronic; Hepatocytes; Humans; Insulin Resistance; Interferon alpha-2; Interferon-alpha; Leptin; Liver Cirrhosis; Male; Metabolic Syndrome; Middle Aged; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Ribavirin; Severity of Illness Index; Treatment Outcome

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

Leptin is a hormone secreted by adipocytes that plays an important role in regulating appetite and energy expenditure. Our aim was to evaluate serum leptin level in hemodialysis (HD) patients with or without chronic liver disease (CLD) and study the relationship between serum leptin level and bone mineral density in these groups of patients.. we recruited 20 healthy volunteers as controls (group I), 20 patients on regular HD with normal liver function (group II), 20 CLD patients with normal kidney function (group III) and 20 patients on regular HD with CLD (group IV). We measured serum calcium, phosphorus, parathyroid hormone (PTH), total alkaline phosphatase (ALP), serum leptin, 24-hours urinary hydroxyproline and bone mineral density (BMD) of the lumber spine and femoral neck by DEXA scan.. Serum leptin level was significantly higher (p < 0.001) in HD patients and CLD patients compared to controls. Its level was also significantly elevated in HD patients without liver disease (group II) compared to patients with CLD who had no renal failure (group III). Urinary hydroxyproline level was increased in both HD patients and CLD patients. We detected a positive correlation between serum leptin level and urinary hydroxyproline in all patient groups. There was a significant decrease in BMD in HD and CLD patients. BMD was significantly lower in HD patients without CLD compared to HD patients with CLD. There was a significant negative correlation between serum leptin level and BMD in CLD patients without renal disease but not in other groups (r = - 0.6, P = 0.01).. Serum leptin is elevated in HD patients with or without liver disease and in CLD patients. Serum leptin level is inversely correlated with BMD in CLD patients without renal disease.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Bone Density; Chronic Disease; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Hydroxyproline; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Schistosomiasis; Young Adult

To determine the associations between leptin and ghrelin concentrations and sustained virological response (SVR) in chronic hepatitis C patients with steatosis.. We retrospectively assessed 56 patients infected with hepatitis C virus (HCV) genotype-1 and 40 with HCV genotype-3. Patients with decompensated cirrhosis, and those with other causes of chronic liver disease, were excluded. Serum HCV-RNA concentrations were measured before the initiation of treatment; at weeks 12 (for genotype 1 patients), 24 and 48 during treatment; and 24 wk after the end of treatment. Genotype was determined using INNO-LIPA HCV assays, and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay. Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild, moderate, or severe, according to the Brunt classification.. Overall, SVR was positively related to the presence of genotype-3, to biopsy-determined lower histological stage of liver disease, and lower grade of steatosis. Patients ≥ 40 years old tended to be less responsive to therapy. In genotype-1 infected patients, SVR was associated with a lower grade of liver steatosis, milder fibrosis, and an absence of insulin resistance. Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concentrations at baseline, with significant increases as the severity of steatosis worsened, whereas those who achieved SVR had higher ghrelin concentrations. In genotype-3 infected patients, SVR was associated only with fibrosis stage and lower homeostasis model assessment insulin resistance at baseline, but not with the degree of steatosis or leptin concentrations. Genotype-3 infected patients who achieved SVR showed significant decreases in ghrelin concentration at end of treatment. Baseline ghrelin concentrations were elevated in responders of both genotypes who had moderate and severe steatosis.. Increased serum leptin before treatment may predict non-SVR, especially in HCV genotype-1 infected patients, whereas increased ghrelin may predict SVR in genotype-1.

Topics: Adult; Antiviral Agents; Fatty Liver; Female; Genotype; Ghrelin; Hepacivirus; Hepatitis C, Chronic; Humans; Leptin; Male; Retrospective Studies; RNA, Viral

It is unclear whether angiogenesis merely represents a homeostatic mechanism aimed at ensuring an adequate oxygen supply or one that exerts an additional pathogenic role leading to liver damage in chronic hepatitis. Chronic hepatitis C (CHC) patients present a proangiogenic profile of angiogenic markers. Adipokines not only regulate adipose tissue and glucose metabolism, but also influence inflammation, fibrogenic process and production of proangiogenic factors. On the basis of this evidence we aimed to assess the number of new blood vessels in lobules and portal tracts in the liver and evaluate the relationship between angiogenesis intensity and serum adipokine concentrations in CHC. Our study showed a positive association between serum vaspin and angiogenesis intensity in portal tracts and lobules in CHC patients (r = 0.41, p = 0.04; r = 0.46, p = 0.03; respectively). Serum visfatin was found to be negatively related to angiogenesis in portal tracts and lobules but only in females (r = -0.76, p = 0.03; r= -0.95, p < 0.001; respectively). In conclusion, the role of some adipokines in liver angiogenesis seems to be different in females than in males. Serum vaspin concentration seems to reflect intensity of liver angiogenesis in CHC. Further studies are necessary to better determine the role of adipokines in new blood vessel formation in CHC.

Topics: Adipokines; Adiponectin; Adult; Chemokines; Cytokines; Female; Hepatitis C, Chronic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Liver; Male; Middle Aged; Neovascularization, Pathologic; Nicotinamide Phosphoribosyltransferase; Obesity; Serpins; Sex Factors; Young Adult

To estimate the incidence and clinical value of metabolic syndrome, insulin resistance, and steatosis in patients with chronic hepatitis C (CHC) caused by its virus genotype 1.. One hundred and fourteen patients (67 men and 47 women; mean age 44.9 +/- 13.3 years) were examined.. There were high incidence rates of metabolic syndrome (47.2%) and insulin resistance (50%), in the genesis of which the host-virus interaction is discussed. There was an independent correlation of the insulin resistance and elevated leptin levels with abdominal obesity and hepatic steatosis; however, these indicators did not correlate with the stage of fibrosis. At the same time hepatic steatosis (found in 38% of the patients) and its degree correlated with the stage of fibrosis. Thirty-four of 66 (54.5%) patients receiving antiviral therapy achieved a stable virological response.. Obesity, hyperglycemia, and significant insulin resistance along with the stage of hepatic cirrhosis are independent cofactors that determine no treatment response.

Topics: Adult; Antiviral Agents; Diabetes Mellitus, Type 2; Fatty Liver; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Incidence; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Prospective Studies; Treatment Outcome

In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR 1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01-1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV.

Topics: Adipokines; Adult; Cohort Studies; Diabetes Complications; Disease Progression; Female; Hepatitis C, Chronic; Humans; Insulin Resistance; Kaplan-Meier Estimate; Leptin; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Prediabetic State; Regression Analysis; Risk

Hepatic steatosis and fibrosis are common histological findings in patients with chronic hepatitis C virus (HCV) infection. In this study we sought to determine whether serum levels of three adipokines (leptin, adiponectin and resistin) show any biochemical correlation with hepatic steatosis and fibrosis in patients with chronic HCV infection.. We examined a total of 51 patients with chronic HCV infection (22 males and 29 females, mean BMI: 27.4+/-5kg/m(2)) and 24 healthy control subjects (10 males and 14 females, mean BMI: 23.2+/-3kg/m(2)). Liver steatosis and fibrosis were scored on biopsies. Serum levels of leptin, adiponectin and resistin were determined by ELISA.. HCV genotypes were 1b in 41 patients (80.4%), 3a in three patients (5.9%), 2a in two patients (3.9%), 1a in two patients (3.9%), 1c in one patient (2%), and 2b in one patient (2%). Serum levels of leptin, resistin, and the leptin-to-adiponectin ratio were significantly higher in patients with chronic HCV infection than in controls. Steatosis and fibrosis were detected in 33.3% and 70.5% of chronic HCV patients, respectively. No significant association with serum adipokine levels and degree of steatosis was evident. Low serum levels of resistin were associated with the presence of fibrosis independently of potential confounders.. Patients with chronic HCV infection display elevated levels of adipokines in their sera. Reduced concentrations of resistin may be a biochemical marker of fibrosis in this patient group.

Topics: Adiponectin; Adult; Body Mass Index; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged; Resistin

Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis.. We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells.. Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells.. In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

Topics: Adult; Blood Glucose; Connective Tissue Growth Factor; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Immediate-Early Proteins; Immunoblotting; Immunohistochemistry; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Liver Cirrhosis; Male; Middle Aged; Switzerland

Steatosis is common in hepatitis C virus (HCV)-infected patients and likely accelerates fibrosis progression. Leptin, the peptide product of the obesity gene (ob), has been implicated in hepatic fibrogenesis; circulating levels of leptin correlate with body fat mass. The objective of the present study was to determine the clinical and histological correlates of serum leptin in HCV-infected patients, and to determine its utility in predicting liver histological lesions.. In 62 patients with chronic HCV, serum leptin was measured using a commercially available immunoassay. Associations between leptin, metabolic parameters, and severe hepatic fibrosis (stages 2 to 4) and steatosis (30% or greater) were determined. The utility of leptin in predicting liver histology was determined using receiver operating characteristic (ROC) curves.. The median body mass index (BMI) was 23.2 kg/m2 (range 17.7 kg/m2 to 35.6 kg/m2); 16% of patients (n=10) had HCV genotype 3. Severe fibrosis and steatosis were present in 23% and 13% of patients, respectively. Leptin was strongly correlated with the BMI, and its levels were higher in women. BMI-corrected leptin levels were not independently associated with severe fibrosis but were significantly associated with steatosis (OR of 1.07; 95% CI 1.01 to 1.04). On it own, leptin was poorly predictive of severe steatosis (area under the ROC curve was 0.64; 95% CI 0.42 to 0.87). However, its accuracy improved with the addition of HCV genotype (area under the ROC curve was 0.86; 95% CI 0.72 to 1.00; P=0.07).. As observed in the non-HCV setting, serum leptin correlates with BMI; higher leptin levels are found in women than men with chronic HCV. Serum leptin is a poor predictor of HCV-related fibrosis but may play a role in predicting steatosis when combined with HCV genotype.

Topics: Adult; Aged; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged; Predictive Value of Tests; Sex Factors

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).. 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.

Topics: Adiponectin; Adult; Biopsy; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Insulin Resistance; Interleukin-6; Leptin; Liver; Liver Cirrhosis; Male; Middle Aged; Patient Selection; Reference Values; Tumor Necrosis Factor-alpha; Viral Load

To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C.. A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon (IFN) from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus (HCV) RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy. Patients who remained positive for HCV RNA at the end of IFN treatment were defined as resistant to IFN therapy. Sex, age, body mass index (BMI) (> or =25 vs <25), complication of diabetes mellitus, serum leptin level (> or =8.0 microg/L vs < 8.0 microg/L), and the stage of liver fibrosis by needle biopsy (F1/F2 vs F3/F4) were examined.. Sustained response was achieved in 33 patients (23.7%), while others failed to show a response to IFN therapy. Overall, the factors associated with sustained antiviral effects were HCV-RNA load, HCV genotype, serum leptin level, and stage of liver fibrosis evaluated by univariate analysis. BMI was not associated with any therapeutic effect of IFN. Multivariate analysis indicated that HCV-RNA load was a significant risk factor, but among the patients with low viremia (HCV-RNA <100 MU/L), leptin level was an independent risk factor for IFN resistance. Namely, a high level of serum leptin attenuated the effect of IFN on both male and female patients with low viremia.. High serum leptin level is a negative predictor of response to antiviral treatment in chronic hepatitis C with low viremia.

Topics: Adult; Aged; Body Mass Index; Female; Hepatitis C, Chronic; Humans; Interferons; Leptin; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Viremia

Genotype-3 of hepatitis C virus (HCV) has been associated with serum lipid changes (reversible with sustained viral response) and liver steatosis.. To characterize the relationships among hepatic steatosis, cholesterol and sustained viral response in these patients.. Patients (n = 215) with chronic hepatitis C (157 with genotype-1 of HCV) had age, body mass index, gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage (METAVIR and Scheuer), degree of liver steatosis, sustained viral response, insulinaemia, leptinaemia, beta-hydroxybutyrate and glycerol measured, and were compared with 32 hepatitis B virus (HBV)-infected subjects.. Genotype-3 of HCV patients had age-adjusted hypocholesterolaemia and more frequent hepatic steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype-3 of HCV and sustained viral response, serum cholesterol increased from 138 (95% CI: 120-151) to 180 mg/dL (95% CI: 171-199) 12 months after treatment conclusion (P < 0.0001). By contrast, cholesterol values were unchanged in genotype-3 of HCV non-responders and in patients with genotype-1 of HCV regardless of response. Rising cholesterol in sustained viral response did not parallel the changes in beta-hydroxybutyrate.. Besides causing hepatic steatosis, genotype-3 specifically decreases serum cholesterol. This interference with the metabolic lipid pathway is related to viral load, is reversed with sustained viral response, and seems unrelated to mitochondrial dysfunction.

Topics: C-Peptide; Cholesterol; Dyslipidemias; Fatty Liver; Female; Genotype; Hepatitis C, Chronic; Humans; Leptin; Male; Middle Aged

To study the serum leptin level and insulin resistance on sustained virological response (SVR) in patients with chronic hepatitis C and to evaluate whether serum leptin level and insulin resistance are independent risk factors.. Forty chronic hepatitis C patients were treated with interferon (alpha-2a) 5 MU and ribavirin 1.0 g for 24 weeks. The fasting serum leptin, insulin, glucose, HCV RNA load, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index (BMI) were calculated. Statistical methods used were univariate analyses and multivariable regression analyses.. Of the 40 patients, 23 patients (57.5%) had a sustained virological response and 17 patients (42.5%) had a non-sustained virological response. Patients with a sustained virological response had lower serum leptin, HOMA-IR and BMI. Their SVR was associated with age, HCV RNA loads, serum leptin level, and insulin resistance, when analyzed with univariate analyses. SVR was not associated with sex, ALT, or AST. With multivariable regression analyses, serum leptin level and insulin resistance were found to be independent prediction factors for SVR in chronic hepatitis C patients with antivirus treatment.. Serum leptin level and insulin resistance were associated with SVR in chronic hepatitis C patients; they were independent prediction factors for SVR.

Topics: Adult; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged

Topics: Adult; Female; Hepatitis C, Chronic; Humans; Leptin; Lipoproteins; Liver Function Tests; Male; Middle Aged

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.. 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.. 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.. HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.

Topics: Adult; Aged; Asian People; Body Mass Index; Energy Metabolism; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Leptin; Liver; Male; Middle Aged

Recent attention has focused on the liver profibrogenic role of leptin in animal models. The purpose of this study was to evaluate the role of leptin and TNF-alpha in the severity of liver fibrosis in patients with chronic hepatitis C (CHC). We used a radioimmunoassay to determine serum leptin concentrations in 77 consecutive patients with CHC and 22 healthy controls. Leptin was correlated with liver histological (METAVIR) and metabolic indices. Sixty five patients had none to moderate liver fibrosis (F0-F2) and twelve severe fibrosis (F3-F4). Steatosis was observed in all but 27 patients. Leptin was significantly increased in patients compared with controls and was significantly more elevated in females both in patients and controls. The age, age at infection, prothrombin index, body mass index (BMI), triglycerides, glycaemia, ferritin, leptin and TNF-alpha, were associated with severe fibrosis. Steatosis was significantly more pronounced in patients with severe than those without or moderate fibrosis (P = 0.04). Only leptin was significantly and independently associated with severe fibrosis (OR = 1.2, CI 95%: 1.1-1.4, P = 0.03). Leptin was significantly associated with BMI (r = 0.64, P < 0.001) and glycaemia (r = 0.43, P < 0.001). Significant correlations were found between steatosis and BMI (r = 0.30, P < 0.01) and glycaemia (r = 0.30, P < 0.01). In patients with CHC and higher BMI and glycaemia levels, the severity of liver fibrosis is associated with serum leptin. TNF-alpha is a putative candidate involved in the mechanism.

Topics: Adolescent; Adult; Case-Control Studies; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Leptin; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Severity of Illness Index; Tumor Necrosis Factor-alpha

Topics: Fatigue; Female; Hepatitis C, Chronic; Humans; Leptin; Male; Sex Factors

Topics: Body Mass Index; Clinical Trials as Topic; Fats; Fatty Liver; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Leptin; Liver; Liver Cirrhosis; Male; Sex Factors

Hepatic steatosis (HS) has been related to obesity and fibrosis in chronic hepatitis C (CHC). The aim of this study was to determine the role of leptin system in HS development.. Patients (n = 131) with biopsy-proven CHC, positive HCV RNA, and raised ALT were enrolled. Body mass index, percentage of body fat by skin fold measurement, and bioelectrical impedance analysis was calculated and serum leptin concentration measured. Intrahepatic HCV RNA, HS, necroinflammatory activity, and fibrosis were determined in liver biopsy tissue.. HS was present in 63 patients (48.1%). Steatosis was evident in 32 of 91 patients (35.2%) infected with genotype 1 and in 22 of 27 patients (81.5%) with genotype 3a (p < 0.001). In patients infected by genotype 3a, HS correlated significantly with intrahepatic HCV RNA load (r = 0.78; p < 0.001). However, in genotype 1, HS was associated with host factors such as leptin, body mass index, percentage of body fat, and visceral obesity. Multivariate analysis showed genotype (OR = 11.54, 95% CI = 1.13-117.14, p = 0.038), leptin levels (OR = 1.09, 95% CI = 1.03-1.17, p = 0.008) and fibrosis (OR = 9.86, 95% CI = 2.11-5.86, p = 0.03) as independent variables of HS development.. Hepatic steatosis was related to genotype, fibrosis degree, and serum leptin levels. Genotype 3 seems to have a viral specific steatogenic effect. Leptin seems to be a link between obesity and steatosis development in CHC genotype 1-infected patients.

Topics: Adult; Alcohol Drinking; Body Mass Index; Clinical Trials as Topic; Fatty Liver; Female; Fibrosis; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Leptin; Liver Cirrhosis; Liver Function Tests; Male; Multivariate Analysis; Polymerase Chain Reaction; Regression Analysis; RNA, Viral; Viral Load

Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression.. Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin.. Patients with viral genotype 3 had more severe steatosis (P=0.0001) and developed stages 1 and 2 fibrosis at a younger age (P<0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P=0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P=0.046) but not inflammation (P=0.83). There was no association between serum leptin levels and stage of fibrosis.. Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype.

Topics: Adult; Body Mass Index; Fatty Liver; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Insulin; Leptin; Liver Cirrhosis; Male; Middle Aged; Obesity

The aim of this study was to examine the possible relationship between the plasma levels of leptin and tumor necrosis factor (TNF)-alpha and the stage of hepatic fibrosis in a cohort of patients with chronic hepatitis C. Leptin and TNF levels were measured by RIA in 135 patients and in 75 age- and sex-matched controls. Liver disease was evaluated by the stage of fibrosis and the extent of inflammatory infiltrate in the liver biopsy. Leptin levels correlated with BMI values in healthy controls and in patients with chronic hepatitis C (men, r = 0.61, P = 0.0001; women, r = 0.68, P = 0.003). Leptin levels increased as hepatic fibrosis stage progressed both in male and in female patients (P < 0.001); also, TNF levels were higher in patients with an advanced stage of fibrosis (P = 0.006). In these patients, levels of leptin increased according to the progression of the stage of fibrosis; these data suggest that leptin may play a role in the regulation of hepatic fibrosis.

Topics: Adult; Aged; Disease Progression; Female; Hepatitis C, Chronic; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged

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

Topics: Fasting; Glucose; Hepatitis C, Chronic; Homeostasis; Humans; Insulin; Leptin; Reference Values

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

Topics: Diabetes Mellitus, Type 2; Hepatitis C, Chronic; Humans; Insulin; Insulin Resistance; Leptin; Risk Factors

In 18 patients with chronic hepatitis C we evaluated leptin (with IRMA method) and HGF and neopterin (with ELISA method) serum concentrations. Concentrations of leptin, HGF and neopterin were higher than in the control group. Leptin serum concentrations correlated with liver biopsy inflammatory grading, but higher HGF concentrations were connected with fibrosis staging. Neopterin correlated with both parameters and GGTP activity.. increased neopterin concentrations could inform about liver inflammation activity; leptin and HGF serum concentrations could reflect the liver damage intensity.

Topics: Adult; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Hepatitis C, Chronic; Hepatocyte Growth Factor; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged; Neopterin

Serum levels of leptin, the adipocyte-derived hormone regulating food intake and energy expenditure in mammals, have been found to be increased in cirrhotic patients. The aim of the present study was to investigate leptin serum level in relation to anthropometric features and liver function in patients with viral chronic hepatitis or liver cirrhosis.. Serum leptin levels were determined by radioimmunoassay in 30 male and 10 female patients with chronic hepatitis, in 42 male and 10 female patients with liver cirrhosis, and in four respective control groups. Liver function was evaluated by the monoethylglycinexylidide formation test. Body mass index and body fat mass were estimated by weight, height and skinfold thickness measurements.. Compared with controls, absolute serum leptin levels were significantly (p<0.01) lower in chronic hepatitis patients and similar in cirrhotic patients. Leptin serum levels were significantly (p<0.05) higher in cirrhotic than in chronic hepatitis patients. When expressed in relation to body fat mass, the above differences persisted; however, cirrhotic females showed significantly (p<0.05) higher serum leptin values than controls. Serum leptin values correlated negatively (p<0.01) with monoethylglycinexylidide serum values in all groups of patients.. In patients with chronic viral liver disease, serum leptin levels tend to increase as liver function worsens. This may reflect a decline in the ability to downregulate energy expenditure as an adaptation to anorexia and/or to defective substrate utilisation due to liver disease and may negatively influence body weight homeostasis in these patients.

Topics: Adipose Tissue; Adult; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Leptin; Lidocaine; Liver Cirrhosis; Male; Middle Aged; Organ Size; Reference Values

The presence of steatosis is a common histological finding in patients with chronic hepatitis C (CHC). The causes of the severity of this condition are not yet clear, although both metabolic and viral factors supposedly are involved. In this study our aim was to examine the possible influence that leptin levels, hepatitis C virus (HCV) RNA levels, and hepatitis G virus (HGV) infection have on the severity of steatosis and on the presence and degree of fibrosis in patients with CHC.. One hundred eighty-two CHC patients with histological findings of steatosis were chosen from among a cohort of patients referred to our center for staging of liver disease. Among them 48 CHC patients were accurately selected so as to rule out possible confounding factors for the presence of steatosis (diabetes mellitus, hyperlipemia, obesity, alcohol). Leptin levels, HCV RNA levels, and HCV genotype, and the presence of HGV RNA were assessed in these patients and related to histological findings.. We found that leptin levels in CHC patients were similar to those in healthy subjects. No relationship was found between leptin levels and severity of steatosis. HCV RNA levels, HCV genotype, and the presence of HGV infection were no different among CHC patients with various degrees of steatosis. Leptin was not related to different degrees of fibrosis, whereas higher viral load was the only parameter associated to higher fibrosis scores.. These findings suggest that the degree of steatosis in patients with CHC does not seem to depend on serum leptin levels or on viral factors, at least as far as HCV viremia and genotype and HGV infection are concerned. The severity of fibrosis does not seem to be influenced by leptin levels, whereas HCV viral load does seem to play some role.

Topics: Adult; Case-Control Studies; Fatty Liver; Female; Flaviviridae; Hepacivirus; Hepatitis C, Chronic; Hepatitis, Viral, Human; Humans; Leptin; Liver; Liver Cirrhosis; Male; Middle Aged; RNA, Viral; Severity of Illness Index; Viral Load