leptin and Hepatitis-B--Chronic

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

To evaluate the effect of Zhenggan Tang decoction on serum levels of leptin, adiponectin and insulin resistance on liver cirrhosis induced by chronic hepatitis B.. Sixty-six patients were recruited and randomly assigned either to a control group or to an intervention group, with 35 cases in the treatment and 31 in the control group respectively. Patients in the control group received inosine tablets and vitamin C treatment while patients in the treatment group were given Zhenggan Tang decoction additionally. After 3 months of treatment, the serum levels of leptin and adiponectin were detected and the index of insulin resistance calculated.. There were no significant difference between the serum levels of leptin, adiponectin and the index of insulin resistance seen in the control group before and after the treatment. Serum levels of leptin and adiponectin and the index of insulin resistance in treatment group were reduced significantly after the treatment (P < 0.05). There were significant difference in the serum levels of leptin and adiponectin between treat group and control group (P < 0.05).. Zhenggan Tang decoction seemed to have reduced the serum levels of leptin, adiponectin and the index of insulin resistance among cirrhotic patients that induced by chronic hepatitis B.

Topics: Adiponectin; Drugs, Chinese Herbal; Hepatitis B, Chronic; Humans; Insulin Resistance; Leptin; Liver Cirrhosis; Treatment Outcome

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

The relationship between hepatitis B virus (HBV) infection, leptin and insulin resistance remains unclear. We hypothesised links between serum leptin and insulin resistance in non-diabetic patients with chronic viral hepatitis B infection and their relation to liver fibrosis.. We recruited 190 untreated patients with chronic HBV infection and 72 healthy controls. Serum leptin, fasting glucose, insulin, liver function tests (LFTs), C-peptide and Homeostasis model assessment-IR (HOMA-IR) were measured/calculated by ELISA and standard techniques.. Serum leptin, C-peptide (both P < 0.001), HOMA-IR (P = 0.021) and several LFTs were increased in patients with chronic HBV-infection. In multivariate regression analysis, both HOMA-IR (P = 0.003) and leptin (P = 0.002) were significant independent predictors of HBV infection. There were significant positive correlations (P < 0.01) between leptin and HOMA-IR (r = 0.81), between serum leptin and METAVIR activity (r = 0.95), and between HOMA-IR and BMI (r = 0.75), fasting glucose (r = 0.005), and fasting insulin (r = 0.81). Several LFTs, glucose and insulin correlated modestly (r = 0.61-0.69, P < 0.05) with leptin.. Serum leptin may be related to the rate of fibrosis progression in nondiabetic patients with chronic HBV infection. Follow-up by serial measurement of serum leptin and HOMA-IR in non diabetic HBV-infected patients may be used as a non-invasive marker of early liver fibrosis.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Fasting; Female; Hepatitis B virus; Hepatitis B, Chronic; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged

Adipocytokines play an important role in lipid metabolism and liver disease progression. However, the interactions between hepatitis B virus (HBV) infection and adipocytokines remain largely unknown.. To investigate the association of HBV infection with adipocytokines in HBV-infected and noninfected subjects. In addition, the impact of adipocytokines on serum HBV DNA, HBsAg levels and liver fibrosis stage was also examined.. A case-control analysis of patients with and without chronic HBV infection was performed. The HBV group consisted of 187 patients with chronic HBV infection, and the control group consisted of 184 age-, gender- and body mass index-matched subjects without HBV infection. Fasting blood glucose, lipid profiles, adiponectin, leptin and visfatin levels were compared between the two groups. APRI and FIB-4 were calculated to estimate the severity of liver fibrosis.. Most of the enrolled subjects had lower ALT levels [228 (57.7%) ALT < ULN] and milder hepatic fibrosis [381 (96.5%) APRI < 0.7; 307 (77.7%) FIB4 < 1.45]. The HBV group had significantly higher serum adiponectin and visfatin but lower leptin levels than the control group. This difference remained significant after adjustment for age, sex, BMI and ALT levels (p < 0.05). Serum adiponectin, leptin and visfatin levels were significantly associated with serum HBsAg and HBV DNA levels (p < 0.05). In addition, a higher serum adiponectin level was associated with advanced liver fibrosis in elder male HBeAg-negative patients.. Patients with chronic HBV infection have significantly higher serum adiponectin and visfatin but lower leptin levels than healthy controls. Serum adipocytokine levels independently correlate with HBV viremia, HBsAg levels and liver fibrosis stages.

Topics: Adiponectin; Adult; Age Factors; Alanine Transaminase; Aspartate Aminotransferases; Case-Control Studies; Cohort Studies; DNA, Viral; Female; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Leptin; Liver Cirrhosis; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Platelet Count; Severity of Illness Index; Sex Factors

Obesity is considered a risk factor for hepatocellular carcinoma (HCC). The relationship between adipocytokine and HCC in hepatitis B virus (HBV) carriers remains unclear. We prospectively investigated the association of adiponectin, leptin, and visfatin levels with HCC.. We conducted a nested case-control study in a community-based cohort with 187 incident HCC and 374 HCC-free HBV carriers. Unconditional logistic regression was conducted to estimate the ORs and 95% confidence intervals (CI).. Adiponectin, but not leptin and visfatin, levels were associated with an increased risk of HCC after adjustment for other metabolic factors and HBV-related factors. The risk was increased [OR = 0.51; 95% CI, 0.12-2.11; OR = 4.88 (1.46-16.3); OR = 3.79 (1.10-13.0); OR = 4.13 (1.13-15.1) with each additional quintiles, respectively] with a significant dose-response trend (P(trend) = 0.003). HCC risk associated with higher adiponectin level was higher in HBV carriers with ultrasonographic fatty liver, genotype C infection, higher viral load, and with elevated alanine aminotransferase. Longitudinally, participants with higher adiponectin were less likely to achieve surface antigen of hepatitis B virus (HBsAg) seroclearance and more likely to have persistently higher HBV DNA. Eventually, they were more likely to develop liver cirrhosis [OR = 1.65 (0.62-4.39); OR = 3.85 (1.47-10.1); OR = 2.56 (0.96-6.84); OR = 3.76 (1.33-10.7) for the second, third, fourth, and fifth quintiles, respectively; P(trend) = 0.017] before HCC.. Elevated adiponectin levels were independently associated with an increased risk of HCC.. Adiponectin may play different roles in the virus-induced and metabolic-related liver diseases, but the underlying mechanism remains unknown.

Topics: Adipokines; Adiponectin; Adult; Aged; Carcinoma, Hepatocellular; Case-Control Studies; Cytokines; Female; Hepatitis B, Chronic; Humans; Incidence; Leptin; Liver Neoplasms; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Risk Factors

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

Chronic hepatitis B patients with diabetes and metabolic syndrome are at increased risk of cirrhosis and hepatocellular carcinoma, but the underlying mechanism is unclear. Our objective was to test whether dysregulation of adipokines contributes to liver injury. We also studied whether viral factors affected adipokines, insulin resistance, and hepatic steatosis.. A prospective cohort of 266 chronic hepatitis B patients undergoing liver biopsy was studied. Fasting blood was taken for the analysis of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), adiponectin, leptin, and resistin. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Factors associated with significant necroinflammation and cirrhosis were identified.. Histological activity index was correlated with serum TNF-alpha (R=0.40, P<0.0001) and IL-6 (R=0.32, P<0.0001) but not with adiponectin, leptin, or resistin. By multivariate analysis, TNF-alpha was associated with significant necroinflammation after adjusting for age and viral factors (odds ratio (OR) 1.041, 95% confidence interval (CI) 1.002-1.082, P=0.04). Serum adiponectin had positive correlation with hepatitis B virus DNA (R=0.17, P=0.007) and was decreased in patients with insulin resistance and hepatic steatosis. On the other hand, viral load, hepatitis B e-antigen status, and genotypes had no association with insulin resistance, hepatic steatosis, and the levels of TNF-alpha and IL-6. A total of 68 (25.6%) patients had cirrhosis. HOMA-IR, but not adipokine dysregulation, was independently associated with cirrhosis (OR 1.09, 95% CI 1.02-1.15, P=0.006).. TNF-alpha and/or IL-6 contribute to hepatic necroinflammation in chronic hepatitis B patients. Adiponectin protects against insulin resistance and hepatic steatosis but does not affect liver injury. Adipokines and viral factors contribute to liver injury independently.

Topics: Adipokines; Adiponectin; Adult; Biopsy; China; Fatty Liver; Female; Hepatitis B, Chronic; Humans; Insulin Resistance; Interleukin-6; Leptin; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Prospective Studies; Resistin; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

The purpose of this study was to determine the leptin levels in children with chronic hepatitis B virus (HBV) infection, and to evaluate the effect of serum leptin levels on the end of therapy response (ETR). It is known that leptin stimulates T-cell immunity and so T-cell mediated immune response is critical in the outcome of chronic HBV infection.. Leptin levels in children with chronic HBV infection were investigated and its effects on the ETR in 24 children who were treated with interferon-alpha and lamivudine combination therapy were evaluated.. The mean leptin level of the patients was higher than that of healthy children (P = 0.034). Of the patients, seven (29.2%) had ETR. The mean hepatic activity index and portal inflammation score were higher, the HBV DNA was lower, and the leptin level was similar in children with ETR when compared to others (P = 0.017, P = 0.04, P = 0.007, P = 0.34, respectively). HBV DNA and the fibrosis score were positively correlated (P = 0.016).. Although the higher leptin value observed in children with ETR was not statistically significant, because of close interactions between leptin, cytokines and lymphocytes, it is thought that leptin should be investigated as a predictive factor of ETR in further studies.

Topics: Child; Female; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Leptin; Male; Treatment Outcome

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

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