Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.     

Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis

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

Serum Leptin Levels in Patients with Liver Cirrhosis and Chronic Viral Hepatitis

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

慢性肝病血清瘦素水平测定

为了解慢性肝炎、脂肪肝、肝硬化患者血清瘦素水平情况，选择慢性肝炎17例，脂肪肝、肝硬化、正常对照各21例，分别测量受试者的身高、体重，计算体重指数(BMI)、体脂肪含量(％Fat)，血清瘦素水平采用酶联免疫吸附试验(BLISA)的方法测定，并进行结果分析。结果显示：肝炎组、脂肪肝组瘦素水平明显高于对照组；肝硬化组与对照组无差异，血清瘦素水平与肝功能分级无关；丙型肝炎病毒所致的肝病血清瘦素水平与对照组相比差异不显著。上述说明瘦素与多数慢性肝病有关。     

Increased serum leptin concentrations correlate with soluble tumour necrosis factor receptor levels in patients with cirrhosis

OBJECTIVE: Several reports have documented the involvement of hyerleptinaemia in malnutrition associated with liver cirrhosis. However, the mechanisms of elevated leptin levels remains unclear. Serum concentrations of tumour necrosis factor-alpha (TNF-alpha), and two soluble TNF receptors (sTNF-RI and sTNF-RII) are increased in patients with liver cirrhosis. In rodents, administration of TNF-alpha has been shown to stimulate plasma leptin concentration, suggesting that a cytokine-leptin link may mediate anorexia and weight loss during chronic inflammation. In this study, we investigate the potential interaction of the TNF-alpha system with leptin in the development of malnutrition in liver cirrhosis. STUDY DESIGN: A total of 26 male patients with liver cirrhosis and 25 healthy people were recruited at an outpatient clinic at the Veterans General Hospital in Taiwan. Serum biochemistry and anthropometric measurement by bioelectrical impedance analysis were used to assess nutrition status, and immunoassay was used to determine serum leptin, TNF-alpha sTNF-RI and sTNF-RII concentrations. RESULTS: In cirrhotic patients, the body fat mass (FM) and serum albumin levels were both lower than control subjects [15.8 (13.2-19.5) kg vs. 18.9 (16.2-20.1) kg; 35 (33-41) g/l vs. 43 (41-45) g/l, respectively; P < 0.05]. Serum TNF-alpha sTNF-RI and sTNF-RII were significantly elevated in cirrhotic patients compared to healthy controls [9.8 (7.2-13.5) ng/l vs. 4.3 (3.4-7.3) ng/l; 1682.1 (1344.8-2179.4) ng/l vs. 1319.6 (1037.7-1632.1) ng/l; 4462.2 (3748.5-5159.4) ng/l vs. 3559.8 (2506.9-3988.9 ng/l, respectively; P < 0.01] and correlated with disease severity (graded by Pugh-Child's scores). An inverse correlation was observed between circulating sTNF-RI and sTNF-RII to serum albumin levels (r =-0.42, r = -0.398; P < 0.05). The serum leptin levels in cirrhotic patients were significantly higher [6.0 (3.6-7.7) (g/l vs. 3.4 (2.9-4.3) (g/l; P < 0.01) and correlated with body FM (r = 0.52; P < 0.01]. Using a multiple linear regression analysis with leptin as dependent variable and FM and TNF-alpha, sTNF-R as independent variables, FM and serum sTNF-RI concentrations were found to predict independently the leptin levels in cirrhotic patients. CONCLUSION: Our study demonstrated that serum levels of TNF-alpha, sTNF-RI, sTNF-RII and leptin were all elevated in cirrhotic patients. The severity of liver cirrhosis was an important factor for the activation of TNF-alpha system. The activated TNF-alpha system conjointly with hyperleptinaemia might mediate malnutrition in patients with liver cirrhosis.     

Elevated bound leptin correlates with energy expenditure in cirrhotics

BACKGROUND & AIMS: Leptin, found to be elevated in patients with liver cirrhosis, may contribute to the inadequate energy expenditure and malnutrition associated with a negative prognosis for these patients. Our aim was to characterize leptin components and their relationships to body composition, resting energy expenditure (REE), and substrate use in patients with posthepatic liver cirrhosis. METHODS: Using specific radioimmunoassays, we measured free leptin and bound leptin in 27 cirrhotics and 27 matched control subjects. In the cirrhotic group, body composition and REE were determined. RESULTS: Free leptin was not different in cirrhotics and control subjects and was related to body mass index (controls: r = 0.34, P < 0.05; cirrhotics: r = 0.55, P < 0.005) and to fat mass (cirrhotics: r = 0.76, P < 0.0001). Bound leptin was significantly higher in cirrhotic subjects than in controls (P < 0.001) and was related to REE x fat-free mass(-1) (r = 0.57, P < 0.005) or to the difference between measured and estimated REE (r = 0.55, P < 0.005). CONCLUSIONS: Free leptin reflects fat mass in controls and cirrhotics. Increased serum leptin in cirrhotics is a result of increased bound leptin serum concentrations, which are positively related to energy expenditure. Moreover, bound leptin may be a useful marker for inadequate energy expenditure in patients with liver cirrhosis.     

男性乙型肝炎肝硬化患者血清瘦素及血脂水平的研究

目的检测男性乙型肝炎肝硬化患者血清瘦素及血脂水平，探讨其异常变化的临床意义。方法男性乙型肝炎肝硬化患者64例，男性健康受试者28名，用ELISA法检测血清瘦素水平，用全自动生化分析仪检测肝功能和血脂。对血清瘦素、血脂与肝功能的关系进行分析。结果各组乙型肝炎肝硬化Child-Pugh分级患者与对照组比，血清瘦素水平无显著性差异（P〉0．05）；与正常对照组比，乙型肝炎肝硬化患者血CHO和LDL水平显著降低（P〈0．01），按Child分级由A到C级各组CHO和LDL水平逐渐降低，差异有显著性（P〈0．01）。无腹水肝硬化患者血清瘦素水平与BMI及Fat％均呈显著正相关。结论血清瘦素水平不能作为评价男性乙型肝炎肝硬化患者病情严重程度的指标，血清胆固醇、低密度脂蛋白是肝功能减退的指标。瘦素可能参与了男性乙型肝炎肝硬化患者的营养不良。     

Serum leptin levels in patients with nonalcoholic chronic liver disease

BACKGROUND/AIMS: The elevated serum leptin level of patients with alcoholic cirrhosis has been reported, however, the precise mechanism is still unknown. Leptin expression and protein synthesis have also been detected in activated hepatic stellate cells in cell cultures, which play a major role in hepatic fibrosis. We evaluated the serum leptin levels of patients with nonalcoholic liver diseases including cirrhosis and chronic hepatitis. We also investigated the hepatic clearance of leptin by determining the serum leptin level in blood samples obtained from the portal and hepatic veins. METHODOLOGY: The serum leptin level of 44 patients with nonalcoholic chronic liver disease (male/female = 21/23, cirrhosis/chronic hepatitis = 30/14) and 40 control subjects (male/female = 20/20) was determined in blood samples obtained from the antecubital vein by enzyme-linked immunosorbent assay. We also assessed the relationship between the leptin level and various biochemical tests of liver function. Additionally, we determined the leptin levels in the portal and the hepatic venous blood (nonalcoholic cirrhosis = 10, nonhepatic disease = 4). RESULTS: There were positive correlations between the serum leptin level and body mass index among males and among females in the liver disease group and in the control group. However, the serum leptin level of the liver disease group and control group did not differ significantly. Among the 44 liver disease patients, only the serum cholesterol level was significantly correlated with the serum leptin level after adjusting for sex and body mass index by multiple regression analysis. Furthermore, the leptin level in hepatic venous blood was significantly lower than that in portal venous blood. However, the ratio of [leptin level in hepatic venous blood]/[leptin level in portal venous blood] in the cirrhosis group, and that in the nonhepatic disease group, did not significantly differ. CONCLUSIONS: The serum leptin level of patients with nonalcoholic liver diseases is not elevated. On the other hand, the serum leptin level of patients with alcoholic cirrhosis has been reported to be elevated. The difference in the serum leptin level of patients with nonalcoholic liver disease and that of patients with alcoholic cirrhosis may be due to a difference in factors such as the levels of cytokines or sex steroids, and/or nutrition. Furthermore, it is likely that leptin is cleared in part by the portosystemic circulation through the liver.     

Leptin levels in nonalcoholic steatohepatitis and chronic hepatitis C.

BACKGROUND/AIMS: Leptin is a peptide which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. Steatosis is a common finding in chronic hepatitis C, and both viral and metabolic factors have been suggested to explain the presence of this histological characteristic. In order to study leptin in chronic liver disease characterized by the presence of steatosis, we evaluated its serum levels in patients with nonalcoholic steatohepatitis (NASH), in chronic hepatitis C (CHC) patients with no histological findings of steatosis, and CHC patients with steatosis but no risk factors for its development. METHODOLOGY: We studied 6 male patients with NASH whose diagnosis was made on the basis of histological findings and clinical criteria. From among a cohort of 170 CHC patients we put together 2 groups of 6 male patients each (with or without steatosis at liver biopsy examination), who had no risk factors for NASH. Male patients were chosen in order to avoid gender influence on leptin levels. Further criteria for admission were similar impairment of liver metabolic function as assessed by the monoethylglycinexylidide (MEGX) test and, in patients with CHC, similar body mass index (BMI) and histological staging. Moreover, we evaluated leptin/BMI ratio, in order to rule out BMI influence on leptin levels. Leptin levels were assessed by means of radioimmunoassay. RESULTS: We found that BMI was higher in NASH compared to CHC (27.2 +/- 2.9 vs. 23.9 +/- 1.8; p = 0.01). Analysis of serum leptin levels showed an increasing trend starting from patients with CHC without steatosis (3.2 +/- 0.4 ng/ml), through CHC patients with steatosis (4.2 +/- 0.7 ng/ml) up to patients with NASH (5.7 +/- 2 ng/ml), although the differences observed were not statistically significant. Moreover, the ratio of leptin to BMI also followed the same trend showing increasing values (CHC without steatosis = 0.04 +/- 0.02; CHC patients with steatosis = 0.17 +/- 0.03; NASH = 0.203 +/- 0.07). Leptin levels and BMI showed a significant relationship (n = 18; r = 0.60; p < 0.01). CONCLUSIONS: The increasing trend observed in leptin serum levels among the different groups of patients showed that in chronic liver disease characterized by the presence of steatosis, leptin signaling is preserved. Moreover, CHC factors different from the metabolic ones should be investigated in order to explain the presence of steatosis. Further studies on broader groups of patients are needed to verify these preliminary results.     

High Ascitic Fluid Leptin Levels in Patients with Decompensated Liver Cirrhosis and Sterile Ascites: Relationship with TNF-α Levels

Leptin is an adipocyte-derived hormone involved in the homeostasis of body composition. An imbalance in leptin regulation has been observed in patients with liver cirrhosis. We aimed to assess serum and ascitic leptin levels in a group of patients with decompensated liver cirrhosis and to evaluate the relationship of these levels with tumor necrosis factor alpha (TNF-alpha). We assessed both serum and ascitic fluid leptin levels in a series of 16 consecutive patients with liver cirrhosis. We calculated the body mass index (BMI) and assessed body fat (BF) of all patients by means of bioelectric impedence analysis. Leptin levels were analyzed in relationship to biochemical indexes, TNF-alpha levels, and body composition. None of the patients had spontaneous bacterial peritonitis. Both serum and ascites leptin levels were correlated with BMI and BF. On average, ascitic fluid leptin levels (13.1 +/- 10.9 ng/ml) were twice as high as serum levels (7.0 +/- 6.4 ng/ml), and the ascitic fluid/serum ratio of leptin was > 1 in all patients. Serum and ascites leptin levels were positively correlated (rS = 0.675, P = 0.009), while no correlation was observed between leptin and TNF-alpha levels, both in serum and in ascites. Serum and ascites TNF-alpha were not correlated. The ascitic fluid leptin levels of cirrhotic patients with sterile ascites are on average two times higher than circulating levels of this hormone. Noteworthily, they correlate significantly with body composition. These findings seem to suggest that in patients with decompensated liver cirrhosis, intraabdominal production of leptin may contribute to the metabolic picture.     

Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity

AIM： To evaluate serum neopterin levels and their correlations with liver function tests and histological grade in children with hepatitis-B-related chronic liver disease. METHODS： The study population comprised 48 patients with chronic active hepatitis B, 32 patients with hepatitis-B-related active liver cirrhosis and 40 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay. RESULTS： The mean ＋ SD serum neopterin levels were 14.2 ± 5.6 nmol/L in patients with chronic hepatitis, 20.3 ± 7.9 nmol/L in patients with liver cirrhosis and 5.2 ± 1.4 nmol/L in control group. Serum neopterin levels were significantly higher in patients with chronic hepatitis （P = 0.005） and cirrhosis patients （P = 0.008）, than in control subjects. Cirrhotic patients had significantly higher serum neopterin levels than patients with chronic hepatitis （P = 0.004）. There was a positive correlation between serum neopterin levels and alanine aminotransferase levels in patients with chronic hepatitis （r = 0.41, P = 0.004） and cirrhotic patients （r = 0.39, P = 0.005）. Positive correlations were detected between serum neopterin levels and inflammatory score in patients with chronic hepatitis （r = 0.51, P = 0.003） and cirrhotic patients （r = 0.49, P = 0.001）. CONCLUSION： Our results suggest that serum neopterin levels can be considered as a marker of inflammatory activity and severity of disease in children with hepatitis-B-related chronic liver disease.     

Serum leptin in patients with alcoholic liver disease

BACKGROUND: The mechanisms by which overweight makes the liver more susceptible to alcoholic liver injury remain to be determined. Therefore, we conducted the following studies to further elucidate the role of leptin in the pathogenesis of steatosis and cirrhosis caused by chronic alcohol consumption in human beings. METHODS: Two-hundred nine consecutive patients with alcoholic liver disease were studied. Serum leptin concentrations were measured by using radioimmunoassay, and the relationships between serum leptin level and liver lesions were studied. Statistical analysis used logistic regressions. RESULTS: When serum leptin, serum cholesterol, and body mass index (BMI) were considered together in the multiple logistic regression analysis, compared with patients with severe steatosis, serum leptin remains significantly lower in patients without steatosis (p<0.05) and in patients with mild or moderate steatosis (p<0.05). When age, serum leptin, serum cholesterol, and steatosis grade were considered together in the logistic regression analysis, serum leptin (p<0.01) and age (p<0.02) were positively and independently correlated with the presence of cirrhosis. After BMI introduction in the statistical model, serum leptin was no more correlated with the presence of cirrhosis. CONCLUSION: In patients with alcoholic liver disease, serum leptin is independently correlated with steatosis grade and might play an important role in severity of fibrosis as fatty liver is more vulnerable than normal liver to factors that lead to fibrosis.     

Serum hyaluronic acid concentrations in children with cirrhosis.

BACKGROUND: Liver disease is associated with increased levels of hyaluronic acid (HA). AIM: To evaluate serum HA concentrations in children with cirrhosis and its relation with liver function tests and Child-Pugh score. METHODS: Twenty-two children with biopsy-proven liver cirrhosis were studied. All were assessed for the presence of ascites or encephalopathy and liver function tests were performed. Patients were categorized according to Child-Pugh criteria. Serum HA was measured using microELISA (normal 0-100 ng/mL). Twenty-two children with chronic hepatitis B and no cirrhosis were studied as controls. RESULTS: Serum HA level in the cirrhotic children was 85.2 (72.8) ng/mL; levels were high (166.0 [46.3] ng/mL; range 115-246) in 8 (36.4%) patients. Three of 11 (27.2%) Child-Pugh class A patients, 3 of 8 (37.5%) class B patients, and 2 of 3 (66.7%) class C patients had elevated serum HA values (p=ns). Serum HA levels correlated with direct bilirubin level. The control group had lower levels (4.8 [2.3] ng/mL; p< 0.05), which were in the normal range. CONCLUSION: Serum HA level may be useful as a diagnostic tool in children with cirrhosis.     

13CO2 excretion in breath of normal subjects and cirrhotic patients after 13C-aminopyrine oral load. Comparison with MEGX test in functional differentiation between chronic hepatitis and liver cirrhosis

BACKGROUND/AIMS: Liver function can be evaluated using 13C breath tests that explore liver Cytochrome P450 activity. Aminopyrine is one of the first compounds used in liver function testing. Lidocaine metabolism to monoethylglycinexylidide is also a valid tool to assess liver function. Although liver Cytochrome P450 metabolizes both compounds, lidocaine metabolism is flow-dependent while aminopyrine metabolism does not depend on liver blood flow. METHODOLOGY: The 1st part of the study evaluated the appearance and disappearance rate of 13CO2 in the breath of both normal subjects and in cirrhotic patients, so as to establish optimal sampling times and to evaluate the amount of time needed before performing a subsequent breath test. The 2nd part of the study compared the aminopyrine breath test with the monoethylglycinexylidide test in patients with chronic hepatitis or cirrhosis. RESULTS: Complete 13CO2 disappearance was recorded 24 hours after the test in normal subjects, while it took 3 days to disappear from the breath of cirrhotic patients. Breath sampling at 60, 120 and 180 min were equally valid in differentiating chronic hepatitis from cirrhosis. The aminopyrine breath test and monoethylglycinexylidide test showed a good yet not close correlation. CONCLUSIONS: This study showed that in cirrhotic patients a 13C breath test can be performed 3 days after the previous one. In chronic hepatitis and cirrhotic patients, the aminopyrine breath test and the monoethylglycinexylidide test evaluated similar, but not identical, hepatic subfunctions, suggesting that multiple 13C breath test using different substrates could explore liver function better.     

肝硬化患者血清瘦素与胰岛素抵抗的关系

目的 探讨肝硬化患者血清瘦素水平的变化情况和影响因素,及其与胰岛素抵抗的关系。方法 选择肾功能正常的43例肝硬化患者和30例与其在性别、年龄和体重指数（BMI）相匹配的时照者,应用放免法测定血清瘦素。同时测定肝肾功能、血糖、血脂、胰岛素和C-肽等指标,并测量其身高、体重,计算BMI。结果 肝硬化患者血清瘦素水平同比对照组相比差异不显著;肝硬化组与对照组血清瘦素水平女性均高于男性;肝硬化患者血清瘦素水平与BMI、胰岛素和C-肽呈正相关,与胰岛素抵抗指数呈负相关;不同肝功能分级的肝硬化患者间血清瘦素水平差异不显著。结论 肝硬化患者血清瘦素水平存在性别差异。瘦素水平不能作为评价肝硬化严重程度的指标。瘦素与肝硬化患者的胰岛素抵抗相关。     

Adenosine deaminase isoenzymes and neopterin in liver cirrhosis

The aim of this study was to define the pattern of neopterin and ADA isoenzymes in liver cirrhosis. A total of 117 patients with liver cirrhosis were included. Serum levels of ADA were assayed in the presence and absence of a specific inhibitor for ADA1. Serum neopterin was measured using a competitive enzyme-linked immunosorbent assay. The grade of liver insufficiency was assessed according to the Child-Pugh classification and the monoethylglycinexylidide test. Serum ADA, ADA1, ADA2 and neopterin were higher in cirrhotic patients than in control subjects. A stepwise increase in serum ADA level was observed with increasing severity of liver cirrhosis. The probability of ADA2 being greater than the mean was approximately 2.5 times higher (2.48, CI 95%: 1.36-4.52) in patients with liver cirrhosis due to hepatitis C virus (HCV) infection than in those patients with cirrhosis of a different etiology. No correlation was found between ADA2 and neopterin. Our data show that liver insufficiency and HCV infection increase the serum levels of ADA and its major isoenzyme ADA2. Furthermore, ADA isoenzyme determination adds no value to total ADA value. The absence of a correlation between ADA2 and neopterin suggests that different physiologic processes are involved in their increase.     

Hepatitis C and the leptin system: bound leptin levels are elevated in patients with hepatitis C and decrease during antiviral therapy

BACKGROUND: Serum leptin levels are elevated in alcoholic liver cirrhosis and thus might be involved in the anorexia and hypermetabolism often seen in those patients. We hypothesized that the leptin system is modulated in patients with hepatitis C and might be affected by antiviral therapy. The aim of this study was to investigate the different leptin components in serum of patients with hepatitis C before, during and after interferon alpha and ribavirin therapy and in controls. METHODS: 25 patients (11 female, 14 male) with chronic hepatitis C were compared with body mass index, gender and age-matched controls (n = 25). Patients were treated with interferon alpha alone (3 MU tiw) or in combination with ribavirin for 6-12 months. Free leptin and bound leptin levels were measured using specific radioimmunoassays before interferon therapy, at 12 weeks of therapy and after 3 months of follow-up. RESULTS: Free leptin levels were higher in female than in male subjects, both for patients (P < 0.01) and controls (P < 0.05). Bound leptin levels were elevated in both female (P < 0.05) and male (P < 0.001) patients compared to controls. No alteration of free leptin levels was found during therapy, whereas bound leptin levels decreased after 3 months of therapy (P < 0.005) and re-increased to the baseline levels 3 months after therapy was stopped. Responder but not non-responder had decreased bound leptin levels (P < 0.01) comparing pre- and posttreatment levels. However, no significant correlations were determined between any of the leptin components to virus load, ALT, TNF alpha receptor levels (sTNFR-75, sTNFR-55) and histopathology at any time point. CONCLUSION: Since no correlation was found between the different leptin components and any of the inflammatory markers, the decrease in bound leptin levels during antiviral therapy suggests either a direct interferon-dependent effect on the leptin system or an alteration of other leptin secretagogues.     

Increased serum soluble tumor necrosis factor receptor levels are associated with insulin resistance in liver cirrhosis

Insulin resistance is present in nearly all patients with liver cirrhosis, but its etiology remains unclear. Recent studies have shown that tumor necrosis factor-alpha (TNF-alpha) system is involved in the insulin resistance of human obesity. Serum concentrations of TNF-alpha, and 2 soluble TNF receptors (sTNF-RI and sTNF-RII) are increased in cirrhotic patients. This study explored whether TNF-alpha system activity was associated with insulin resistance in liver cirrhosis. A total of 26 male nondiabetic patients with liver cirrhosis (mean age, 59 +/- 3 years; body mass index, 23.7 +/- 0.4 kg/m2) and 25 male control subjects (age, 65 +/- 2 years; body mass index, 24.4 +/- 0.5 kg/m2) were studied. Serum insulin, c-peptide, TNF-alpha, sTNF-RI, and sTNF-RII concentrations were determined by immunoassay. The insulin resistance was estimated by homeostasis assessment model (HOMA IR). In cirrhotic patients, serum levels of TNF-alpha, sTNF-RI, and sTNF-RII were all higher than those in the controls, and correlated with disease severity. Also, the serum c-peptide, insulin concentrations, and the HOMA IR were higher in liver cirrhosis with comparable blood glucose to control subjects, indicating a degree of insulin insensitivity. In the whole population, there was a moderate, but statistically significant, correlation between serum sTNF-RI or sTNF-RII, and HOMA IR. Also, body mass index was associated with HOMA IR, but not related to serum TNF-alpha, and sTNF-Rs levels. In multiple regression analysis, both sTNF-RII and body mass index jointly contributed to 30% variance of HOMA IR. Our study demonstrated that elevated sTNF-RII levels were associated with insulin resistance in liver cirrhosis. The data indicated that TNF-alpha system might play a role in modulating insulin action in patients with liver cirrhosis.     

Serum dolichols in chronic cholestatic liver diseases

BACKGROUND/AIMS: Dolichols are long-chain polyisoprenoid alcohols. It has been suggested that they modify membrane fluidity, stability and permeability. Some lysosomal diseases are associated with elevated serum dolichol levels. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol, however, is not known. METHODS: We therefore studied the effect of early or intermediate primary biliary cirrhosis, primary sclerosing cholangitis and alcoholic liver cirrhosis on serum dolichol concentration. Furthermore, serum dolichol content was measured in patients with end-stage primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis, waiting to be transplanted. RESULTS: As compared to age-adjusted controls, serum dolichol was significantly increased in early and intermediate primary biliary cirrhosis (451+/-56 ng/ml vs. 225+/-13 ng/ml, p<0.0001) and primary sclerosing cholangitis (315+/-16 ng/ml vs. 224+/-7 ng/ml, p<0.0001). However, in alcoholic liver cirrhosis serum dolichol was unaffected. Serum dolichol content was also significantly elevated in patients with end-stage primary biliary cirrhosis (844+/-210 ng/ml vs. 225+/-13, p<0.001) and chronic active hepatitis (594+/-198 vs. 224+/-7 ng/ml, p<0.02). Furthermore, in patients with liver diseases serum dolichol concentration correlated positively with serum high density lipoprotein (HDL)-cholesterol (r = +0.50, p<0.0001). CONCLUSIONS: Serum dolichol levels are elevated in all stages of chronic cholestatic liver diseases but not in alcoholic liver cirrhosis. Impaired biliary excretion of dolichols appears to be the primary explanation for this finding.     

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease

OBJECTIVE: To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. METHODS: One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P<0.05). RESULTS: Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection. CONCLUSION: Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.