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.     

Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases

BACKGROUND AND AIM: Thrombocytopenia typically worsens with the progression of liver disease and can become a major clinical complication. Several mechanisms that contribute to thrombocytopenia have been proposed, including hypersplenism accompanied by increased platelet sequestration, platelet destruction mediated by platelet-associated immunoglobulins (PAIgG), and diminished platelet production stimulated by thrombopoietin (TPO). The purpose of the present study was to evaluate the role of each of these mechanisms in patients with liver disease-associated thrombocytopenia. METHODS: Twenty-nine patients with liver cirrhosis (LC), 20 of whom were hepatitis C virus (HCV)-seropositive, 29 chronic hepatitis (CH) patients, 24 of whom were HCV-seropositive, and 16 control patients without liver or hematopoetic disease were enrolled in this study. Serum TPO levels, PAIgG, and liver-spleen volumes were determined and correlation analyses were performed. RESULTS: No differences in serum TPO levels were observed among the three groups. The PAIgG levels were significantly elevated in CH and LC patients (mean +/- SD: 56.5 +/- 42.3 and 144.6 +/- 113.6 ng/107 cells, respectively) compared with the controls (18.9 +/- 2.5 ng/107 cells, P < 0.001 for both). Spleen volume was significantly higher only in LC (428 +/- 239) compared with CH (141 +/- 55) and control (104 +/- 50 cm3) (P < 0.001), while liver volume was not significantly different between the three groups. Correlation analyses demonstrated a significant negative correlation between platelet count with PAIgG (r = - 0.517, P < 0.001) and spleen volume (r = - 0.531, P < 0.001), and no relationship between platelet count and serum TPO level (r = 0.076). CONCLUSIONS: Serum TPO level may not be directly associated with thrombocytopenia in patients with chronic hepatitis and liver cirrhosis. In contrast, spleen volume and PAIgG are associated with thrombocytopenia in such patients, suggesting that hypersplenism and immune-mediated processes are predominant thrombocytopenic mechanisms.     

The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients

BACKGROUND: Our aim was to study liver disorders in asymptomatic patients with slightly to moderately increased liver transaminase values in a population living in an area with a low prevalence of viral and hereditary liver diseases. METHODS: One hundred and fifty consecutive patients with slightly to moderately increased liver transaminases for at least 6 months without symptoms or signs of liver disease were included. Median (range) was 0.75 microkat/l (0.24-2.9) for aspartate aminotransferase (ASAT) and 1.18 microkat/l (0.28-4.5) for alanine aminotransferase (ALAT). A percutaneous liver biopsy was performed, and blood was sampled for a detailed biochemical and serologic profile. RESULTS: Chronic viral hepatitis C was found in 15.3% of the patients, autoimmune hepatitis in 1.3%, primary biliary cirrhosis in 1.3%, and heterozygotic alpha-1-antitrypsin deficiency in 0.7%. Presumed alcoholic liver disease was diagnosed in 8%, and non-alcoholic steatohepatitis in 2%. Chronic hepatitis with no obvious etiology was diagnosed in 24%, of whom 39% had interface hepatitis (piecemeal activity). Seventy-one per cent of these 39% had measurable levels of autoantibodies, but IgG levels within normal limits prevented the 'clinical' diagnosis of autoimmune hepatitis. Liver steatosis was the diagnosis in 40%. Most were overweight and had increased serum triglyceride levels. However, in 13.3% the fatty infiltration was considered 'essential', as both body mass index (BMI) and triglyceride levels were normal. Other diagnoses were liver fibrosis with no obvious inflammatory activity (3.3%), cirrhosis of unknown etiology (0.7%), and for the remaining (3.3%) patients histopathologic findings were considered 'normal'. Cirrhosis was found in five biopsy specimens: hepatitis C (n = 2), autoimmune hepatitis (n = 1), primary biliary cirrhosis (n = 1), and cryptogenic cirrhosis (n = 1). No concomitant disease was of importance for the diagnosis and/or histopathologic findings. No obvious drug-related increased liver test results were found with any single drug. However, patients with chronic hepatitis of unknown etiology, especially with interface hepatitis, significantly more often than the rest of the population were receiving drug treatment. CONCLUSION: Most transaminitis patients had steatosis, and some had defined diseases including chronic hepatitis C. Chronic hepatitis of unknown etiology was found in a substantial proportion (24%) of a population living in an area with a low burden of hepatic viruses and genetic disorders.     

Serum tenascin levels in chronic liver disease

To evaluate the diagnostic significance of tenascin, the extracellular matrix glycoprotein in chronic liver disease, serum tenascin levels were measured by a newly developed ELISA in 21 patients with chronic persistent hepatitis, in 55 with chronic active hepatitis, in 59 with liver cirrhosis, in 31 with hepatocellular carcinoma, in 26 with acute hepatitis and in 66 healthy subjects. The serum tenascin level was significantly elevated in the patients with chronic active hepatitis, liver cirrhosis, hepatocellular carcinoma, and acute hepatitis when compared with the healthy subjects (P<0.001). The serum tenascin level also increased with increasing severity of chronic liver diseases. A significant correlation was observed between the serum tenascin levels and serum levels of various extracellular matrix proteins such as type III procollagen N-aminoterminal peptide (PIIIP), laminin and the 7S domain of type IV collagen (P<0.001). A strong positive correlation was observed between the serum tenascin levels and histologic findings, particularly in the degree of hepatic fibrosis. This is the first report documenting serum tenascin level increases in patients with various chronic liver diseases. The measurement of the serum tenascin levels may provide additional information relevant to the study of connective tissue.     

Thrombocytopenia associated with liver cirrhosis and hepatitis C viral infection: role of thrombopoietin

BACKGROUND/AIMS: Thrombocytopenia in chronic liver diseases has traditionally been considered a consequence of platelet pooling and destruction in spleen. We tried to evaluate the influence of thrombopoietin, the physiological regulator of thrombopoiesis, on the origin of this thrombocytopenia. METHODOLOGY: We determined serum thrombopoietin levels by ELISA in thrombocytopenic patients with liver cirrhosis (n = 32) and with chronic hepatitis C viral infection (n = 23). A group of 43 healthy subjects was used as a control. RESULTS: Liver cirrhosis patients presented slightly, but not significantly, lower serum thrombopoietin levels (104 +/- 56 pg/mL) than controls (121 +/- 58 pg/mL) or patients infected with chronic hepatitis C virus (125 +/- 40 pg/mL). No correlations were found between serum thrombopoietin concentrations and liver tests or hematological parameters. CONCLUSIONS: We conclude that low thrombopoietin production may play a role, along with hypersplenism, in the development of thrombocytopenia in patients with liver cirrhosis. Normal thrombopoietin levels exclude a defect in thrombopoietin production as a possible etiology for the thrombocytopenia in patients with chronic hepatitis C viral infection. However, a direct viral megakaryocyte infection or an immune mechanism could explain this thrombocytopenia, according to the thrombopoietin levels detected.     

Thrombopoietin level in patients with chronic liver diseases

Thrombocytopenia and oxidative stress are the most frequent problems in patients with chronic liver diseases as viral cirrhosis and schistosomiasis. So, this study aimed to evaluate the role of thrombopoietin (TPO) on the occurrence of thrombocytopenia and in differentiation between these diseases. It also aimed to investigate the relation between TPO, oxidative stress and antioxidant status in these two types of chronic liver disease. So, We measured serum TPO level, lipid peroxide (MDA) and serum total antioxidant activity (TAO) in 40 patients with cirrhosis caused by hepatitis C virus and 37 patients with schistosomiasis from The Specialized Medical Hospital, Mansoura University. Results: Both serum TPO level and serum TAO activity were significantly lower (p < 0.05) in thrombocytopenic patients with viral cirrhosis when compared to both non thrombocytopenic and control groups. In contrast, TPO level was within the normal range in the patients with scistosomiasis either thrombocytopenic or not. while serum TAO activity was significantly lower (p < 0.05) in both thrombocytopenic and non thrombocytopenic patients with schistosomiasis in comparison to control subjects with no significant difference between these two subgroups. Serum MDA concentration was increased significantly (p < 0.05) in all diseased groups when compared to controls with significant increase in thrombocytopenic patients as compared to non thrombocytopenic. Conclusion: TPO hypoproduction played a role in the pathogenesis and treatment of viral cirrhosis associated with thrombocytopenia. Also, total antioxidant activity and MDA are useful markers for monitoring patients with these chronic liver diseases.     

Plasma thrombopoietin levels in liver cirrhosis and kidney failure

BACKGROUND: Recently, c-Mpl ligand (thrombopoietin, TPO) has been cloned by several groups and found to be a primary regulator of thrombopoiesis. Its mRNA expression has been detected in several organs including kidneys, bone marrow stroma cells, muscles, and is very strongly expressed in the liver. OBJECTIVE: To clarify thrombopoiesis and the regulation of TPO in severe liver and renal failure. DESIGN: We analysed plasma TPO levels in patients with biopsy verified liver cirrhosis (n = 18; mean platelet count 115 +/- 54 x 109 L-1), in patients on chronic haemodialysis as a result of end-stage renal failure (n = 20; mean platelet count 295 +/- 94 x 109 L-1), and in healthy individuals (n = 20; mean platelet count 250 +/- 40 x 109 L-1). Plasma was prepared from EDTA-anticoagulated whole blood and a commercially available ELISA kit was used for the analysis. RESULTS: The mean plasma TPO concentration amongst the normal individuals was 50 +/- 14 pg mL-1. In the patients with liver cirrhosis and in patients on haemodialysis the mean TPO levels were 62 +/- 19 pg mL-1 and 46 +/- 17 pg mL-1, respectively. The mean plasma TPO concentration for the cirrhotic patients was significantly higher than the mean recorded for the healthy volunteers (P = 0.031), whereas no statistically significant differences in plasma TPO were seen between the group of end-stage renal failure and normals. CONCLUSION: Our results suggest that TPO production is maintained in liver cirrhosis and in renal failure, and that the thrombocytopenia in liver cirrhosis is not due to an impaired TPO production.     

Upregulation of lymphotoxin beta expression in liver progenitor (oval) cells in chronic hepatitis C

BACKGROUND: Bipotent liver progenitor (oval) cells with the ability to differentiate into hepatocytes and biliary epithelium have recently been identified in human subjects with hepatitis C. Animal studies suggest that members of the tumour necrosis factor family, including lymphotoxin beta (LT-beta), regulate oval cell proliferation in liver disease, but its role in human liver disease is unclear. AIMS: This study seeks to establish a role for LT-beta in hepatitis C related liver injury and to provide evidence that its increased expression is related to the presence of oval cells. METHODS: Liver biopsy specimens were obtained from patients with chronic hepatitis C virus (HCV) infection (n=20). Control liver samples (n=5) were obtained from liver resection or transplant surgery. LT-beta expression in liver biopsy specimens was studied using quantitative real time polymerase chain reaction and immunohistochemistry. RESULTS: LT-beta mRNA levels were similar in control and HCV liver in the absence of fibrosis. In subjects with portal fibrosis, LT-beta mRNA levels were elevated 2.2-fold over control liver levels (p=0.04). In subjects with bridging fibrosis, LT-beta mRNA levels increased 4.4-fold over control liver levels (p=0.02). LT-beta mRNA levels in subjects with established cirrhosis were increased 3.3-fold compared with controls and 2.6-fold compared with mild liver damage (p=0.02). Immunohistochemical analysis established that LT-beta was expressed by oval cells, inflammatory cells, and small portal hepatocytes. CONCLUSIONS: In chronic HCV infection, LT-beta expression is observed in multiple hepatic cell types, including oval cells. LT-beta expression is significantly increased when fibrosis or cirrhosis is present, suggesting a role for LT-beta in the pathogenesis of chronic hepatitis C and a possible role in oval cell mediated liver regeneration.     

Hepatic production of insulin-like growth factors in normal and diseased liver

BACKGROUND/AIMS: IGF-I levels are reduced in cirrhotic patients. However, it is not known whether this decreased level is the result of reduced hepatic production or modified bioavailability secondary to decreased binding proteins. We determined the hepatic production of IGF-I and IGF-II and their receptors in normal and diseased liver. METHODOLOGY: Twenty-five patients included, 11 controls with normal liver and 14 with either chronic hepatitis or cirrhosis. mRNA for IGF-1, IGF-II and their receptors were measured. Immunohistochemical staining was performed to localize the IGF-producing cells. RESULTS: In 11 normal livers, the IGF-I mRNA levels were 4.95 +/- 1.8; in the 14 diseased livers, the levels were 1.22 +/- 0.69 (p < 0.001). IGF-II mRNA levels were 3.78 +/- 1.45 for the control and 5.11 +/- 2.15 in the diseased livers (NS). IGF-I receptor levels were 1.15 +/- 0.83 in the normal and 0.31 +/- 0.22 in the liver disease group (p < 0.05). There was no statistical difference between the two groups for IGF-II receptor. CONCLUSIONS: Patients with chronic liver disease have a significant reduction in their hepatic production of IGF-I, whereas IGF-II tends to be elevated. Treatment with recombinant IGF-I in patients with metabolic or endocrine complications of cirrhosis might prove useful.     

Hepatic prolyl hydroxylase activity in human liver disease

The activity of prolyl hydroxylase was measured in liver tissue obtained from a small series of patients with a variety of liver disease. Enzyme levels were marginally elevated in patients with fatty liver and viral hepatitis, conditions not normally associated with progressive fibrosis. In some patients with alcoholic hepatitis and in all patients with cirrhosis and chronic active hepatitis, there was a marked increase in enzyme activity. Patients with conditions characterised by high liver prolyl hydroxylase levels showed histological evidence of extensive hepatic fibrosis and also significant increases in the serum values of glutamate dehydrogenase and gamma-glutamyl-transpeptidase. Prolyl hydroxylase activity was not detected in serum.     

Evaluation of plasma thrombomodulin (TM) levels in patients with liver disease]

Plasma TM levels in patients with various liver diseases were determined by using EIA. In normal subject (n = 58), it's concentration was 15.9 +/- 3.5 ng/ml (mean +/- SD). In liver diseases, the level increased: Acute hepatitis (n = 16), 23.0 +/- 6.5, chronic active hepatitis (n = 21) 22.2 +/- 6.6, compensated liver cirrhosis (n = 20) 27.8 +/- 10.1, decompensated liver cirrhosis (n = 14) 47.6 +/- 17.5, compensated liver cirrhosis with hepatocellular carcinoma (n = 7) 26.3 +/- 7.9, decompensated liver cirrhosis with hepatocellular carcinoma (n = 4) 46.0 +/- 11.8, and fulminant hepatitis (n = 9) 42.0 +/- 20.4. The percentages of abnormal values higher than 22.9 ng/ml, which is mean + 2SD in control subject was 38-100% in liver diseases, especially 100% in patients with liver cirrhosis or with fulminant hepatitis. There was little correlation between plasma TM levels and conventional liver function tests in various liver diseases. Immunohistochemical study of liver tissue showed that an increase of plasma TM level was partially caused by damage and regeneration of endothelial cell. Based on these results the measurement of plasma TM concentration could be an useful marker for detection of hepatic failure.     

Serum hyaluronan--a non-invasive test for diagnosing liver cirrhosis

INTRODUCTION: Hyaluronan is a glucosaminoglycan synthesized by the mesenchymal cells and degraded by hepatic sinusoidal endothelial cells by a specific receptor-mediated process. Elevated levels are associated with the sinusoidal capillarization that is seen in cirrhosis. METHODOLOGY: Serum hyaluronan was measured, using a radiometric assay (Pharmacia, Sweden) in 221 patients with biopsy-proven chronic liver disease of a variety of aetiologies (alcohol n = 70, autoimmune chronic active hepatitis n = 23, primary biliary cirrhosis n = 17, hepatitis C n = 69, cryptogenic n = 15, various n = 27). All patients were fasted, and their liver function tests, full blood count, prothrombin time and Child-Pugh score were assessed at the time of the liver biopsy. RESULTS: Hyaluronan levels (microg/l) were significantly higher in patients with liver cirrhosis (cirrhosis n = 127, mean 440, 95% CI 367-515) (P < 0.0001) compared with hepatic fibrosis (n = 23, mean 144, 95% CI 69-190), chronic hepatitis (n = 60, mean 63, 95% CI 37-91) and fatty liver (n = 11, mean 107, 95% CI 37-177). Within the cirrhotic population, there was no significant difference in hyaluronan levels between different aetiologies, but hyaluronan level increased proportionally to the severity of cirrhosis. Overall, a hyaluronan level > 100 microg/l had a 78% specificity and 83% sensitivity for diagnosing cirrhosis, while the specificity was increased to 96% for all patients with hyaluronan levels > 300 microg/l. The highest specificity and sensitivity were seen at a cut-off value of 100 microg/l in patients with alcohol-associated liver disease (89%, 87%) and hepatitis C (93%, 72%) respectively. Within patient cohorts, there was a significant correlation (P < 0.01) between hyaluronan and albumin, platelet count and bilirubin, but not with alanine aminotransferase. CONCLUSION: Measurement of fasted serum hyaluronan reliably differentiated cirrhotic from non-cirrhotic liver disease and can be regarded as a useful test in the diagnosis of liver cirrhosis, particularly when a liver biopsy is contraindicated.     

Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis,and its relationship with circulating thrombocyte counts

BACKGROUND/AIMS: Thrombocytopenia in chronic liver diseases may be related to deficient production of thrombopoietin. The aim of this study was to measure serum thrombopoietin levels and to examine the relationship between serum thrombopoietin concentration, circulating platelet counts and clinical stage of the disease in patients with chronic hepatitis and liver cirrhosis. METHODOLOGY: The study included 18 patients with chronic hepatitis, 48 with liver cirrhosis and 27 healthy volunteers. Serum thrombopoietin levels were measured by enzyme-linked immunosorbent assay. Additionally, serum albumin levels, prothrombin time, circulating platelet counts and spleen volume index were determined. RESULTS: Mean serum thrombopoietin level (100.96 +/- 41.67 pg/mL) in the chronic hepatitis group was similar to that of the healthy group (97.60 +/- 43.99 pg/mL), however serum thrombopoietin levels in patients with liver cirrhosis (69.60 +/- 30.23 pg/mL) were lower than patients with chronic hepatitis and controls (p < 0.05 for both). In patients with liver cirrhosis, serum thrombopoietin levels were found to be decreased as the disease progressed (80.99 +/- 24.85 pg/mL in patients at Child-Pugh stage A, 67.92 +/- 39.37 in patients at stage B and 57.62 +/- 21.09 pg/mL in patients at stage C). Cirrhotic patients had increased prothrombin time (17.12 +/- 3.52 sec) and spleen volume index (94.38 +/- 26.48 cm2), and decreased serum albumin level (3.11 +/- 0.56 g/dL) and platelet counts (102,368 +/- 30,653/mm3) when compared to both chronic hepatitis and control groups. Thrombocytopenia was found in 31 (65%) of the patients with liver cirrhosis. In patients with liver cirrhosis, while there was a positive correlation between serum thrombopoietin and albumin levels (r = 0.36, p = 0.004), no correlation was found between platelet counts and serum thrombopoietin level, and spleen volume index. CONCLUSIONS: The findings reveal that serum thrombopoietin levels are normal in patients with chronic hepatitis, but in patients with liver cirrhosis, serum thrombopoietin levels decrease, as degree of cirrhosis progresses. The impaired production of thrombopoietin may contribute to the development of thrombocytopenia in advanced stage of liver disease.     

The relationship between hepatic immunoglobulin production and CD154 expression in chronic liver diseases.

BACKGROUND: CD40-CD154 is a receptor-ligand pair that provides key communication signals between cells of the adaptive immune system in states of inflammation and autoimmunity. The CD40 receptor is expressed constitutively on B lymphocytes, for which it provides important signals regulating clonal expansion and antibody production. CD154 is a member of the tumor necrosis factor superfamily, which is primarily expressed by activated T cells. METHODS: Because many chronic liver diseases are characterized by lymphocytic infiltration of the liver and several have increased immunoglobulin (Ig) production, the role of CD40-CD154 in hepatic Ig production was investigated in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune hepatitis (AIH), hepatitis C, hepatitis B, alcoholic and non-alcoholic steatohepatitis, as well as normal controls. RESULTS: Soluble CD154 levels in the serum were found to be no different in chronic liver diseases vs normal controls. Likewise, CD154 mRNA levels in peripheral blood mononuclear cells did not differ. However, mRNA for CD154 was significantly increased in the liver of individuals with PBC and AIH as compared with the other groups. The quantity of CD154 mRNA in the liver correlated positively with the quantity of mRNA for secretory Ig. CONCLUSION: These findings suggest that CD40-CD154 signals may be involved in Ig production within the liver of autoimmune liver diseases.     

Significance of the iron and copper content of the liver for the differential diagnosis of chronic liver diseases

Liver iron and copper concentrations were estimated in 395 patients undergoing hepatological examination. Relations to clinical, morphological and laboratory data were evaluated. Liver iron concentrations were not significantly different in chronic hepatitis of viral, toxic or immunological origin. Liver iron levels exceeding 100 mg/100 g dry liver tissue (normal range up to 300 mg/100 g) were only found in idiopathic hemochromatosis (n = 8), in a patient with prophyria cutanea tarda and in a multiple transfused patient who suffered from aplastic anemia. Liver copper content was significantly increased in primary biliary cirrhosis compared to chronic hepatitis of other origin. Apart from untreated Wilson's disease (n = 3) copper levels higher than 25 mg/100 g dry liver tissue (normal range up to 6 mg/100 g) were measured in chronic active hepatitis B (n = 2), primary biliary cirrhosis (n = 9) and in chronic hepatitis of uncertain origin (n = 3). Therefore excess accumulation of copper in the liver was typical of Wilson's disease but less diagnostic than severely elevated liver iron stores of idiopathic hemochromatosis.     

Value of serum immunoglobulins in the diagnosis of liver disease

Serum immunoglobulins were determined in 145 consecutive patients with biopsy-proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p less than 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p less than 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.     

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.     

Serum xanthine oxidase in human liver disease

OBJECTIVES: High concentrations of serum xanthine oxidase (XO) have been reported during human liver disease and hepatocyte injury in experimental settings. However, it is unclear whether this elevation reflects hepatocyte necrosis or has a different meaning. METHODS: The serum level of XO in 64 patients with chronic liver disease (17 patients with cirrhosis, 30 with chronic hepatitis, and 17 with cholestatic disorders) and in 12 control subjects was determined by a competitive ELISA. Conventional serum markers of liver damage were assessed in all patients, and grading and staging were scored in the chronic hepatitis group according to Knodell. RESULTS: The XO serum levels were significantly higher in the patients than in the controls. The differences were also significant when controls were compared to patients with chronic hepatitis and cholestatic disorders separately, but not when compared to the cirrhosis group. Patients with cholestatic disorders had XO values higher than those of patients with cirrhosis or chronic hepatitis. XO levels did not correlate with stage and grade in chronic hepatitis group. We found a weak but significant positive correlation in patients between XO serum level and gamma-glutamyl transpeptidase (r = 0.37). This correlation was stronger when chronic hepatitis (r = 0.42) and, especially cholestatic disorders (r = 0.71), were separately tested, but was absent in the cirrhosis group. The XO values positively correlated with alkaline phosphatase in patients with cholestatic disorders. A level of serum XO >32 microg/ml specifically identified cholestatic disorders in our study population. CONCLUSIONS: A marked elevation of serum XO in patients with chronic liver disease seems to reflect the presence of cholestasis. No correlation between XO levels and histological or serum evidence of hepatocyte necrosis was found in these patients.