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1.
BACKGROUND: Serum levels of soluble interleukin-2 receptor (sIL-2R) seem to serve as a marker for the activation of T lymphocytes. The aim of this study was to evaluate the clinical significance of such levels in patients with chronic hepatitis C (CHC) treated with interferon. METHODS: We measured serum levels of sIL-2R in 37 patients with CHC before and after treatment with recombinant interferon-alpha. Serum receptor levels were then compared with the response of the hepatitis C virus (HCV)-RNA level in serum after interferon. RESULTS: Receptor levels were significantly higher in the patients with chronic persistent hepatitis and chronic active hepatitis than in normal controls (p < 0.01). There was a weak correlation between serum sIL-2R and alanine aminotransferase (ALAT) levels (r = 0.14, p = 0.010). Patients were then classified into three groups on the basis of the effect of interferon treatment on HCV-RNA levels in serum: sustained response (SR; n = 21), non-sustained response (NSR; n = 14), and nonresponse (NR; n = 2). Before and during interferon treatment the serum sIL-2R level remained increased in the SR group and in the combined groups with NSR or NR. However, after interferon was withdrawn, the serum sIL-2R decreased in the SR group but remained significantly increased in the combined response group (p < 0.01-0.05). CONCLUSION: This finding seems to reflect the disappearance of HCV-RNA from the serum of the patients with an SR, and monitoring of sIL-2R levels may therefore be of value as an adjunct to the measurement of serum ALAT and HCV-RNA in evaluating the response to the interferon therapy for CHC.  相似文献   

2.
BACKGROUND/AIMS: Correlations between serum levels of soluble tumor necrosis factor receptors p55 (TNFsRp55) and Child Pugh index have previously been reported in alcoholic patients with cirrhosis. We have undertaken this study to improve understanding of the role of tumor necrosis factor soluble receptors (TNFsRs) in alcoholic liver disease. METHODS: One hundred and two patients with alcoholic liver disease of various severity (23 pure steatosis, 22 fibrosis, seven acute alcoholic hepatitis without cirrhosis, 12 cirrhosis without acute alcoholic hepatitis, 14 cirrhosis with mild acute alcoholic hepatitis and 24 cirrhosis with severe acute alcoholic hepatitis) were studied. Blood was collected on EDTA and plasma was tested for TNFsR concentrations using ELISA assays. RESULTS: Plasma levels of TNFsRp55 and p75 increased progressively with the severity of liver disease, reaching a maximum in cirrhotic patients with severe acute alcoholic hepatitis. Plasma levels of TNFsRp55 in patients with fibrosis and of TNFsRp75 in patients with acute alcoholic hepatitis without cirrhosis were already higher than in healthy controls. In cirrhotic patients with or without acute alcoholic hepatitis TNFsRp55 and p75 were significantly increased compared with controls. In cirrhotic patients, plasma levels of TNFsRp55 correlated positively with all parameters of liver injury, whereas the TNFsRp75/ TNFsRp55 ratio correlated negatively. In cirrhotic patients with severe acute alcoholic hepatitis, the TNFsRp75/TNFsRp55 ratio was significantly lower than in all other groups. In cirrhotic patients with severe acute alcoholic hepatitis treated by prednisolone, the decrease in TNFsRp55 plasma levels between day 1 and day 15 was significantly more important in patients still alive at 2 months than in patients who died within 2 months. CONCLUSIONS: These results show that the expression of TNF-soluble receptors (TNFsRs) participates in the early phases of the alcoholic liver disease and that the TNFsRp75/TNFsRp55 ratio and plasma levels of TNFsRp55 may help to determine the diagnosis and the prognosis of severe acute alcoholic hepatitis in cirrhotics.  相似文献   

3.
Assessment of immunity was performed in 150 patients with alcoholic liver disease (15 steatosis, 30 hepatitis and 105 cirrhosis: 34 in grade A, 34 in grade B and 37 in grade C, according to Child-Pugh classification). This assessment was based on the total lymphocyte count and a delayed hypersensitivity skin multiple test. Likewise, nutritional status of patients was studied using anthropometric and biochemical parameters (triceps skinfold thickness, arm muscle circumference and serum albumin). The association between alcoholic liver disease, malnutrition and immunity was analyzed. The results show that lymphopenia and disorders in cell-mediate immunity were more common in those patients with cirrhosis, increasing the number of anergic patients while the degree of hepatocellular insufficiency worsens (8.8% in grade A, 11.8% in grade B and 32.4% in grade C). Although there where significantly more alterations of delayed cutaneous hypersensitivity in cirrhotics with malnutrition (hypoergy: 55.2% and anergy: 37.9%) than in those well nourished (hypoergy: 23.7% and anergy: 10.5%, p < 0.01), lymphopenia didn't show differences between these groups. We think that immunity mus'nt be considered a parameter in nutritional assessment.  相似文献   

4.
5.
BACKGROUND: Cytokines and cytokine receptors are involved in the systemic and local inflammatory response in patients with urinary tract infections. METHODS: We examined urine and serum concentrations of soluble IL-6 receptor (sIL-6R), IL-10 and granulocyte colony-stimulating factor (G-CSF) in 29 women with acute pyelonephritis caused by Escherichia coli 2 weeks after the infection, during the subsequent episode of cystitis or asymptomatic bacteriuria and also later when the same patients were free from bacteriuria. Concentrations of sIL-6R, IL-10 and G-CSF were related to the expression of five virulence markers of E. coli and to glomerular filtration rate (GFR) after pyelonephritis. RESULTS: On admission because of acute pyelonephritis the serum concentration of sIL-6R was similar to that of 12 healthy controls. Two weeks after the infection when all patients had received antibiotic treatment, the serum concentration of sIL-6R was significantly higher compared to that on admission (p < 0.001) and also higher compared to healthy controls (p = 0.001). Patients with increased concentrations of sIL-6R in serum 2 weeks after infection had significantly lower GFR at follow-up (p < 0.05). Patients with acute pyelonephritis had higher concentrations of G-CSF and IL-10 in serum compared to healthy subjects (p < 0.001 and p = 0.06, respectively). G-CSF in serum was higher in patients infected by E. coli producing cytotoxic necrotizing factor (p < 0.05). Patients infected by strains producing hemolysin had lower concentrations of sIL-6R (p < 0.001). Patients with detectable levels of the anti-inflammatory cytokine IL-10 in serum had significantly higher concentrations of IL-6 and the soluble tumor necrosis factor receptors I and II in serum as compared to patients in whom IL-10 was not detectable (p < 0.001, p = 0.001 and p < 0.05, respectively. CONCLUSION: These investigations, together with our previous findings summarized in this paper, contribute to an increased understanding of the local and systemic inflammatory response arising in response to acute pyelonephritis.  相似文献   

6.
The levels of soluble interleukin-2 receptors (sIL-2R), beta-2 microglobulin (beta-2M), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured in the serum of 50 previously untreated patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) as well as in 25 age and sex-matched normal controls. Compared to normal controls, mean serum levels of sIL-2R and beta-2M were significantly increased in both NHL and CLL (p < 0.001) while the increase in ESR and CRP was less marked (p < 0.01 and p < 0.05, respectively). Comparison of these tumor markers with histologic grading showed statistically significant differences only for CRP between low, intermediate and high-grade lymphomas (p < 0.001 and p < 0.05). More advanced stages exhibited higher mean values of all serum markers than early stages (p < 0.001 for sIL-2R, beta-2M and ESR and p < 0.05 for CRP). An association with the presence of b-symptoms was observed only for sIL-2R (p < 0.05). In addition, sIL-2R as well as beta-2M were able to predict time to progression in patients with diffuse large-cell lymphomas. We conclude that of the four tumor markers tested sIL-2R and beta-2M more frequently showed increased serum levels and were associated with clinical stage and/or presence of b-symptoms. Both sIL-2R and beta-2M were also found to have prognostic significance for survival.  相似文献   

7.
OBJECTIVE: Lactoferrin, an immunoregulatory protein in mucosal secretions, is one of the target antigens to perinuclear antineutrophil cytoplasmic antibodies (P-ANCAs). Circulating lactoferrin is cleared in the liver, but little is known about the implication of lactoferrin in hepatic inflammation. To evaluate the implication of immunological response to lactoferrin, we examined antilactoferrin antibodies in autoimmune liver diseases. METHODS: Fourteen patients with primary biliary cirrhosis (PBC), 14 with autoimmune hepatitis (AIH), five with autoimmune cholangitis (AIC), six with chronic hepatitis C, and five with chronic hepatitis B were studied. We evaluated autoantibodies to lactoferrin in the sera of the patients by the Western Immunoblotting method. RESULTS: Sera of five of the 14 patients (35.7%) with PBC, four of the 14 patients (28.6%) with AIH, and five of the five patients (100%) with AIC contained autoantibodies to human lactoferrin, but none with hepatitis B or C had them. The higher prevalence of serum antibodies to human lactoferrin was shown to be higher in patients with AIC than with hepatitis B (p < 0.01), hepatitis C (p < 0.01), PBC (p < 0.05), and AIH (p < 0.05). CONCLUSION: Lactoferrin located in bile ducts and liver cells is one of the candidates of target antigens in autoimmune liver diseases, especially in AIC.  相似文献   

8.
BACKGROUND: Acquired deficiencies of certain complement proteins and impaired opsonisation activity have been implicated in the pathogenesis of the increased susceptibility to infections of patients with alcoholic cirrhosis. METHODS: Serum concentrations of C3 and C4, plasma concentrations of C3bc, C9, and the terminal C5b-9 complement complex (TCC), and haemolytic complement activity (classic and alternative pathway) of serum, and serum opsonic activity were determined in 46 patients with compensated alcoholic cirrhosis, 31 who were decompensated, and in 15 healthy subjects. After 19 months (median) the investigated variables were analysed for their use in prognosis of recurrent infections and survival. RESULTS: C3 and C4 concentrations and the haemolytic complement activity of the alternative pathway were decreased in decompensated cirrhotic patients compared with controls (p < 0.01). Univariate analysis (log rank test) showed that low concentrations (< or = lower quartile) of C3 (p < 0.001) and C3bc (p < 0.05), haemolytic complement activity of the alternative pathway (p < 0.01) and classic pathway (p < 0.05), and decompensated cirrhosis (p < 0.001) were associated with an increased risk of infection and increased mortality. Multivariate (Cox) analysis showed that low C3 concentrations and decompensation of cirrhosis were significant predictors of infections and mortality (p < 0.02). CONCLUSIONS: Low serum C3 concentrations and decreased haemolytic complement function predisposes to infection and increased mortality in patients with alcoholic cirrhosis.  相似文献   

9.
Body retinoids are stored in the lipid droplets of hepatic stellate (Ito) cells. In chronic liver disease, the stellate cells differentiate into myofibroblast-like cells, a process whereby they lose their retinoid-containing lipid droplets. We studied the relation between liver retinoid content, the number of lipid droplets per stellate cell, and the number of stellate cells per mm2 in human alcoholic liver disease. Semithin sections of liver biopsies from normal subjects and patients with early (steatosis, inflammation, and mild fibrosis) and late (cirrhosis and cirrhosis with acute alcoholic hepatitis) alcoholic liver disease were morphometrically evaluated. Liver retinoid content was determined by HPLC. In normal patients, liver retinoid content was 901 +/- 213 IU/g of liver (mean +/- SEM). There was a decrease in liver retinoid content in early alcoholic liver disease (409 +/- 50 IU/g) and a further reduction in cirrhosis (153 +/- 50 IU/g). In patients with acute alcoholic hepatitis, retinoid content was strikingly low (5.2 +/- 1.8 IU/g). There was a progressive decrease in the number of stellate cells per mm2 associated with progressive liver damage. We found a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups (overall correlation: 0.71). In normal subjects, the mean number of lipid droplets per stellate cell was 7.4 +/- 0.7. In patients with early alcoholic liver disease and in patients with alcoholic cirrhosis, this value was increased to 13.6 +/- 0.8 and 10.4 +/- 2.0, respectively. In patients with acute alcoholic hepatitis, only a few lipid droplets were present (4.2 +/- 0.5). There was a good correlation between liver retinoid content and mean number of lipid droplets in normal patients (r = 0.58). In alcoholic cirrhosis, however, correlation was poor (r = 0.34). In early alcoholic liver disease, the correlation was absent (r = 0.004). In conclusion, the major finding of our study is that the correlation between the mean number of lipid droplets per stellate cell and liver retinoid content varies according to the hepatic pathology considered. Marked lipid droplet accumulation occurs in stellate cells in early alcoholic liver disease and, to a lesser extent, in alcoholic cirrhosis, but there is no correlation between the mean number of lipid droplets per stellate cell and liver retinoid content. Therefore, not retinoids but probably lipids are responsible for the accumulation of lipid droplets. We also find that there is a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups. Finally, we confirm the decrease in hepatic retinoid content that occurs in alcoholic liver disease in humans, even at the early stages of the disease.  相似文献   

10.
BACKGROUND: Elevation of serum IgA is a characteristic feature of alcoholic liver disease. It has been proposed that this occurs partly as an antigenic response to gut-derived proteins or acetaldehyde-modified liver proteins, but the principal antigens responsible remain unknown. AIMS: The goal of this study was to determine if serum IgA antibodies were present against human gut luminal antigens or liver antigens in alcoholic liver disease. PATIENTS AND METHODS: Twenty-nine patients with alcoholic liver disease, 10 with primary biliary cirrhosis, 12 with "other" liver diseases, 8 alcoholics, and 20 healthy subjects were studied. Western blotting was used to examine the reactivity of sera from these groups against human small and large bowel aspirates and liver tissue from alcoholic liver disease patients. RESULTS: Serum IgA antibodies to a 140 kDa colonic luminal protein were found in 22 (76%) patients in the alcoholic liver disease group (p < 0.0001), and 7 (24%) patients had serum IgA antibodies to a 40 kDa colonic luminal protein (p = 0.04). These responses were confined to colonic aspirates and not observed in other disease groups, alcoholics or healthy subjects. There was no significant serum IgA response to human liver proteins in alcoholic liver disease. CONCLUSIONS: Serum IgA antibodies to a human 140 kDa colonic luminal protein are frequently found in alcoholic liver disease. This novel antigen may contribute to the increased levels of circulating IgA in alcoholic liver disease.  相似文献   

11.
Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 52 patients with multiple myeloma (MM) and 24 normal controls, using a commercially available immunoenzymatic assay kit. Patients were staged according to the Bataille et al. myeloma staging system based on the levels of patients' serum beta 2-microglobulin and C-reactive protein. Twenty-one patients were at stage A of disease, 19 at stage B and 12 at stage C at the time of serum collection for sIL-6R determination. Serum sIL-6R concentrations ranged from 15 to 176 ng/ml with a mean of 64.8 +/- 35.9 ng/ml and a median of 58 ng/ml in the entire group of patients studied. These values were significantly higher than those of 34.4 +/- 13.4 ng/ml found in the controls (P < or = 0.001). Patients of stage C had higher sIL-6R levels (94.8 + 41.2 ng/ml) than patients of stage B (67.7 +/- 31.0 ng/ml) (P < 0.01), and markedly higher than patients of stage A (45.0 +/- 23.1 ng/ml) (P < 0.001). Serum levels of sIL-6R in patients with stage A disease did not differ statistically from those of the controls. A linear positive correlation was observed between serum levels of the receptor and the stage of MM (r = 0.539, P < 0.001). These data strongly suggest that serum sIL-6R concentrations correlate with the stages of MM and may be used as an indicator of the activity of the disease.  相似文献   

12.
The diagnostic values of aminoterminal propeptide of type III procollagen and hyaluronan serum levels were compared as markers of liver fibrosis in two chronic liver diseases of different etiologies and pathophysiologies, namely primary biliary cirrhosis and chronic viral hepatitis C. The results were analysed in terms of the histological extent of fibrosis. Both serum procollagen-III peptide and hyaluronan were elevated in patients with primary biliary cirrhosis and chronic viral hepatitis C (p < 0.0001) relative to control values. A positive correlation was found between serum procollagen-III peptide levels and the histological grade of fibrosis in primary biliary cirrhosis (p < 0.001) but not in chronic viral hepatitis C, while a strong correlation was found between serum hyaluronan levels and histological fibrosis in both primary biliary cirrhosis and chronic viral hepatitis C (p < 0.001), independent of age. These results suggest that, in chronic liver diseases, serum hyaluronan levels could be an important indicator of the extent of fibrosis and should be assayed to monitor the response to treatment in controlled clinical trials.  相似文献   

13.
AIM: Heptral trial in alcoholic, drug and viral diseases of the liver. MATERIALS AND METHODS: 67 patients with chronic diffuse liver diseases were treated with heptral. The examination covered AlAt, AP, HHTP, bilirubin, cholesterol, CT of the liver, esophagogastroduodenoscopy. Heptral was given by two steps: 14 days of intravenous drops (800 mg/day) followed by 14 days of oral use (2 tablets, 400 mg each) before meal at 8 a.m. and 2 p.m. RESULTS: In alcoholic disease of the liver, heptral relieved depression, reduced AlAT, AP, HHTP, bilirubin, density of the liver. The addition of heptral to interferon-alpha-2 treatment of chronic hepatitis C corrected intrahepatic cholestasis. In drug-induced liver damage heptral promoted normalization of the hepatic tests, improved general condition of the patients. CONCLUSION: Heptral is effective in patients with alcoholic and drug liver lesions, chronic hepatitis C.  相似文献   

14.
Abnormalities of immune system compartments were determined in 12 patients with Huntington's disease (eight males, four females; age 42.4+/-11.7 years) and 11 controls (7 males, 4 females; age 47.0+/-12.0). All patients were free from infectious diseases. Serum concentrations of a panel of serum soluble markers of immune activation were investigated, namely neopterin, 55-kDa-type soluble tumor necrosis factor receptor (sTNF-R), interleukin-2-receptor (sIL-2R), kynurenine, tryptophan, immunoglobulins (Ig) A, M and G as well as routine laboratory tests. Compared to controls, we found significantly higher serum levels of IgA (p<0.01), sTNF-R, sIL-2R, neopterin, and complement component C3 (all p<0.05), and serum tryptophan was decreased (p<0.001). Higher concentrations of circulating immune complexes, cardiolipin antibodies, IgM, neopterin and lower tryptophan were associated with loss of cognitive function as assessed by the mini-mental-test. Five patients died within 1 year after measurements were performed. In these patients IgM, circulating immune complexes and neopterin concentrations were higher compared to survivors and serum tryptophan was lower. The data indicate an activation of various immune system compartments in Huntington's disease and that systemic immunological alterations might be important in the course of the disease.  相似文献   

15.
Acquired deficiencies of fibrinogen, antithrombin III and plasminogen are reported in liver disease, and it is known that their plasma levels fluctuate during the day. The aim of this study was to investigate the circadian rhythms of these three factors in chronic liver disease. Five groups of subjects were considered: (A) 15 healthy controls: (B) 15 patients with hepatic alcoholic steatosis; (C) 15 patients with chronic active hepatitis; (D) 15 patients with compensated cirrhosis of the liver, and (E) 15 patients with decompensated cirrhosis with ascites. The levels of fibrinogen, antithrombin III and plasminogen were determined in blood samples drawn in each subject during the span of a day every 3 h starting from midnight. The time-related values were analyzed using the 'population-mean cosinor' method. Groups A and B presented a significant (p < 0.05) circadian rhythm for each variable, group C a significant (p < 0.05) circadian rhythm for fibrinogen and antithrombin III and groups D and E no significant (p > 0.05) circadian rhythms. Statistically significant differences (p < 0.05) were demonstrated among the groups in the mean daily levels of the three variables by ANOVA, the concentrations decreasing with disease severity. These data confirm the existence of a significant diurnal periodicity in the circulating levels of fibrinogen, antithrombin III and plasminogen in controls and suggest that liver disease is associated with progressive circadian modifications in the temporal structure of fibrinogen, antithrombin III and plasminogen, related to the stage of the liver disease. The rhythm derangements may be considered markers of evolution in liver disease.  相似文献   

16.
The authors examined in detail the clinical and laboratory data and pathologic findings for 12 patients with alcoholic cardiomyopathy who were autopsied in the preceding ten years to determine the types of liver disease prevalent in this population. Neither alcoholic hepatitis nor cirrhosis was present in any patient, and most of the hepatic changes could be related to the effects of acute and chronic congestive heart failure. The major hepatic lesions included centrilobular congestion and/or ischemic necrosis, cardiac sclerosis (fibrosis about central veins and in perisinusoidal spaces), mild canalicular cholestasis, portal fibrosis, and nodular regenerative hyperplasia. This last finding may account for macroscopic nodularity resembling cirrhosis as well as portal hypertension in patients with alcoholic cardiomyopathy. Although alcoholic cardiomyopathy and alcoholic hepatitis or cirrhosis were mutually exclusive in the patients studied, the factors responsible for this are at present uncertain.  相似文献   

17.
OBJECTIVE: To determine 4 immunoglobulins and soluble interleukin-2 receptor (sIL-2R) in maternal and neonatal serum, in order to study the immunological functions in the neonates. METHODS: 80 cases were divided into three groups: (1) breast feeding group (30 cases), (2) formula feeding group (20 cases), and (3) mixed feeding group (30 cases). Maternal serum was collected prior to delivery and on the sixth day after delivery. Neonatal serum was collected on the third and sixth day after delivery. Umbilical blood at birth was obtained also. Secretory immunoglobulin A (SIgA), IgA, IgG, IgM and sIL-2R levels in the sera were determined by radioimmunoassay and enzyme-linked immunosorbent assay. RESULTS: The SIgA, IgA, IgG, IgM and sIL-2R levels in maternal serum were not significantly different among 3 groups, while neonatal serum SIgA, IgA, IgG, IgM and sIL-2R levels on the sixth day after delivery in the breast feeding group were significantly higher than those in the formula breeding group (P < 0.001, P < 0.001, P < 0.05, P < 0.05). CONCLUSION: Breast feeding may improve neonatal humoral and cellular immunity.  相似文献   

18.
It has been reported that serum hyaluronate [hyaluronic acid (HA)] concentrations are increased in liver diseases, especially in alcoholic liver disease (ALD). However, the characteristics of serum HA concentration in patients with ALD have not been studied. In this study, first, we measured serum HA concentrations in patients with different stages of both ALD and non-ALD to clarify the characteristics of serum HA concentration in patients with ALD. Second, we measured serum HA concentrations in patients with ALD sequentially after abstinence. We also measured serum HA concentrations in patients with chronic type C hepatitis before and after treatment with interferon. Finally, we analyzed the relationship between serum HA concentrations and the contents of type IV collagen and laminin in the livers of both ALD and non-ALD patients. Serum HA concentrations in liver disease were higher than the cut-off value, and increased significantly (p < 0.001) in parallel with the progression of hepatic fibrosis in both ALD and non-ALD patients. Serum HA concentrations in patients actively drinking with ALD were significantly higher (p < 0.001) than those in non-ALD. After 4 weeks of abstinence, these concentrations fell to the levels of non-ALD. Although serum ALT levels were decreased in 80% of patients treated with interferon, serum HA concentrations were not changed or increased. A significant correlation between serum HA concentrations and hepatic type IV collagen and laminin content was present in ALD, but not in non-ALD. These results clearly suggest that the increase of serum HA concentrations in ALD may be associated with not only hepatic fibrosis, but also alcohol drinking.  相似文献   

19.
OBJECTIVE: To investigate the possible relationship between serum levels of neopterin, soluble tumor necrosis factor-55 receptor (sTNF-55R), and soluble interleukin 2 receptor (sIL-2R) with disease activity in patients with Wegener's granulomatosis (WG). METHODS: Serum neopterin was measured by radioimmunoassay, sTNF-55R and sIL-2R were measured by ELISA in 26 patients with WG. RESULTS: Serum neopterin, sTNF-55R, and sIL-2R were significantly elevated in patients with generalized WG compared with healthy controls. Concentrations of the analytes correlated with disease activity indices in patients without infectious complications. The highest elevations of all 3 variables were observed in patients with intercurrent infections. CONCLUSION: The increased serum levels of neopterin, sTNF-55R, and sIL-2R suggest activation of cellular immunity in WG.  相似文献   

20.
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