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1.
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   

2.
Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.  相似文献   

3.
Transforming growth factor (TGF)-beta 1 is an important cytokine involved in the pathobiology of tissue fibrosis through its stimulation of the production of, and inhibition of the degradation of, extracellular matrix proteins. We examined the clinical usefulness of plasma TGF-beta 1 concentration as a marker of fibrogenesis in patients with chronic viral hepatitis. Thirty-five patients, 11 with minimal chronic hepatitis, 14 with mild chronic hepatitis and 10 with moderate chronic hepatitis and 20 healthy subjects were studied. Transforming growth factor-beta 1 concentrations in platelet-poor plasma were measured with a TGF-beta 1 enzyme-linked immunosorbent assay system kit after acid-ethanol extraction. Plasma TGF-beta 1 levels were significantly elevated in patients with mild and moderate chronic hepatitis, but not in those with minimal chronic hepatitis, compared with the levels in the controls. Plasma TGF-beta 1 levels were increased in parallel with the histological degree of necroinflammation and of liver fibrosis. Plasma TGF-beta 1 levels were positively correlated with blood levels of procollagen type III N-peptide, and 7S fragment and central triple-helix of type IV collagen. These results suggest that plasma TGF-beta 1 level is a useful marker in assessing the situation of liver active fibrogenesis in patients with chronic viral hepatitis.  相似文献   

4.
Tumor markers have been used for the evaluation of various malignancies though the existence of false positive results in some benign diseases is known. In this study, several established markers including carcinoembryonic antigen, alpha fetoprotein, beta human chorionic gonadotropin, ferritin, CA 19-9 and CA 125 were measured in 60 patients with chronic active hepatitis, 70 patients with cirrhosis and 40 normal subjects in order to evaluate the rate of false elevation of tumor markers in chronic liver disease. Prostate specific antigen and prostatic acid phosphatase levels were also measured in male patients and controls. Serum alpha fetoprotein levels were found elevated in 20% of patients with cirrhosis. The serum CA 19-9 level showed significant elevation in chronic active hepatitis (32%) and cirrhosis (44%). Increase in CA 125 concentration was also remarkable in chronic active hepatitis (23%) and especially in cirrhosis (74%). These results indicate that it is necessary to consider the presence of high false positivity rate of CA 19-9 and CA 125 during clinical interpretation of tumor markers in patients with chronic liver disease.  相似文献   

5.
Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.  相似文献   

6.
Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long term administration.  相似文献   

7.
BACKGROUND/AIMS: The response to interferon therapy for chronic hepatitis is known to decrease with progression of the hepatic fibrosis. On the other hand, serum hyaluronate reflects hepatic sinusoidal capillarization or liver cirrhosis, and also serum type IV collagen, which is one of the main components of the basement membrane, rises with the progression of hepatic fibrosis. In this study, the relationship between the degree of hepatic fibrosis and the response to interferon-alpha was determined retrospectively in patients with chronic hepatitis C. In addition, whether the measurement of serum hyaluronate and type IV collagen before interferon-alpha therapy was useful for predicting the response to interferon-alpha therapy in chronic hepatitis C was determined. MATERIALS AND METHODS: Thirty-seven patients with elevated serum ALT levels for at least 6 months and histologically determined chronic hepatitis were studied. All patients were positive for anti-HCV and negative for hepatitis B surface antigen. Twenty-eight healthy adults with normal blood biochemical data, who were negative for hepatitis B antigen and HCV antibody tests, had limited alcohol intake were used as controls. The test group was given IFN-alpha by intramuscular injection for 14 days, and then were treated 3 times per week for 24 weeks. RESULTS: The extent of hepatic fibrosis, particularly, perisinusoidal fibrosis (P < 0.01) was significantly greater in nonresponders than in responders. The mean serum hyaluronate and type IV collagen levels were more elevated in nonresponders than in responders, especially, the serum hyaluronate level showed a significant difference (P < 0.01). Most of the patients having a serum hyaluronate level of more than 100 ng/ml were nonresponders who had chronic active hepatitis with bridging necrosis on liver biopsy. Serum hyaluronate and type IV collagen levels showed significant positive correlation with degree of the portal fibrosis (P < 0.01), perisinusoidal fibrosis (P < 0.001) and focal necrosis (P < 0.01) in histological findings of liver biopsy specimens. CONCLUSION: These results suggest that serum hyaluronate and type IV collagen levels reflect the extent of the hepatic fibrosis in chronic hepatitis C and also that serum hyaluronate level predicts the response to interferon-alpha therapy in patients with chronic hepatitis C.  相似文献   

8.
Hepatitis frequently recurs after liver transplantation for hepatitis C. However, the histological progression of disease, predictors of recurrence and disease severity, and patient survival remain uncertain. Fifty-five patients with cirrhosis caused by chronic hepatitis C underwent liver transplantation between January 1990 and December 1993. Hepatitis C genotype was determined, and liver biopsies were performed at frequent intervals posttransplantation. The median follow-up time was 40.4 months. The cumulative rate of survival was no different in liver transplant recipients for hepatitis C than in liver transplant recipients for other chronic liver diseases (P = .62). Histological recurrent hepatitis C developed in 33 of 50 patients assessable for disease recurrence; the median recurrence-free survival time was 13.4 months. Histological activity and stage were mild in most cases. Only 2 patients developed cirrhosis, and no patient required a second transplantation for recurrent disease. Patients with acute cellular rejection had a shorter recurrence-free survival (P = .0141). In patients with recurrent hepatitis, rejection also was correlated with increased histological grade 2 years after transplantation (P = .0061). Recurrence-free survival was decreased in patients infected with genotype 1 (1a and 1b combined) compared with genotypes 2 and 3 combined (P = .02), whereas there was no difference between genotypes 1a and 1b (P > .80). Only patients infected with genotype 1a or 1b developed bridging fibrosis or cirrhosis. In addition, patients who had an early recurrence had a greater risk of progressing to bridging fibrosis or cirrhosis (hazard ratio, 5.1; P = .0473). In our experience, recurrent hepatitiS C after liver transplantation in most cases is mild and survival is unaffected. Both acute cellular rejection and infection with genotype 1 are independent risk factors for reduced recurrence-free survival, and early recurrence is associated with a higher risk of disease progression.  相似文献   

9.
10.
BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is one of the most important diseases with high chronicity rate (50-80%) leading to end-stag cirrhosis and hepatocellular carcinoma. Hepatic histology shows a characteristic but not diagnostic picture. The aim of this study was to evaluate the characteristic histological findings in correlation with epidemiological features in our liver biopsy material. PATIENTS/METHODS: 106 liver biopsies were studid between 1993-1996. All patients (60 males, 46 females, age between 11-81 years, mean age: 43 years) were found to be positive for HCV antibody by a second-generation ELISA method. The biopsy materials were fixed in buffered formalin and having embedded in paraffin, stained with hematoxylin and eosin, periodic acid-Schiff after diastase digestion, G?m?ri's reticulin stain and picrosirius red for collagen. The histological evaluation was based upon the new classification of chronic hepatitis proposed by Desmet et al. The statistical analysis was performed by the Chi square test. RESULTS: Minimal chronic hepatitis (HAI: 1-3) was found in 14 (13.2%), mild chronic hepatitis (HAI: 4-8) in 69 (65.09%) and moderate chronic hepatitis (HAI: 9-12) in 23 (21.69%) cases, while assessment of fibrosis (staging) resulted fibrosis 0/1 in 44 (41.5%), fibrosis 2 in 14 (13.2%), fibrosis 3 in 37 (34.9%) and cirrhosis (fibrosis 4) in 11 (10.37%) cases. Among histological features of chronic hepatitis C, the frequency of steatosis (70.75%), lymphoid F/A (63.2%), and bile duct lesions (12.26%) have paralelly increased with activity (grade) of hepatitis and these changes were more pronounced in moderate chronic hepatitis (p < 0.001). CONCLUSIONS: More than half of chronic hepatitis C patients presented mild histological lesions with stage 1 fibrosis. Lymphoid F/A, bile duct damage and steatosis are important diagnostic features that show a strong correlation with the activity of chronic hepatitis. The assessment of fibrosis (stage: 3 and stage: 4) in mild chronic hepatitis cases does alert the hepatologist to perform the liver biopsy to detect the fibrotic changes in chronic hepatitis C.  相似文献   

11.
Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)2D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3 delta pH. Urinary pyridinoline (Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.  相似文献   

12.
AIM: To evaluate the prevalence of iron overload in chronic hepatitis C and its relationship with liver histology. PATIENTS AND METHODS: Serum iron, unsaturated iron binding capacity and ferritin levels were determined in 204 consecutive anti-hepatitis C virus positive subjects, whereas hepatic iron concentration, hepatic histological grading and staging, hepatitis C virus genotypes were further assessed in a subgroup of 50 patients who underwent liver biopsy for chronic hepatitis. RESULTS: An increase in the serum markers of iron metabolism was more frequently found in subjects with aminotransferase activities above the normal range, whereas hepatic iron overload, established by direct hepatic iron determination, was found only in 9/50 (18%) patients with chronic hepatitis C. No serum iron marker could reliably predict hepatic iron stores. Patients with mild iron overload usually showed active hepatitis and fibrosis, whereas iron overload was not present in patients without fibrosis or with very mild fibrosis. Two out of nine patients with iron overload were shown to be beta thalassaemia heterozygous, and two were heterozygous carriers of a putative haemochromatosis gene mutation (His63Asp). CONCLUSIONS: Many anti-hepatitis C virus positive patients with elevated aminotransferase activities have serum ferritin levels above the normal range, but only a minority of patients with chronic hepatitis C have a mild iron overload. In chronic hepatitis C, a relationship does exist between hepatic iron content and liver fibrosis.  相似文献   

13.
BACKGROUND/AIMS/METHODS: The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS: Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS: Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.  相似文献   

14.
Data from the past few years have shown that as caffeine metabolizes solely in the liver, caffeine elimination can serve as a liver function test. We have collected data by monitoring 40 persons with liver diseases (11 chronic alcoholic hepatitis, 24 liver cirrhosis, 5 non-cirrhotic liver disease). Eight subjects served as controls. The patients with liver cirrhosis were classified according to the Child--Pugh scoring system. To determine caffeine elimination blood samples were collected before and at 3, 6, 9 and 12 hours after oral administration of 0.2 g caffeine. Fasting serum caffeine concentration and concentration 12 hours after administration, serum clearance, half life, peak concentration and volume of distribution have been compared. The respective values measured in patients with non-cirrhotic liver diseases did not differ significantly from the controls. The disappearance of caffeine was significantly decreased in cirrhotics. Our results demonstrated a good correlation between impairment of caffeine elimination and assessment of severity of liver disease by the Child--Pugh classification. Measuring serum levels in samples taken 12 hours after caffeine administration is a simple and useful method in the diagnosis of liver diseases at cirrhotic stage.  相似文献   

15.
BACKGROUND/AIMS: Chronic hepatitis C appears to have a highly variable natural course with 20% of patients developing cirrhosis within 20 years, while the majority of them run a relatively mild course. We studied the relationships of epidemiological, biochemical and virological features with histological severity (grade) and liver disease progression (stage). METHODOLOGY: Liver histology, serum HCV RNA level and HCV genotype were determined in a well-defined cohort of 152 consecutive (100 males, 52 females) patients with chronic hepatitis C. RESULTS: Patients with minimal or mild chronic hepatitis were significantly younger than those with moderate or severe chronic hepatitis (mean age: 41.1 vs 49.5 years respectively, p=0.003). On the other hand, patients with no or mild fibrosis compared to those with moderate or severe fibrosis and to those with cirrhosis were significantly more frequently males (73%, 64% and 43%, p=0.01), parenteral drug users (36%, 11% and 11%, p=0.01) and infected with other than 1b genotype (86%, 52% and 33%, p<0.0001), significantly younger (mean age: 37, 48 and 58 years, p<0.0001) and had significantly lower HCV RNA levels (geometric mean: 6.9, 19.2 and 17.5 x 10(5) eq/ml, p=0.007). Multivariate analysis showed that stage was significantly related only to patient age (p<0.0001), HCV genotype (p=0.0025) and HCV RNA level (p=0.044). CONCLUSIONS: In chronic hepatitis C, histological severity seems to be associated only with patient age, while progression of the disease is mainly associated with patient age, HCV genotype and viremia level.  相似文献   

16.
"Cures" embrace by definition a broad spectrum starting from taking waters in health resorts to hospital treatment in modern rehabilitation centers. The effectiveness of traditional cure procedures is discussed. Effectiveness of drinking cures, baths and mud packs in liver disease has not yet been proven. Controlled trials are necessary. Clinical treatment is indicated in alcoholic liver damage, viral hepatitis with a protracted course, chronic aggressive hepatitis and compensated cirrhosis of the liver; such treatment, however, is questionable in fatty liver and in chronic persistent hepatitis. Data concerning the effectiveness of treatment of chronic liver diseases are given. The following conclusions are drawn: patients with liver disease ought to be hospitalized when undergoing cures, indications have to be precised, collaboration of patients has to be stimulated, hospital discipline has to be tight, therapy of alcoholism has to include several psychosocial aspects, treatment after leaving hospital has to be improved.  相似文献   

17.
To clarify the clinical significance of vitronectin, we compared the concentration of plasma vitronectin with serum fibrous markers and liver function test values in patients with chronic liver diseases. We also evaluated the vitronectin content in the liver by means of enzyme-linked immunosorbent assay and the localization of vitronectin in liver tissue with enzyme immunohistochemistry. In chronic liver disease, the concentration of plasma vitronectin was significantly lower than that in healthy controls, being related to the severity of liver disease. The plasma levels of vitronectin showed no correlation to fibrous markers but a significant correlation with those of serum albumin and prothrombin time. On the other hand, the content of vitronectin in liver tissue was significantly increased in chronic liver disease compared with that in normal controls. In the normal liver, vitronectin was observed in the portal area by light microscopy. In chronic hepatitis and cirrhosis, vitronectin was found in the connective tissue around the portal and central veins and in the areas of piecemeal and focal necrosis. These findings suggested that vitronectin is deposited in injured tissue through the process of repair and fibrosis and plays an important role as an adhesive protein. Moreover, the lower levels of plasma vitronectin in chronic liver disease may be due to its decreased synthesis, deposition or both in injured tissue.  相似文献   

18.
Ursodeoxycholic acid (UDCA or ursodiol) administration has been associated with a reduction of serum liver enzymes in patients with chronic liver disease and with improvement of liver histology in patients with primary biliary cirrhosis. To establish the potential therapeutic efficacy of ursodiol in chronic hepatitis, serum biochemistry and liver histology were investigated in a multicenter, double-blind placebo controlled clinical trial. Sixty patients with non-cholestatic chronic active (mild or severe) hepatitis, mainly of viral (virus C) etiology and almost completely asymptomatic, were enrolled in 3 centers: 29 were assigned to receive placebo and 31 UDCA (600 mg/day) for 1 year. Demographic, biochemical, virological and histological features were balanced between the 2 groups at the entrance into the study. Fifty-six patients (34 males, 22 females; 19 with cirrhosis; 5 HBsAg-positive; 45 anti-HCV positive) were included in the final analysis. Compliance was checked by measuring UDCA levels at the 3 follow-up visits (3, 6 and 12 months). Liver biopsy was performed at the beginning and at the end of treatment and was evaluated blindly by our pathologist (F.C.). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyltransferase (GGT) levels were significantly reduced by 25% from baseline values during treatment with ursodiol but not with placebo. The efficacy of UDCA in lowering serum AST and ALT was more pronounced in the presence of cirrhosis. The semiquantitative liver histological score used remained substantially unchanged after treatment and no differences between placebo and UDCA were found for portal or periportal necrosis or inflammation, intralobular degeneration, cholestasis or fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

19.
The nonenzymatic conjugation of metabolites is decreased in chronic diseases of the liver, which is caused by decreased concentration of glutathione. The activities of glutathione enzymes are increased, this indicating the development of compensatory processes of mobilization of the second phase of detoxication, that is, increased conjugation under conditions of suppression of the cytochrome P-450 system. Measurement of liver glutathione transferase is a highly informative test for assessing the activity of the pathological process, particularly important in patients with chronic active hepatitis and cirrhosis of the liver.  相似文献   

20.
Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and gamma-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.  相似文献   

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