Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease.

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87 percent accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100 percent), but with reduction in diagnostic sensitivity (64 percent). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70 percent). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

[Serum concentration of bile acids in the diagnosis of chronic liver disease and in the functional staging]. / Determinação sérica dos ácidos biliares na detecção da hepatopatia crônica e no seu estadiamento funcional.

The serum values of the total biliary acids were dosed through the enzymatic-colorimetric method in 15 dyspeptic persons with no hepatic disease (control-group) and in 52 patients with chronic hepatic disease of alcoholic etiology, subdivided according to the Child-Pugh functional classification (Child A = 17; Child B = 18, and C = 17) or according to the clinic exam in one compensated group (n = 22) and in one decompensated group (n = 30). The serum dosages of the biliary acids, particularly the posprandial ones, presented high discriminative power in the detection of chronic hepatopathy, separating the control-group from any of the other groups of alcoholic patients with chronic hepatopathy. The dosages also presented significant correlation with the biochemical tests more directly related to the hepatocellular function, as albumin, total bilirubin and the activity of prothrombin, besides the Child-Pugh numeric score classification. Nevertheless, when the cirrhotic patients were separated in accordance with the clinical presentation, the serum dosage of the biliary acids presented inferior discriminative capacity in relation to the conventional exams as the Child-Pugh numeric classification and the time of prothrombin. Therefore, demonstrating to have limited value in the functional evaluation and in the evolutional following-up of the alcoholic chronic hepatopathy.

Fibronectin in the ascitic fluid of cirrhotic patients: correlation with biochemical risk factors for the development of spontaneous bacterial peritonitis.

Cirrhotic patients (23 with alcoholic cirrhosis, 5 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis) with ascites and portal hypertension were studied and divided into two groups corresponding to high or low risk to develop spontaneous bacterial peritonitis (SBP) related to the concentration of total protein in the ascitic fluid (A-TP): group I (high risk): A-TP < or = 1.5 g/dl and group II (low risk): A-TP > 1.5 g/dl. Fibronectin (FN), C3 and C4 concentrations were measured by radial immunodiffusion while total protein was measured by the biuret method. The mean values (group I vs group II) of C3 (12.59 +/- 4.72 vs 24.53 +/- 15.58 mg/dl), C4 (4.26 +/- 3.87 vs 7.26 +/- 4.14 mg/dl) and FN (50.47 +/- 12.49 vs 75.89 +/- 24.70 mg/dl) in the ascitic fluid were significantly lower (P < 0.05) in the group considered to be at high risk for SBP. No significant difference was observed in the plasma/ascites fibronectin ratio (3.91 +/- 1.21 vs 3.80 +/- 1.26) or gradient (131.46 +/- 64.01 vs 196.96 +/- 57.38) between groups. Fibronectin in ascites was significantly correlated to C3 (r = 0.76), C4 (r = 0.58), total protein (r = 0.73) and plasma FN (r = 0.58) (P < 0.05). The data suggest that the FN concentration in ascites is related to the opsonic capacity of this fluid, and that its concentration in the ascitic fluid may be a biochemical risk factor indicator for the development of spontaneous bacterial peritonitis.

Fibronectin in the ascitic fluid of cirrhotic patients: correlation with biochemical risk factors for the development of spontaneous bacterial peritonitis

Cirrhotic patients (23 with alcoholic cirrhosis, 5 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis) with ascites and portal hypertension were studied and divided into two groups corresponding to high or low risk to develop spontaneous bacterial peritonitis (SBP) related to the concentration of total protein in the ascite fluid (A-TP): group I (high risk): A-TP=1.5 g/dl and group II (low risk): A-TP>1.5 g/dl. Fibronectin (FN), C3 and C4 concentrations were measured by radial immunodiffusion while total protein was measured by the biuret method. The mean values (group I vs group II) of C3 (12.59+ 4.72 vs 24.53 + 15.58 mg/dl), C4 (4.26 + 3.87 vs 7.26 + 4.14 mg/dl) and FN (50.47 + 12.49 vs 75.89 + 24.70 mg/dl) in the ascitic fluid were significantly lower (P<0.05) in the group considered to be at high risk for SBP. No significant difference was observed in the plasma/ascites fibronectin ratio (3.91 + 1.21 vs 3.80 + 1.26) or gradient (131.46 + 64.01 vs 196.96 + 57.38) between groups. Fibronectin in ascites was significantly correlated to C3 (r = 0.76), C4 (r = 0.58), total protein (r = 0.73) and plasma FN (r = 0.58) (P<0.05). The data suggest that the FN concentration in ascites is related to the opsonic capacity of this fluid, and that its concentration in the ascitic fluid may be a biochemical risk factor indicator for the development of spontaneous bacterial peritonitis.

The predictive value of serum laminin for the risk of variceal bleeding related to portal pressure levels.

BACKGROUND/AIMS: This paper presents the results of the radioimmunologic determination of laminin in serum of patients with alcoholic liver cirrhosis with a preserved hepatic function, trying to evaluate its predictive value for the risk of variceal bleeding, assessed by a portal pressure level equal to or higher than 12 mmHg. PATIENTS AND METHODS: Twenty alcoholic cirrhotic patients with a preserved hepatic function as assessed by the Child-Pugh classification, had their peripheral blood taken for radioimmunological determination of serum laminin and were submitted to hepatic vein catheterization for portal pressure measurement. RESULTS: A positive and significant correlation (r = 0.70, p < 0.001) was found between serum laminin levels (mean value + SD = 2.70 + 1.13 U/ml) and hepatic vein pressure gradient (mean HVPG + SD = 16.30 + 6.06 mmHg). Such correlation prompted us to find a value for the level of laminin that more closely represented a HVPG of 12 mmHg, a well known threshold pressure for esophageal varices bleeding. At a cut-off concentration for laminin of 2.19 U/ml, sensitivity was 73%, specificity 60%, the positive predictive value was 85% and the negative predictive value 43%. In this study population, with a prevalence of 75% of a HVPG > or = 12 mmHg, the diagnostic accuracy for such levels of serum laminin was 70%. CONCLUSIONS: Although a valid attempt in having a non invasive parameter for the investigation of portal hypertension, peripheral serum laminin alone doesn't seem to be a reliable marker for predicting portal hypertension and to assess the risk of variceal bleeding in patients with alcoholic cirrhosis.

Colchicina na doença hepática crônica de etiologia alcoólica. Estudo duplo-cego, randomizado, de seus efeitos sobre os níveis séricos das proteínas plasmáticas e evoluçäo clínica dos pacientes / Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on the serum levels of plasma proteins and clinical evolution of the patients

Pacientes portadores de hepatopatia crônica de etiologia alcoólica, quando tratados com colchicina durante período de 12 meses, apresentaram índices de recuperaçäo dos níveis plasmáticos de albumina e protrombina significantemente superiores aos de pacientes fazendo uso de placebo. Entretanto, nenhuma diferença estatística pôde ser observada entre os dois grupos quanto à taxa de mortalidade e de admissäo hospitalar dos pacientes, no período estudado. OBJETIVO. Analisar a evoluçäo clínica e os níveis plasmáticos de albumina, pré-albumina, transferrina e protrombina em portadores de hepatopatia crônica alcoólicaem uso de colchicina ou placebo, durante período de 12 meses. MÉTODOS. em um estudo duplo-cego, 41 pacientes portadores de hepatopatia crônica de etiologia alcoólica foram randomizados para receber placebo (20 pacientes) ou colchicina (21 pacientes), avaliando sua evoluçäo clínica e dos níveis das proteínas plasmáticasalbumina, pré-albumina e transferrina por imunodifusäo radial e do tempo e atividade de protrombina pelo método de Quick modificado. RESULTADOS. Apenas 7,3 por cento dos pacientes näo completaram os 12 meses de seguimento do estudo. Näo se observaram diferenças significantes entre os grupos, no que se refere à taxa de mortalidade ou ao número de internaçöes hospitalares. Quanto aos níveis séricos protéicos, observaram-se valores significantemente superiores no grupo da colchicina do que no grupo placebo, para as médias das variaçöes percentuais dos níveis de albumina (17,9 por cento colchicina x 3,6 por cento placebo, p<0,05) e da atividade de protrombina (19,2 por cento colchicina x 2,1 por cento placebo, p<0,05). As variaçöes dos valores da pré-albumina, apesar de apresentarem o mesmo comportamento observado para os níveis de albumina e protrombina, näo atingiram significância estatística. Já os níveis de transferrina sérica näo diferiram entreos dois grupos. CONCLUSÄO. Estes resultados sugerem que a administraçäo de colchicina tenha um efeito benéfico sobre os níveis de proteínas plasmáticas nos pacientes com hepatopatia crônica de etiologia alcoólica.

[Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients]. / Colchicina na doença hepática crônica de etiologia alcoólica. Estudo duplo-cego, randomizado, de seus efeitos sobre os níveis séricos das proteínas plasmáticas e evolução clínica dos pacientes.

UNLABELLED: Patients with alcoholic chronic liver disease when treated with colchicine during a 12 month-period improved significantly the plasmatic levels of albumin and prothrombin when compared with a similar group of patients who took placebo. No differences in the mortality rate and in number of patients admitted at the hospital could be detected among those groups during this period. PURPOSE: To evaluate the clinical outcome and the plasmatic levels of albumin, pre-albumin, prothrombin and transferrin in patients presenting alcoholic chronic liver disease taking colchicine or placebo, during a 12-month period. METHODS: In a double-blind, randomized, controlled trial, 41 patients with alcoholic chronic liver disease were assigned to either placebo (20 patients) or a colchicine (21 patients) treatment group, assessing their clinical course (mortality rate and hospital admission) and plasmatic protein levels during a 12-month period. Albumin, pre-albumin and transferrin plasmatic levels were assessed through a immunodiffusion radial method and prothrombin time and activity was assessed by a one stage Quick modified method. RESULTS: At the end of the trial, only 7.3% of the patients were lost during follow-up. No statistical differences could be found in mortality and number of patients admitted at the hospital among placebo and colchicine groups. Comparatively to the placebo group, a significant increase in the mean of percentage variation was found in patients of the colchicine group for serum albumin levels (17.9% colchicine x 3.6% placebo, p < 0.05) and for prothrombin activity (19.2% colchicine x 2.1% placebo, p < 0.05). A similar pattern of response was found in pre-albumin serum levels, but such differences were not statistically different. No differences were found in serum transferrin levels among both groups. CONCLUSION: These results suggest that colchicine intake has a positive effect on plasmatic protein levels in patients with alcoholic chronic liver disease.

Parasite and egg burden, hepatic collagen and histologic pattern of liver granulomas in selection III high and low antibody responder mice infected with Schistosoma mansoni

Selection III mice have particular immunological characteristics: they are high (H III) or low (L III) antibody producer animals, yet both lines display similar T cell responses and macrophage activities. We submittedthese mice to infection with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic collagen and cellular composition of granulomas in both lines. Titration of anti-Schistosoma IgG by ELISA showed remarkably higher values inH III line, at both studied periods (8th and 12th weeks post-infection). Nevertheless, the number of adult worms recovered from the portal system was similar inboth lines, being not associated with anti-Schistosoma antibody levels. There isan increase in hepatic collagen from the 8th to the 12th weeks post-infection, which is paralleled by an increase in the number of eggs in the liver. This association apparently occurs at the same radio in H III and L III animals. The most important difference found between the two lines was the outstanding contrast interms of volume and eosinophil counts in the granulomas, with lesions from H IIImice clearly being larger and containing more of these cells than LIII lesions

Effects of vitamin A administration on collagen and sulfated glycosaminoglycans contents in the livers of rats treated with carbon tetrachloride.

We have investigated the effects of nontoxic doses of vitamin A on the hepatic contents of collagen and sulfated glycosaminoglycans (SGAGs) in rats chronically treated with CCl4. When the animals were treated with this retinoid before the intoxication with CCl4, liver collagen level was significantly reduced as compared with that in rats that received only CCl4 (3.31 +/- 0.40 vs 5.00 +/- 0.61 mg/gm wet liver, mean +/- SD, respectively), although no significant differences were found for the relative proportion of type III collagen related to type I collagen. The absolute increment in the total amount of liver SGAG in the vitamin A--pretreated group was followed by a more important increase in the concentration of dermatan sulfate as compared with the CCl4 group (dermatan sulfate-to-heparan sulfate ratio: 1.15 for the CCl4 group vs 1.70 for the vitamin A--pretreated group). A significant proportion of the dermatan sulfate from this last group was of higher molecular weight when compared with the dermatan sulfate found in the liver of rats that received only CCl4. Our results indicate that the pretreatment with vitamin A modifies hepatic collagen and SGAG deposition and can inhibit or delay the development of liver cirrhosis in rats chronically treated with CCl4. We speculate that this effect could be due to the changes in the fat-storing (Ito) cells phenotype induced by vitamin A.

Serum laminin in hepatosplenic human schistosomiasis.

Serum laminin level was measured in chronic hepatic schistosomiasis. A significant increase in the mean serum laminin levels was observed in patients with hepatosplenic (HS) schistosomiasis (2.57 +/- 0.83 U/ml), as compared to those in patients with the hepatointestinal (HI) form of the disease (1.38 +/- 0.45-U/ml) and in the control group (1.15 +/- 0.31 U/ml). In the HS patients there was a significant direct relation between serum laminin and percutaneous splenic pulp pressure (r = 0.68). These findings are compatible with an increased production of laminin in hepatosplenic schistosomiasis with may be related to the observed enlarged liver and spleen basement membranes in such disease.

Serum laminin in hepatosplenic human schistosomiasis

Serum laminin level was measured in chronic schistosomiasis. A significant increase in the mean serum laminin levels was observed in patients with hepatosplenic (HS) schistosomiasis (2,57 ñ 0,83U/ml), as compared to those in patients with the hepatointestinal (HI) form of the disease (1,38 ñ 0,45-U/ml) and in the control group (1,15 ñ 0,31 U/ml). In the HS patients there was a significant direct relatiom between serum laminin and percutaneous splenic pulp pressure (r = 0,68). These findigs are compatible with an increased production of lamin in hepatosplenic schistosomiasis with may be related to the observed enlarged liver and spleen basement membranes in such disease