Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. METHODS: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. RESULTS: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p < 0.001; LN: r = 0.610, p < 0.001). There were significant differences of serum HA and LN levels between F2-4 group in comparison with those in F0-F1 group (p < 0.001) and controls (p < 0.001), respectively. From ROC curves, 185.3 ng/mL as the optimal cut-off value of serum HA for diagnosis of significant fibrosis, giving its sensitivity, specificity, PPV, NPV, LR+, LR- and AC of 84.2 percent, 83.3 percent, 90.6 percent, 73.5 percent, 5.04, 0.19 and 83.9, respectively. While 132.7 ng/mL was the optimal cut-off value of serum LN, the sensitivity, specificity, PPV, NPV, LR+, LR- and AC were 71.9 percent, 80.0 percent, 87.2 percent, 60.0 percent, 3.59 percent, 0.35 percent and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100 percent, at the same time sensitivity declined to 63.2 percent and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7 percent, NPV to 86.4 percent, and LR- declined to 0.08. CONCLUSIONS: Serum HA and LN concentrations showed positive correlation with the stages of liver fibrosis. Detection of serum HA and LN in predicting significant fibrosis showed good diagnostic performance, which would be further optimized by combination of the two indices. HA and LN would be clinically useful serum markers for predicting significant fibrosis in patients with chronic hepatitis B, when liver biopsy is contraindicated.

Comparison and validation of laminin-based score and fibroscan for prediction of liver fibrosis in Egyptian patients with chronic hepatitis C

The constraints of liver biopsy and the limitations of single parameters in assessing liver fibrosis have boosted the development of scores combining markers to improve accuracy. Laminin-based score was devised by the study group in 2006. The present study was conducted to validate the diagnostic accuracy of this score and of transient elastography [T.E.] In another group of ninety Egyptian patients with chronic hepatitis C. Patients were biopsied and subjected to assessment of score parameters [serum albumin, AST, prothrombin concentration, laminin, portal vein diameter] and liver stifihess by T.E. Patients were classified using modified Knodell score into 7 groups [stage 0-stage 6]. A significant relation between the stage of fibrosis and the laminin-based score was found. The score demonstrated high accuracy for diagnosing significant fibrosis and cirrhosis. Liver stiffness correlated significantly with staging of fibrosis as well as with laminin-based score. T.E. demonstrated high accuracy for diagnosing significant fibrosis and cirrhosis. Both methods proved useful to discriminate stages F4 and F5. When both methods were combined, the diagnostic accuracy was increased to 93.7% for diagnosing significant fibrosis. Laminin-based score and T.E. Proved their clinical value and may reduce the need for repeated liver biopsies

Ascorbic Acid Alleviates Pancreatic Damage Induced by Dibutyltin Dichloride (DBTC) in Rats

PURPOSE: Because previous studies have reported depleted antioxidant capacity in patients with chronic pancreatitis (CP), prevention of free radical production has gained importance in antifibrotic treatment strategies for CP. The aim of this study was to investigate the effects of ascorbic acid on oxidative capacity and pancreatic damage in experimental CP. MATERIALS AND METHODS: CP was induced in male Sprague-Dawley rats by infusion of dibutyltin dichloride (DBTC) into the tail vein. Ascorbic acid was given intraperitoneally at a daily dose of 10mg/kg body weight. The treatment groups were as follows: group 1, DBTC plus intraperitoneal physiologic saline; group 2, DBTC plus intraperitoneal ascorbic acid; group 3, solvent plus intraperitoneal physiologic saline; group 4, no operation plus intraperitoneal physiologic saline. Each group contained 15 animals. Treatment was started after CP was established. After 4 weeks of treatment, serum hyaluronic acid and laminin levels were determined by radioimmunoassay, pancreatic tissue oxidative stress was analyzed, and the degree of pancreatic damage was determined. RESULTS: Ascorbic acid treatment markedly increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) concentrations in pancreatic tissue (p < 0.01 for both). Significant serum hyaluronic acid and laminin reductions were observed in group 2 as compared with group 1 (p < 0.05). However, the serum hyaluronic acid and laminin levels remained elevated when compared with those of groups 3 and 4 (p < 0.05). Histopathologic scores were also lower in animals with CP that underwent ascorbic acid-treatment (p < 0.05). CONCLUSION: Ascorbic acid treatment alleviated the degree of oxidative stress and pancreatic damage in rat CP. Antioxidant treatment might be considered a potential option to improve the pathologic process in CP.

High serum laminin and type IV collagen levels in schistosomiasis mansoni

RACIONAL: A fibrose hepática é caracterizada por um aumento progressivo na quantidade do tecido conjuntivo hepático, que é formado pelo aumento na deposição de componentes da matriz extracelular, tendo sido encontrada grande quantidade desses componentes no fígado de pacientes com esquistossomose mansoni. A laminina e o colágeno tipo IV têm sido investigados em várias doenças hepáticas, mas seu papel na esquistossomose ainda não está esclarecido. OBJETIVOS: Avaliar a fibrose hepática na esquistossomose mansoni através da determinação sérica de laminina e colágeno tipo IV, considerados marcadores séricos de fibrose hepática. PACIENTES E MÉTODOS: Foram incluídos 82 indivíduos, sendo 18 indivíduos normais, como controle e 64 pacientes com esquistossomose mansoni, em suas diferentes formas clínicas: intestinal (grupo I), hepatointestinal (grupo II), hepatoesplênica compensada (grupo III) e hepatoesplênica descompensada (grupo IV). Os níveis séricos de laminina e colágeno tipo IV foram determinados por método imunoenzimático sanduíche. RESULTADOS: Os valores médios de colágeno tipo IV e laminina estiveram significativamente aumentados em pacientes com esquistossomose, quando comparados com os controles. Em relação às formas clínicas, os níveis séricos de colágeno tipo IV estiveram significativamente aumentados nos grupos II e IV, em relação aos controles e entre as formas hepatoesplênica descompensada e intestinal. Os níveis séricos de laminina estiveram significativamente aumentados nos grupos II, III e IV e entre o grupo IV e II. Não foi encontrada correlação entre os valores médios de colágeno tipo IV e laminina com o grau de espessamento periportal, detectado por ultra-sonografia. Foi encontrada correlação positiva entre colágeno tipo IV e laminina nos grupos II e IV. CONCLUSÕES: Os resultados mostram que existe aumento de produção de colágeno tipo IV e laminina na esquistossomose mansoni, surgindo altos níveis desde as fases iniciais do envolvimento hepático da doença, até as formas mais avançadas, sugerindo ser um útil fator para detecção de progressão da doença.

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.

Laminin concentration in ascites of patients with hepatic cirrhosis and peritoneal carcinomatosis

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 ± 0.5 vs 2.1 ± 0.4 æg/ml, mean ± SD, P < 0.05) and ascites (2.8 ± 0.5 vs 1.6 ± 0.4 æg/ml, P < 0.05). Although laminin concentration was higher in serum than in ascites, the laminin serum/ascites ratio and serum-ascites gradient did not differ between the studied groups. A significant correlation (r = 0.93, P < 0.0001) was observed between the serum and ascites laminin values. Serum laminin levels >2.25 æg/ml showed 100 percent sensitivity and 73 percent specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.

Detection of laminin in serum and ascites from patients with epithelial ovarian tumor / 华中科技大学学报（医学）（英德文版）

The change in serum laminin (LN) level and its clinical significance in epithelial ovarian tumor were investigated. The LN levels in serum and ascites samples from 69 patients with epithelial ovarian tumor and 42 cases as control group before and after operation were analyzed by radioimmunoassay. The results showed that the serum LN levels in the patients with malignant tumors (157.85 +/- 14.37 ng/ml) were significantly higher than that in the control group (125.14 +/- 7.03 ng/ml) and in the patients with benign tumors (128.36 +/- 8.75 ng/ml) (both P < 0.01) before operation. The serum LN levels in the malignant group were decreased significantly after operation as compared with those before operation (P < 0.05). The serum LN levels in low-differentiated tumors was higher than those in moderate-differentiated tumors and high-differentiated tumors (P < 0.05). The LN levels in ascites (172.94 +/- 15.26 ng/ml) was significantly higher than in serum (161.34 +/- 6.59 ng/ml) (P < 0.05) in malignant tumors. The serum LN levels in the patients with lymph node metastasis (165.41 +/- 19.91 ng/ml) was obviously higher than those without lymph node metastasis (152.35 +/- 10.34 ng/ml) (P < 0.05). It was concluded that LN levels in serum and acistis were remarkably increased in malignant epithelial ovarian tumors, suggesting that LN might be one of important diameters reflecting tumor biological characteristics.

Serum laminin P1 and procollagen III peptide in egyptian children with chronic hepatopathies

Hepatic fibrosis, commonly present in chronic liver diseases, is a leading cause of morbidity and mortality through the resultant portal hypertension and hepatocellular dysfunction. To study the diagnostic significance of serum procollagen III peptide [P III P] and laminin PI [Lam PI] in Egyptian children with chronic hepatopathies, these two fibrogenesis markers were measured in 80 children [6-12 years old], 10 healthy controls, 20 with pure bilharziasis [group 1], 15 with chronic active hepatitis [group 2], 20 with mixed bilharziasis and cirrhosis [group 3] and 15 with active cirrhosis [group 4]. Both parameters were significantly elevated in all the patients groups. In groups 3 and 4, they were. significantly higher than in groups 1 and 2. Although no significant differences were found between groups 1 and 2 or between groups 3 and 4, the study of one way analysis of variance [ANOVA] revealed that they had significantly high F-ratios that were not preceded except by serum albumin, reflecting their high ability to differentiate between our groups of patients. HBc Ab and Anti-HCV Ab were the only hepatitis markers with significantly elevated incidences of positivity found in groups 2, 3 and 4 denoting that HBV and HCV are important causes of chronic liver diseases in Egypt. We recommend serum Lam PI and PIIIP to be estimated repeatedly in every child with liver disease. Greater and persistent efforts are needed to combat bilharziasis, HBV and HCV

biological significance of laminin and fibronectin in bladder cancer

Laminin [LnP1] and fibronectin [Fn] were estimated in the sera of 27 cases with bladder carcinoma of different histopathological types: Papillary superficial transitional cell carcinoma [TCC] [nine cases], invasive TCC [12 cases] and squamous cell carcinoma [six cases]. Only 18 patients were followed up after treatment. Ten normal individuals and 12 cases suffering from benign bladder lesions were included in the study for comparison. Serum LnP1 was significantly higher compared with controls in all groups except in the benign bladder lesions group. It was noticed that a progressive increase in the mean value of serum LnP1 accompanied a change in the grade of the disease. Tissue detection for LnP1 by immunoperoxidase revealed a continuous intact basement membrane [BM]. BM loss was directly proportional to the grade of bladder carcinoma. Serum Fn values revealed no significant difference compared with controls in all the studied groups. Fn immunoperoxidase staining showed negative or weak results in all the studied groups. Serum LnP1 may be a diagnostic and prognostic parameter in TCC after the exclusion of other diseases that increase its expression. It may also be used for monitoring and detecting the recurrence

Serum laminin, hyaluronan, and procollagen Ill: diagnostic and prognostic markers in liver cirrhosis

This work was carried out on 30 patients with liver cirrhosis and ten normal subjects, age and sex matched, served as controls. The patients were classified according the Child and Turcotte [Child A: n=16 Child B: n=6. Child C: n=8]. Serum laminin, hyaluronan, and type III procollagen were determined to evaluate their role as diagnostic and prognostic markers in inducing major severe complications in liver cirrhosis. The serum laminin, hyaluronan, and type III procollagen were significantly elevated in liver cirrhosis patients compared to controls and this elevation increased with more advanced Child stage. Also there was a positive correlation, between these parameters and esophageal varices and the occurrence of major complications in liver cirrhosis. We can concluded that serum laminin, hyaluronan and procollagen III are useful, and noninvasive parameters in patients with liver cirrhosis and as clinically important markers in addition to Child classification for deterioration of liver cirrhosis

Hepatic structural glycoprotein metabolism in liver cirrhosis and its correlation with different disease parameters

This study was conducted on 39 patients diagnosed as liver cirrhosis and 20 age and sex matched controls. Twenty-six patients had clinical and/or sonographic evidence of ascites, but only 22 could be subjected to sampling of their ascites. Serum laminin [LPI] was estimated in all patients and controls, while ascitic fluid LPI was assessed only in 22 samples. Mean value +/- SD of serum LPI in patients [2.36 +/- 0.8] was significantly higher than control group [1.47 +/- 0.25]. Ascitic fluid laminin showed a significant correlation to serum laminin. A ratio of ascitic fluid LPI/serum LPI was calculated with a mean +/- SD of 0.944 +/- 0.45. Mean value of +/- SD of serum LPI in patients with history of gastrointestinal [GI] bleeding [2.69 +/- 1.13] was significantly higher than in patients with no such history [2 +/- 0.92]. Serum LPI was also significantly correlated to the quantitative reduction of hepatic right and left robe spans as measured by ultrasonography. The results suggested that serum LPI values were correlated with the degree of hepatic fibrosis. The study provided a potential new risk factor for GI bleeding from esophageal varices. The study also provided, for the first time, the ratio of ascitic fluid LPI/serum LPI in patients with liver cirrhosis

Procollagen III peptide and laminin as serum markers of diabetic retinopathy

Sixty two diabetic patients [44 NIDDM and 18 IDDM patients] and twenty control subjects were subjected to estimation of serum fructosamine, serum procollagen III peptide [PIIlP] and serum laminin. Patients were classified according to fundus examination into either those without retinopathy or with background [BGR] or with proliferative [PR] retinopathy. Serum fructosamine was elevated in all diabetics. PIIlP was significantly higher in patients with PR than controls or patients with BGR. Elevation of serum laminin was noticed in all diabetics than controls except in IDDM patients without retinopathy but the difference between patients with and without retinopathy was not significant. Both serum level of laminin and PIIlP were found significantly elevated in NIDDM who received insulin. There was significant correlation between serum PIIlP and laminin with the duration of diabetes and with each other. There was no correlation between either PIIlP and laminin and fructosamine. As a conclusion, estimation of serum PIIP may be of value as a marker of diabetic retinopathy. Serum laminin level does not help to differentiate between diabetic patients with and without retinopathy. Insulin treatment increases the levels of both serum laminin and PIIIP

Serum procollagen III and serum laminin P1 in childhood acute rheumatic fever

The study included 35 cases of acute rheumatic fever [21 cases with carditis, 6 cases with arthritis and 8 cases with carditis and arthritis], aged 5-15 years and 15 healthy age matchable children as controls. Both cases and controls were subjected to thorough history, complete clinical examination, complete blood count, E.S.R. determination, estimation of antistreptolysin 0 titre, plain X-ray chest and heart, and determination of serum procollagen III and serum laminin P1. All the cases as well as the different subgroups studied of rheumatic fever had significantly lower serum procollagen III and significantly higher serum laminin P1 than controls. Serum laminin P1 was significantly higher in cases with cardiomegally than cases without cardiomegally. Cases with double mitral lesions showed significantly higher serum laminin P1 than cases with isolated mitral regurge. Serum laminin P1 was a sensitive indicator in carditis [95.2%], in carditis with arthritis [62.5%], and in arthritis [50%]

Studies of laminin in the liver and sera of schistosomal hepatic fibrosis

The distribution of the high molecular weight glycoprotein, laminin in the liver and estimation of serum laminin in 32 patients infected with Schistosoma mansoni have been studied by indirect immunofluorescence using type specific antibodies and by radioimmunoassay. Serum laminin levels in our assays were significantly correlated with histological scores of fibrosis. Increases in laminin concentrations were positively correlated with the extent of fibrotic transition of the liver

Two-site immunoassays for the measurement of serum laminin: correlation with breast cancer staging and presence of auto-antibodies

Binding to and destruction of basement membrane (BM) are necessary steps for cancer cells to extravasate and metastasize. Serum levels of released BM components may correlate with the staging of human cancers or with inflammatory disorders. Furthermore, released material may also induce autoantibodies. Since Iaminin, an 800-kDa glycoprotein, is present in the extracellular matrix, serum laminin levels may be markers of BM injury. A two-site enzyme immunoassay and a radioimmunoassay were developed to test sera from patients with breast cancer or systemic lupus erythematosus (SLE). A significant difference in laminin concentrations was demonstrated between early (T0-T2) and advanced (T3-T4) tumors (P = 0.001). However, specimens from SLE patients did not differ in laminin concentration from normal individuals and no correlation was observed between laminin levels and anti-laminin auto-antibody titers. These results suggest that serum laminin levels are useful markers of BM damage and could be of prognostic value in cancer