Usefulness of collagen type IV in the detection of significant liver fibrosis in nonalcoholic fatty liver disease.

INTRODUCTION/AIMS: Liver fibrosis assessment is a key issue in the evaluation of nonalcoholic fatty liver disease (NAFLD) patients. In the present study, we aimed to validate a noninvasive marker panel to assess significant and advanced fibrosis in these patients. METHOD: 126 biopsy-proven NAFLD patients were included. NAFLD diagnosis was based on histological criteria. Fibrosis stages were determined according to NASH-Clinical Research Network criteria. Clinical and laboratorial data were collected during the interval of three months before or after liver biopsy. Histological fibrosis stages were classified as significant fibrosis (F2-F4) and advanced fibrosis (F3-F4). Five serum biomarkers [hyaluronic acid (HA), collagen type IV (cIV), procollagen type III (PC III), laminin (LN) and cholylglycine (CG)] were assessed by chemiluminescence immunoassays. RESULTS: Most patients were female (61.61%), mean age: 55.7 ±â€¯9.13 years old and mean BMI was 32.1 ±â€¯5.9 kg/m2. Prevalence of diabetes, dyslipidemia, arterial hypertension, and metabolic syndrome was 68.75%, 82.29%, 63.54% and 81.05%, respectively. Patients with cIV above 30 ng/mL had a 5.57-times (IC: 1.86-16.69) the chance of having significant fibrosis and 7.61-times (IC: 2.27-25.54) the chance of having advanced fibrosis versus patients with values below 30 ng/mL. HA, PC III, LN and CG did not detect the presence of significant and advanced fibrosis. The AUROC of clV for detection of significant (0.718) and advanced fibrosis (0.791) was better than that of other serum biomarkers. CONCLUSION: Type 4 collagen could predict the presence of significant and advanced fibrosis in NAFLD patients and it would be a useful tool in routine clinical practice.

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%, 83.3%, 90.6%, 73.5%, 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%, 80.0%, 87.2%, 60.0%, 3.59%, 0.35% and 74.7, respectively. Combinations of HA and LN by serial tests showed a perfect specificity and PPV of 100%, at the same time sensitivity declined to 63.2% and LR+ increased to 18.9, while parallel tests revealed a good sensitivity of 94.7%, NPV to 86.4%, 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.

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.

Is there a place for serum laminin determination in patients with liver disease and cancer?

Laminin is a glycoprotein which has an important role in the mechanism of fibrogenesis and is, thus, related to hepatic fibrosis in addition to presenting increased levels in several types of neoplasias. However, its determination is not routinely considered in the study of hepatic fibrosis. In this review, the authors critically comment on the role of this glycoprotein compared to other markers of fibrosis through non-invasive procedures (Fibroscan). They also consider its clinical investigational potential and believe that the continuation of these investigations might contribute to a better understanding of the fibrogenic mechanism, which could in turn either lead to the identification of patients at risk of developing fibrosis non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) or at least be used as an indicator for hepatic biopsy in such patients. Finally, the authors believe that serum laminin determination might contribute to the diagnosis of epithelial tumor metastasis and peritoneal carcinomatosis.

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% 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.

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 microg/ml, mean +/- SD, P < 0.05) and ascites (2.8 +/- 0.5 vs 1.6 +/- 0.4 microg/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 microg/ml showed 100% sensitivity and 73% 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.

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.

High serum laminin and type IV collagen levels in schistosomiasis mansoni.

BACKGROUND: Fibrosis is the process of excessive deposition of collagen and other extra cellular matrix components and large amounts of these components have been shown in periovular schistosomal granulomas, especially in the liver. Laminin and type IV collagen have been investigated in various hepatic disorders but their accuracy in fibrosis detection and in the evaluation of its progression in schistosomiasis have not been fully explained. AIM: To measure the serum levels of two markers of fibrosis, laminin and type IV collagen in schistosomiasis. PATIENTS AND METHODS: Sixty-four patients with different clinical forms of schistosomiasis mansoni: intestinal (group I), hepatointestinal (group II), compensated (group III) and decompensated hepatosplenic (group IV) and 18 healthy volunteers were included. RESULTS: Serum type IV collagen and laminin levels were significantly increased in patients compared to controls. At about clinical forms, serum type IV collagen was increased in groups II and IV, compared to controls and was significantly higher in group IV than in group I. Serum laminin was significantly increased in groups II, III and IV and was significantly higher in group IV than in group II. Serum type IV collagen was closely correlated with serum laminin in groups II and IV. CONCLUSIONS: Connective tissue marker levels did not correlate with periportal thickness. In schistosomiasis mansoni there is an increase of type IV collagen and laminin levels at the initial stage of the disease, as well as in advanced forms. We also suggest that these markers may be a useful predictor of disease progression.

[Increased serum levels of laminin in the experimental cirrhosis induced by carbon tetrachloride]. / Elevação dos níveis séricos de laminina na cirrose hepática induzida pelo tetracloreto de carbono.

BACKGROUND: Serum laminin has been correlated with portal hypertension and sinusoid capillarization in chronic liver diseases. Little is known about its dynamics in liver diseases. AIM: To investigate the levels of serum laminin in experimental cirrhosis induced by carbon tetrachloride, as well as to correlate its level with the degree of hepatic fibrosis and portal hypertension. MATERIAL AND METHODS: Forty-nine albino Wistar rats were studied. Twenty-three were treated with carbon tetrachloride solution at 8% and 16 were kept as controls. Between the 6th and 16th weeks, all animals were sacrificed, submitted to measurement of portal pressure and blood sampling of the femoral veins. Liver fragments were fixed for light microscopic studies. Hepatic fibrosis was classified as perivenular fibrosis, complete and incomplete septal fibrosis and cirrhosis. Determination of laminin concentration was performed by ELISA with an antibody against laminin isolated from Engelbreth-Holm-Swarm tumor. RESULTS: The portal pressure was correlated with the degree of hepatic fibrosis (rs = 0.82; n = 45). Its levels in septal fibrosis (10.8 +/- 1.2 cm H(2)0) and cirrhosis (13.6 +/- 3.1 cm H(2)0) were statistically higher when compared to control (7.9 +/- 1.5 cm H20) and perivenular fibrosis (9.1 +/- 0.8 cm H(2)0) groups. Peripheral blood laminin concentration in cirrhosis (40.0 +/- 18.7 mg/dL) was significantly higher when compared to control (13.8 +/- 12.1 mg/dL), perivenular fibrosis (19.1 +/- 15.5 mg/dL) and septal fibrosis (22.2 +/- 27.0 mg/dL) groups. The circulating laminin was correlated to the degree of hepatic fibrosis (rs = 0.59; n = 49) and to portal pressure (r = 0.29; n = 45). CONCLUSIONS: In the chronic carbon tetrachloride intoxication, laminin levels are better correlated with the development of hepatic fibrosis than with portal hypertension.

[Markers of hepatic fibrogenesis in alcoholic patients]. / Marcadores de fibrogénesis hepática en pacientes alcohólicos.

BACKGROUND: An elevation of serologic markers of hepatic fibrogenesis has been reported in liver diseases of different etiologies. Among these, the N-terminal type III procollagen (P-III-P) and the P1 proteolytic fragment of laminin (P1 laminin) increase in alcoholic liver damage, in proportion to the progression of this condition. AIM: To study serum levels of P-III-P and P1 laminin in asymptomatic alcoholics with and without liver damage and decompensated alcoholic cirrhotics, compared to normal controls. METHODS: Serum P-III-P and laminin levels were measured in asymptomatic alcoholics during detoxification treatment. Liver biopsies were obtained, in order to detect liver damage, which was graded with a numeric score, considering values over 6 as severe damage. Serum fibrogenesis markers were also measured in a group of decompensated alcoholic cirrhotics. RESULTS: P-III-P levels were significantly higher in cirrhotic patients compared to alcoholics with or without liver damage and to normal controls. Laminin was not different between groups. P-III-P did not correlate with histologic score in asymptomatic patients. CONCLUSIONS: In this study P-III-P and P1 laminin were not usefull discriminators of severe liver damage among asymptomatic alcoholics; their levels were found to rise significantly only when liver disease has become clinically evident.

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.

Serum laminin in hepatic schistosomiasis.

Serum laminin levels were measured in patients with chronic hepatic schistosomiasis. A significant increase in the mean serum laminin level was observed in 14 patients with hepatosplenic schistosomiasis (2.57 +/- 0.83 units/ml [standard deviation]) compared to the level in 10 patients with the hepatointestinal form of the disease (1.38 +/- 0.45 units/ml) and in the control group of 10 (1.15 +/- 0.31 units/ml). In the hepatosplenic patients there was a significant direct relation between serum laminin and percutaneous splenic pulp pressure (r = 0.68). However, this relation was not observed with either liver function tests or levels of N-terminal propeptides of type III procollagen. These findings are compatible with an increased production of laminin in hepatosplenic schistosomiasis, which 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 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.

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

1. 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 laminin, an 800-kDa glycoprotein, is present in the extracellular matrix, serum laminin levels may be markers of BM injury. 2. A two-site enzyme immunoassay and a radioimmunoassay were developed to test sera from patients with breast cancer or systemic lupus erythematosus (SLE). 3. 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. 4. These results suggest that serum laminin levels are useful markers of BM damage and could be of prognostic value in cancer.

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

Elevation of laminin and beta-subunit of prolyl 4-hydroxylase in the sera of human subjects with Schistosomiasis mansoni.

Serum levels of several markers for liver fibrosis were measured utilizing three groups of human subjects related with schistosomiasis mansoni in northeast Brazil; (1) 20 Schistosoma mansoni egg-positives, who have never been administered with anti-schistosomal drugs, (2) 29 egg-negative inhabitants in the endemic area of schistosomiasis, and (3) 23 egg-negative Japanese immigrants in the non-endemic area. None of these sera were positive for antibody to the surface antigen of human hepatitis B (HBs) and circulating HBs antigen. There was no significant difference in the serum levels of N-terminal peptide of procollagen type-III between the egg-positive subjects and either of the egg-negative Brazilian or Japanese immigrants, whereas the mean value of serum laminin significantly increased in the egg-positive subjects. A significantly higher concentration of serum immunoreactive beta-subunit of prolyl 4-hydroxylase (IR beta PH) was also observed in the egg-positive subjects only in comparison with that of the egg-negative Brazilian. Serum laminin and IR beta PH concentrations of the egg-positive subjects did not correlate with the absorbance of enzyme-linked immunosorbent assay (ELISA) which utilized crude antigens isolated from schistosome adults or eggs. No significant difference in these two parameters was observed between two subgroups of the egg-negative Brazilian or Japanese immigrants divided according to the serological data by ELISA. These findings suggest that serum laminin and IR beta PH levels are worth further evaluation for their usefulness as the marker for liver fibrosis in schistosomiasis.