Serum hyaluronan and collagen IV as non-invasive markers of liver fibrosis in patients from an endemic area for schistosomiasis mansoni: a field-based study in Brazil

Non-invasive markers of fibrosis have been used to diagnose liver fibrosis in a variety of diseases. Hyaluronic acid (HA) and collagen IV (C-IV) levels were measured in the sera of patients from an endemic area for schistosomiasis in Brazil to diagnose and to rank the intensity of liver fibrosis. Seventy-nine adult patients with schistosomiasis, in the age range of 21-82 years (49 ± 13.4) were submitted to clinical and ultrasonographic examinations. Ultrasound was employed to diagnose and categorise liver fibrosis according to World Health Organization patterns. Serum HA and C-IV levels were measured using commercial ELISA kits. Ultrasound revealed six patients with intense liver fibrosis, 21 with moderate, 23 with light and 29 without. Serum HA was able to separate individuals with fibrosis from those without (p < 0.001) and light from intense fibrosis (p = 0.029), but C-IV was not (p = 0.692). The HA diagnostic accuracy for fibrosis was 0.89. The 115.4 ng/mL cut-off level diagnosed patients with fibrosis (sensitivity 0.98, specificity 0.64). HA correlated positively with portal hypertension. Periportal fibrosis (subjective evaluation), age and collateral circulation predicted HA increase. In conclusion, we propose that serum HA can be used to identify patients with liver fibrosis in an endemic area for schistosomiasis mansoni in Brazil.

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.

The Diagnostic Value of Serum Hyaluronic Acid, 7S Domain of Type IV Collagen and AST/ALT Ratio as Markers of Hepatic Fibrosis in Chronic Hepatitis B and Cirrhosis Patients / 대한간학회지

BACKGROUND/AIMS: The prognosis of chronic liver disease is closely related to the development of hepatic fibrosis. Liver biopsy is the gold standard method to assess inflammatory activity and fibrosis stage, but this is associated with morbidity and mortality. This study aimed to evaluate the diagnostic value of serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis. METHODS: This study included 100 patients with chronic hepatitis B and cirrhosis. Liver biopsy and histopathologic classification were done. Serum hyaluronic acid and 7S domain of type IV collagen were measured by one step sandwich binding protein assay and radioimmunoassay using polyclonal antibody to 7S domain of type IV collagen, respectively. RESULTS: The serum concentrations of hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio in the cirrhosis group (139 +/- 98.4 ng/mL, 6.9 +/- 3.5 ng/mL, 1.6 +/- 1.5) were significantly higher (p<0.01) than those in the normal and fatty liver group (20.2 +/- 12.5 ng/mL, 3.5 +/- 0.5 ng/mL, 0.7 +/- 0.3), mild hepatitis group (32.3 +/- 52.7 ng/mL, 3.9 +/- 1.4 ng/mL, 0.7 +/- 0.4), and moderate to severe hepatitis group (68.2 +/- 72.3 ng/mL, 5.3 +/- 2.4 ng/mL, 0.8 +/- 0.4). At the cutoff value of 77 ng/mL for hyaluronic acid and 6.3 ng/mL for 7S domain of type IV collagen and 0.62 for AST/ALT ratio, the sensitivities were 81.8%, 63.6%, 90.9% and specificities were 87.3%, 88.6%, 53.1% for discriminating cirrhosis (fibrosis score: 4) from the mild to severe fibrosis (fibrosis score: 0-3). CONCLUSIONS: Serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio measurement may be clinically useful as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis.