Diagnostic value of serum fibrosis markers [hyaluronic acid and matrix metaloproteinase-2] as a marker of hepatic fibrosis

Several biochemical markers have shown promise for the detection of advanced fibrosis and cirrhosis. The aim of the present work is to study the diagnostic accuracy of serum hyaluronic acid [SHA] and matrix metaloproteinase-2 [MMP-2] as indicators for the stages of hepatic fibrosis, and to correlate the liver pathology and liver function tests with serum fibrosis markers. Sixty treatment naive patients with chronic liver disease [30 with chronic hepatitis C [CHC] with or without HBV and 30 patients with cirrhosis]. The patients were divided according to Metavir classification of liver biopsy into 3 groups. Group 1 with normal biopsy [12 patients], group 2 -25 patients with mild fibrotic changes [stage 1-2] and group 3 of 23 patients with severe fibrosis [stage 3-4]. SHA level was significantly higher in patients with severe fibrosis than patients with mild or no hepatic fibrosis [378.7 +/- 147.5, 226.2 +/- 123.7and 85.3 +/- 52.2 pg/ml]. [P<0.0001]. MMP-2 was also significantly higher in severe fibrosis [group 3] than gr2 or gr1 [1196.2 +/- 119.5, 918.1 +/- 175.8 and 841.1 +/- 224.5 pg/ml] respectively [P<0.001]. SHA and MMP-2 were not correlated to age, S bilirubin, AST, ALT or spleen size. Group 3 was correlated significantly to the SHA and MMP, platelet count, S albumin and liver size but not correlated to AST, ALT, S. bilirubin or spleen size. The specificity of fibrosis markers SHA and MMP-2 in prediction of severe fibrosis were 94.4% and 90.0% respectively and the sensitivity were higher to SHA 90% than MMP-2 80% but not a predictor of mild or normal biopsy. The cut of value of SHA, MMP-2, platelet count and prothrombin time [PT], in diagnosis of severe fibrosis were 294.84 pg/ml., 1003 pg/ml., 115.084/cmm, 72.116% respectively. Measurement of SHA and MMP-2 can be used to differentiate cirrhotic from non-cirrhotic patient and can be regarded as a useful test in the diagnosis of liver cirrhosis

Proinflammatory cytokines [IL-12 and IL-18] in immune rheumatic diseases: relation with disease activity and autoantibodies production

lnterleukin-18 [IL-18] and its inducer IL-12 have multiple biological activities that are important in generating Th1 responses and inflammatory tissue damage. We investigated serum concentration of the novel pro-inflammatory Th1 cytokine; IL-18, and its inducer IL-12 in patients with immune rheumatic diseases. Group I comprised 32 patients of systemic lupus erythmatosus [SLE], Group II comprised 36 patients of rheumatoid arthritis [RA]. Group III comprised 9 patients [2 patients of Behcet, 2 patients of Dermatomyositis, 2 patients of Sicca syndrome, one patient of Scleroderma, and 2 patients of Mixed connective tissue disease]. Group IV is a control group consists of 21 sex and age matched healthy subjects and correlated their levels with autoantibody concentration [ANA and ds-DNA], clinical grades and SLE disease activity index [SLEDAI]. Serum IL-18, IL-12 ,ANA and ds-DNA were measured by enzyme immune sorbent assay. IL-18, IL-12 and ANA were significantly higher in the three studied groups than in the control group [IL-18; P<0.001 in the three groups, IL-12; P=0.019, P=0.002, and P= 0.006, and ANA; PO.001, P=0.002,and P=0.006, respectively].ds-DNA was significantly higher in SLE patients than in control group [P<0.001].There were significant positive correlations between; A] levels of IL-18,and both ANA and ds-DNA in SLE patient [r=0.41,P=0.001, r= 0.58 and P=0.001 respectively]; and B] IL-18 and ANA in both RA and group III patients [r= 0.32, P=0.005,r=0.61 and P= 0.022 respectively]. Also, there were significant positive correlation between the levels of IL-18 and clinical grades of the three groups [r=0.60, P=0.001, r=0.79, P=0.001, r=0.78 and P= 0.001 respectively]. In SLE patients ,IL-18 concentration shows significant positive correlation with SLEDAI score [r= 0.76 ,P=0.001]. In conclusion, the elevation of proinflammatory cytokines [IL-18 and IL-12] may trigger the inflammatory process in immune rheumatic diseases and IL-18 is correlated with disease activity

impact of immunoglobulin E serum levels on clinical presentation and immunological status in graves' hyperthyroidism

There is growing evidence pointing to the involvement of IgE in the pathogenesis of Graves' disease. Despite this evidence, the diagnostic significance of IgE in Graves' hyperthyroidism is still not established. Therefore, forty-six patients with hyperthyroid Graves' disease were studied together with twenty patients with toxic nodular goiter and 25 age and sex matched healthy subjects. Quantitative estimation of IgE. antithyroid perioxidase [Anti-TPO] and antithyroglobulin [Anti-Tg] were analyzed by sandwich ELISA. Peripheral blood CD3+, CD4+ and CD8+ were analyzed by direct immunoflourescence. Natural killer activity was measured by a standard 4-hour Cr[51] releasing assay. The data of the present study revealed significant elevation of IgE, Anti-TPO and Anti-Tg antibodies in hyperthyroid Graves' disease [196.54 +/- 199.4 IU/ml, 219.3 +/- 66.41 lU/ml and 278.8 +/- 86.51 IU/ml respectively] than in toxic nodular goiter [49.4 +/- 51.97 IU/ml, 57.15 +/- 13.29 IU/ml and 116.55 +/- 67.94 IU/ml respectively] or control subjects [44.32 +/- 43.4 IU/ml. 50.32 +/- 10.07 IU/ml and 94.8 +/- 10.79 IU/ml respectively]. Hyperthyroid Graves' patients with IgE elevation had increased incidence of ophthalmopathy, increased clinical and biochemical severity of the disease and increased thyroid autoantibodies titres together with reduced natural killer activity in comparison to patients with normal lgE serum levels. Graves' patients with clinically evident ophthalmopathy had significantly higher levels of IgE, Anti-TPO and Anti-Tg antibodies besides reduced natural killer activity than those without ophthalmopathy. From this study, it is concluded that IgE determination in hyperthyroid Graves' disease could define a subgroup of patients with altered clinical and immunological profiles. Hyperthyroid Graves' patients with ophthalmopathy have more marked immunological changes despite nonsignificant differences in clinical or biochemical severity of the disease in comparison to patients without ophthalmopathy