Correlation Of Soluble CD44 Isoform,HA And Thyroid Hormone To Liver Fibrosis

Object:Liver fibrosis results from chronic damage to the liver. Assessment of liver fibrosis as well as monitoring of patients with chronic liver disease over time remains a major clinical challenge. Although liver biopsy is still considered the gold standard for assessing liver fibrosis, it is an invasive technique associated with sampling error, interobserver variability and potential complications. Therefore, noninvasive reliable assessment as serum biomarker for liver damage and for treatment response would be highly desirable to quantify the magnitude of liver fibrosis in humans. CD44 is a cell surface hyaluronate receptor and cell adhesion molecule which involves in HA degradation. Soluble form of CD44 in the circulation which include standard CD44s and splicing variant isoforms CD44v. Corelation of HA,soluble CD44 isoform sCD44s and sCD44v to liver fibrosis were investigated and thyroid hormone level was evaluated in the patients with liver fibrosis along with non liver disease patient and healthy population.Methods:80 patients with chronic hapotitis B (CHB) were grouped based on liver biopsy and inflammation, 15 patients without liver disease as control group and 15 persons as healthy control. Serum sCD44s and sCD44v6 were detected by ELISA, hyaluronic acid and thyroid hormons by chemiluminescence method. The ratios of sCD44s/HA,sCD44v6/HA were calculated. The relationship between biomarkers and fibrosis as well as inflammation stages was analysed by Mann-Whitney test and Spearman correlation analysis.The diagnostic significance of sCD44s and sCD44v6 was evaluated based on ROC curve against pathological biopsy.Results:80 patients with chronic hapotitis B (CHB) were grouped based on liver biopsy and inflammation, in which, 11 cases were fallen into level S0,14 cases into S1,16 cases into S2,17 cases into S3, 22 cases into S4; 12 cases into G1,16 cases into G2,41 cases into G3,11 cases into G4. 15 patients without liver disease as disease control group and 15 persons as healthy control group.1. Analysis of sCD44s,sCD44v6,HA,sCD44s/HA,sCD44v6/HA in CHB group.The values of sCD44s(858 ng/ml),HA(71.3 ng/ml)of CHB group were significantly higher than healthy control group(sCD44s 465 ng/ml,HA 18.8 ng/ml) and disease control group (sCD44s 418 ng/ml,HA 20.4 ng/ml)(P<0.01);the levels of sCD44s/HA(10.68),sCD44v6/HA(0.7) were tested in CHB group were much lower than healthy control group(sCD44s/HA 23.7,sCD44v6/HA 2.72) and disease control group(sCD44s/HA 19.89,sCD44v6/HA 2.2)(P<0.01);the levels of sCD44v6 in CHB group(42 ng/ml),healthy control group(51 ng/ml)and disease control group(46 ng/ml)had no significant diffrences.2. The relationship between sCD44s,sCD44v6,HA,sCD44s/HA,sCD44v6/HA and fibrosis stages.sCD44s(889 ng/ml),HA(81.4 ng/ml)of fibrosis group were much higher than no fibrosis group (sCD44s 465 ng/ml,HA 20.6 ng/ml),(P<0.01); sCD44v6(37 ng/ml),sCD44s/HA(10.71),sCD44v6/HA(0.56)of fibrosis group were much lower than (sCD44v6 54 ng/ml,sCD44s/HA 19.89,sCD44v6/HA 2.25)(P<0.05).sCD44s,HA and fibrosis stages showed positive correlation;and sCD44v6,sCD44v6/HA and fibrosis stages showed negtive correlation;while there was no correlation between sCD44s/HA and fibrosis stages.3. The relationship between sCD44s,sCD44v6,HA,sCD44s/HA,sCD44v6/HA and inflammation stages.sCD44s(858 ng/ml),HA(71.3 ng/ml)of inflammation group were much higher than (sCD44s 442 ng/ml,HA 19.6 ng/ml),(P<0.01);sCD44s/HA(10.68),sCD44v6/HA ( 0.7 ) of inflammation group were much lower than noninflammation group(sCD44s/HA 20.9,sCD44v6/HA 2.50),(P<0.01).there was no significant differences between sCD44v6 in inflammation group and in noninflammation group,(P>0.05).sCD44s,HA and inflammation stages showed positive correlation;and sCD44v6,sCD44v6/HA and inflammation stages showed negtive correlation;while there was no correlation between sCD44s/HA and inflammation stages.4.Evaluation of liver fibrosis by sCD44s,HA,sCD44s/HA,sCD44v6/HA .The ROC curves of the biomarkers tested liver fibrosis were sCD44s( 0.8696 ) > HA ( 0.6252 ) > sCD44s/HA ( 0.5026 ) > sCD44v6/HA(0.2971),respectively.There were no statistical significant in sCD44v6 of CHB group, healthy control group and disease control group,which was not mentioned. According sCD44s>732 ng/ml that is the critical value of dignosing liver fibrosis,the sensitivity and the specificity of sCD44s were 82.61% ,81.82%,respectively.The positive likelihood ratio was 4.54 and the negative likelihood ratio was 0.21.According sCD44s>849 ng/ml that is the critical value of dignosing hepatocirrhosis, the sensitivity and the specificity of sCD44s were 86.36% ,70.51%, respectively.The positive likelihood ratio was 2.93 and the negative likelihood ratio was 0.1934.The AUC of dignosing hepatocirrhosis was 0.8214.5. Evaluation of liver fibrosis by thyroid hormone .Thyroid hormone levelshowed no significant differeces in CHB group(TT₃ 1.88 nmol/L,TT₄ 89.57 nmol/L,FT₃ 4.50 pmol/L,FT₄ 15.73 pmol/L, TSH 1.54 mIU/L),healthy control group(TT₃ 1.94 nmol/L,TT₄ 95.56 nmol/L,FT₃ 4.31 pmol/L,FT₄ 15.47 pmol/L,TSH 1.65 mIU/L)and disease control group (TT₃ 1.92 nmol/L,TT₄ 93.17 nmol/L,FT₃ 4.40 pmol/L,FT₄ 14.95 pmol/L,TSH 1.36 mIU/L)(P>0.05); FT₄ of fibrosis group(15.73 pmol/L) was higher than in no fibrosis group(FT₄ 14.17 pmol/L,P<0.05).There were no differnces in TT₃(1.85 nmol/L),TT₄(90.99 nmol/L),FT₃(4.47 pmol/L),TSH(1.55 mIU/L) of fibrosis group and no fibrosis group(TT₃ 1.91 nmol/L,TT₄ 91.89 nmol/L,FT₃ 4.31 pmol/L,TSH 1.58 mIU/L)(P>0.05).FT₄ of inflammation group(15.73 pmol/L) was higher than in noninflammation group(FT₄ 14.04 pmol/L,P<0.05).There were no significant differnces in TT₃(1.85 nmol/L),TT₄(89.58 nmol/L),FT₃(4.50 pmol/L),TSH(1.55 mIU/L) of inflammation group and noninflammation group(TT₃ 1.92 nmol/L,TT₄ 96.52 nmol/L,FT₃ 4.36 pmol/L,TSH 1.58 mIU/L)(P>0.05).There was no correlation of TT₃,TT₄,FT₃,FT₄,TSH and fibrosis stages as well as inflammation stages, while TT₄,FT₄ and fibrosis as well as inflammation stages showed positive correlation.Conclusion:1. As a new biomarker in diagnosing liver fibrosis sCD44s is sensitive and specific,which is much better than conventional HA testing.sCD44s and fibrosis stages as well as inflammation stages showed positive correlation.sCD44s/HA and fibrosis stages as well as inflammation stages showed no correlation.But sCD44v6/HA and fibrosis stages as well as inflammation stages showed negtive correlation.2. thyroid hormone is not correlated to liver fibrosis.