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AIM:Noninvasive diagnosis of hepatic fibrosis has becomethe focus because of the limited biopsy,especially in thesurveillance of treatment and in screening hepatic fibrosis.Recently,regulaton/elements involved in liver fibrosis,suchas platelet derived growth factor-BB (PDGF-BB),transforminggrowth factor-β_1 (TGF-β_1),matrix metalloproteinase-1 (MMP-1),and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1),have been studied extensively.To determine whetherthese factors or enzymes could be used as the indices forthe diagnosis of hepatic fibrosis,we investigated them bymeans of receiver operating characteristic (ROC) curve.METHODS:Serum samples from sixty patients with chronicviral hepatitis B and twenty healthy blood donors wereassayed to determine the level of PDGF-BB,TGF-β_1,MMP-1,and TIMP-1 with ELISA,and HA,PCⅢ,C-IV,and LNlevel with RIA.The message RNA (mRNA) expression ofTIMP-1 and MMP-1 in peripheral blood mononuclear cells(PBMCs) was detected by RT-PCR and Northern blothybridization.Liver biopsy was performed in all patients.The biopsy samples were histopathologically examined.Thetrial was double-blind controlled.RESULTS:The serum level of PDGF-BB,TIMP-1,the ratioof TIMP-1 and MMP-1 (TIMP-1/MMP-1),mRNA expressionof TIMP-1 (TIMP-1mRNA),and the ratio of TIMP-1mRNAand MMP-1mRNA (TIMP-1mRNA/MMP-1mRNA) in patientswas significantly higher than those in the healthy blooddonors (t=2.514-11.435,P=0.000-0.016).The serum levelof PDGF-BB,TIMP-1,TIMP-1/MMP-1,and TIMP-1mRNA waspositively correlated with fibrosis stage and inflammationgrade (r=0.239-0.565,P=0.000-0.033),while the serumlevel of MMP-1 was negatively correlated with fibrosis stageand inflammation grade,and TIMP-1mRNA/MMP-1mRNAwas positively correlated with inflammation grade.Throughthe analysis by ROC curve,serum PDGF-BB was the mostvaluable marker,and its sensitivity was the highest amongthe nine indices.The markers with the highest specificitywere TIMP-1mRNA and TIMP-1mRNA/MMP-1mRNA inPBMCs.The area under the curve (AUC) of PDGF-BB,TIMP-1mRNA,TIMP-1mRNA/MMP-1mRNA,TIMP-1/MMP-1,HA, PCⅢ,TIMP-1,C-IV,and LN was 0.985,0.876,0.792,0.748,0.728,0.727,0.726,0.583,and 0.463,respectively.Thesensitivity and the specificity in the parallel test was 99.0%and 95.0% when serum PDGF-BB,TIMP-1mRNA and TIMP-1mRNA/MMP-1mRNA was detected simultaneously.CONCLUSION:Serum level of PDGF-BB,TIMP-1mRNA,TIMP-1mRNA/MMP-1mRNA in PBMCs,and serum level ofTIMP-1 and TIMP-1/MMP-1 can be used as the indices forthe diagnosis of hepatic fibrosis,but the former three aremore useful.The combination of serum PDGF-BB,TIMP-1mRNA and TIMP-1mRNA/MMP-1mRNA in PBMCs is evenmore efficient in screening liver fibrosis.
AIM: Noninvasive diagnosis of hepatic fibrosis has become the focus because of the limited biopsy, especially in thesurveillance of treatment and in screening hepatic fibrosis. Rescently, regulaton / elements involved in liver fibrosis, suchas platelet derived growth factor-BB (PDGF-BB) transforming growth factor-β_1 (TGF-β_1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP- 1), have been studied extensively. indices forthe diagnosis of hepatic fibrosis, we examined them bymeans of receiver operating characteristic (ROC) curve. METHODS: Serum samples from sixty patients with chronic viral liver B and twenty healthy blood donors were all assigned to determine the level of PDGF-BB, TGF- MMP-1, and TIMP-1 with ELISA, and HA, PCIII, C-IV, and LNlevel with RIA. The message RNA (mRNA) expression ofTIMP- 1 and MMP- 1 in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR and Northern bloth The levels of PDGF-BB, TIMP-1, the ratio of TIMP-1 and MMP-1 (TIMP- 1 / MMP-1), mRNA expressionof TIMP-1 (TIMP-1 mRNA), and the ratio of TIMP-1 mRNA and MMP-1 mRNA in patientswas significantly higher than those in the healthy blood donors (t = 2.514-11.435, P = 0.000-0.016). The serum level of PDGF-BB, TIMP-1, TIMP- 1 / MMP- 1, and TIMP- 1 mRNA were positively correlated with fibrosis stage and inflammationgrade (r = 0.239-0.565, 0.000-0.033), while the serum level of MMP-1 was negatively correlated with fibrosis stage and inflammation grade, and TIMP-1 mRNA / MMP-1 mRNA was positively correlated with inflammation grade. Throughthe analysis by ROC curve, serum PDGF-BB was the mostvaluable marker, and its sensitivity was the highest among the nine indices. markers with the highest specificity we TIMP-1 mRNA and TIMP-1 mRNA / MMP-1 mRNA in PBMCs. The area undeTIMP-1 mRNA, TIMP-1 / MMP-1, HA, PCIII, TIMP-1, C-IV, and LN was 0.985, 0.876, 0.792,0.748,0.728,0.727,0.726,0.583, and 0.463, respectively. The sensitivity and the specificity in the parallel test was 99.0% and 95.0% when serum PDGF-BB, TIMP-1 mRNA and TIMP-1 mRNA / MMP- simultaneously.CONCLUSION: Serum level of PDGF-BB, TIMP-1 mRNA, TIMP-1 mRNA / MMP-1 mRNA in PBMCs, and serum level of TIMP-1 and TIMP- 1 / MMP-1 can be used as the indices forthe diagnosis of hepatic fibrosis , but the former three are useful useful. combination of serum PDGF-BB, TIMP-1 mRNA and TIMP-1 mRNA / MMP-1 mRNA in PBMCs is even more efficient in screening liver fibrosis.