Serum profiles of extracellualr matrix degradation inhibitors across the stages of liver fibrosis in chronic hepatitis C patients

Tissue inhibitor metalloproteinase-1 [TIMP-1] and alpha-2 macroglobulin [AMG] are extracellular matrix degeneration inhibitors that have been demonstrated to increase with liver fibrosis. However, date are lacking regarding their patterns of change. This study analyses their detailed serum profile across liver fibrosis stages in chronic hepatitis C [CHC]. Serum TIMP-1 and AMG measurements were evaluated for 78 adult male CHC patients versus liver fibrosis [F] stages [METAVIR F0-F4]. The performance characteristics for discrimination of sequential [close stages], significant [F >/= 2], and advanced [F >/= 3] fibrosis were assessed. Both TIMP-1 and AMG correlated significantly with fibrosis [r=0.31, p=0.005; r=0.37, p=0.001, respectively], but failed to discriminate sequential stages. For discrimination of significant fibrosis, the areas under receiver operating characteristics curves were small [0.59 and 0.57, respectively]. T a cut-off value of 743 ng/ml, TIMP-1 showed a 100% specificity [with 17.6% sensitivity], while at a cut-off of 3 gm/l, AMG showed 73.5% sensitivity [with 36.4% specificity]. A similarly modest discrimination was noted for advanced fibrosis. Interestingly, AMG showed an early rise with significantly higher values in F0 compared with healthy controls [3.6 +/- 1.1 vs. 1.8 +/- 0.6, respectively]. Neither TIMP-1 nor AMG could discriminate the sequential stages of fibrosis. Their modest performances for discrimination of significant and advanced fibrosis are related to the wide normal range f TIMP-1 and the early rise of AMG. A longitudinal monitoring would give a better understanding of their true changes, and examine whether patients having high AMG levels at F0 would be fast fibrosers or respond differently to therapy

Serum cystatin C in advanced liver cirrhosis and different stages of the hepatorenal syndrome

The hepatorenal syndrome [HRS] is classified into two types [HRS-2 and HRS-1] based on mild or high serum creatinine elevations. Although it has been identified as an early marker of renal dysfunction, data are lacking about cystatin C across the wide range of renal changes in end-stage liver disease. This study investigates serum cystatin C and creatinine in patients with advanced liver cirrhosis and classic HRS throughout its whole spectrum. Serum cystatin C immunonephelometric measurements were obtained from 65 Child-Pugh C patients: 32 with normal creatinine, 17 with HRS-2 and 16 with HRS-1. The glomerular filtration rate [GFR] was estimated according to modification of diet in renal disease [MDRD] and the Hoek formulae [creatinine- and cystatin C-based, respectively] with staging of renal dysfunction severity into an increasing order from 1 to 5. Early HRS was identified by the raised cystatin C in 56.3% of patients having normal creatinine. Cystatin C correlated significantly with creatinine in HRS-2 [r = 0.74; p < 0.001] and showed a significantly lower multiplication ratio [folds of rise] compared to creatinine in HRS-1 patients [p < 0.01]. There was no satisfactory agreement between MDRD and Hoek GFR staging [k = 0.29]. The 'early' HRS identified by a rise in cystatin C in cases with advanced cirrhosis was found to be common and can be added to the already classified two types, as type-3 HRS. Compared to creatinine, cystatin C provides no better information in HRS-2, and underestimates the renal deterioration in HRS-1. Further studies are required to determine the course of the early HRS