Serum markers of liver injury in chronic hepatitis C virus infection

VALVA P; CASCIATO P; MULLEN E; DE MATTEO E; GALDAME O; GALOPPO MC; GADANO A; PRECIADO MV

Boston

Congreso; 61 st annual meeting of the American association for the study of liver diseases; 2010

AASLD

Hepatitis related to Hepatitis C Virus (HCV) seems to be milder in children than in adults. Liver biopsy represents the gold standard for evaluating damage. Developing noninvasive tests that can predict initial disease stage and progression represents growing need. Our aim was to determine the presence of specific serum markers that correlate with liver injury during chronic HCV. Liver biopsies and serum samples at time of biopsy from 22 HCV pediatric [median: 8 ys (1?17 ys)] and 21 adult [median: 51 ys (28-74 ys)] patients were analyzed. Healthy subjects were included as controls. On liver biopsies histological parameters were evaluated. On serum samples TGF-ß1, hyaluronic acid (HA), tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), soluble Fas (sFas), caspase activity (CA) and caspase-generated cytokeratin-18 fragment (M30) were evaluated. In pediatric biopsies, 79% showed moderate or severe HAI, bridging fibrosis 46% and one cirrhosis. In adult cases, 76% showed moderate or severe HAI and the fibrosis profile displayed 5% stage (st) 0, 38% st 1, 33% st 2 and 24% st 3. 42% of pediatric and 81% of adult specimens showed lymphoid follicles. In pediatric biopsies minimal steatosis was observed in 37.5%, moderate 12.5% and severe 12.5%; meanwhile in adults 29%, 10% and 14%, respectively. Histological parameters showed no significant differences between groups except for lymphoid follicles (p= 0.01). TGF-ß1, TIMP-1, CA and M30 in HCV patients were higher than in controls. HA and sFas were high in HCV but only significant in adults. TGF-ß1 was associated with mild fibrosis in adults (p= 0.001). Higher HA and TIMP-1 were related with worse fibrosis stages, but HA was only significant in adults (p= 0.001) and TIMP-1 in children (p= 0.04). Interestingly, uppermost values for HA (239.6 ng/ml) and TIMP-1 (791.2 ng/ml) in children corresponds to the cirrhosis. HA and TIMP-1 displayed similar profile in both groups; but are elevated in pediatric severe HAI (p< 0.001). sFas was associated with fibrosis progression (p= 0.01 in pediatric, p= 0.02 in adults). In pediatric patients sFas was associated with severe HAI (p= 0.02). CA was associated with severe HAI (p