Pediatric Hepatitis C virus (HCV) chronic infection: A potential serum marker reflects liver apoptosis and degree of steatosis

VALVA P; DE MATTEO E; GISMONDI MI; LEZAMA C; GALOPPO MC; PRECIADO MV

Cataratas del Iguazú

Congreso; III World Congress of Pediatric Gastroenterology, Hepatology and Nutrition; 2008

In Hepatitis C virus chronic infection apoptosis may play a role in pathogenesis as well as steatosis may influence disease progression. Cytokeratins (CK) have been studied as serum markers of liver disease. Recent evidence suggests that CK-18 is cleaved by caspases and released from apoptotic cells. Our aim was to detect early apoptosis markers in liver biopsies and serum samples from pediatric HCV+ patients and to assess the usefulness of a serum marker of liver injury progression. Twenty patients [median age: 8.5 years (range 1-17 yrs)] were included. Fibrosis (F), hepatitis (H), steatosis, lymphoid follicles and bile duct damage were assessed in liver biopsies. HCV infected hepatocytes (NS3) and apoptosis markers (activated caspase-3 [casp-3a] and caspase-generated CK-18 fragment [M30]) were evaluated by immunohistochemistry. Results were expressed as nº positive hepatocytes/nº total hepatocytes in 20 high-power fields (1000). In a subgroup of 14 serum samples, at time of biopsy, M30 was quantified. A group of 8 controls was included. Forty percent of biopsies displayed F1, 50% F2 and 10% F3. Thirty five percent showed mild H and 65% moderate H. No patient displayed cirrhosis or severe H. Sixty percent of biopsies showed variable steatosis (<10-85%), 45% lymphoid follicles and 75% bile duct damage. All patients’ liver samples showed NS3 labeling [median: 0.22 (0.004-0.88)], 90% casp-3a [median: 0.06 (0.003-0.256)] and 70% M30 [median: 0.015 (0.002-0.14)]. NS3 labeling did not display association with worse histological parameters, but showed statistically significant correlation with casp-3a (r=0.70; p=0.0007). Concerning apoptosis markers, only casp-3a was associated with high fibrosis stages (p=0.01), but not with other histological parameters. Controls did not show NS3, M30 or casp-3a labeling. Serum M30 values [median: 117.59U/L (95.35-794.59)] were significantly higher in HCV+ patients than in controls [median: 87.28U/L (72.90-94.23)] (p<0.0001). A correlation was observed between serum M30 and steatosis (r=0.60; p=0.02) as well as it was high in patients with advanced fibrosis. HCV would not have a direct effect on histological variables but it would be involved in liver damage through apoptosis induction. Both liver and serum apoptosis markers detected reflect liver injury. Although a greater children cohort must be analyzed, M30 quantification in serum might be useful as a maker to detect the extent of liver steatosis and fibrosis.