INVESTIGADORES
DE MATTEO Elena NoemÍ
congresos y reuniones científicas
Título:
Pediatric Hepatitis C virus (HCV) chronic infection: A potential serum marker reflects liver apoptosis and degree of steatosis
Autor/es:
VALVA P; DE MATTEO E; GISMONDI MI; LEZAMA ELECHARRI C; GALOPPO MC; PRECIADO MV
Lugar:
Brasil
Reunión:
Congreso; III World Congress of Pediatric Gastroenterology, Hepatology and Nutrition.; 2008
Institución organizadora:
European Society for Paediatric Gastroenterology Hepatology and Nutrition y North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
Resumen:
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.