| Autor: |
Ziol, Marianne, Nault, Jean–Charles, Aout, Mounir, Barget, Nathalie, Tepper, Maryline, Martin, Antoine, Trinchet, Jean–Claude, Ganne–Carrié, Nathalie, Vicaut, Eric, Beaugrand, Michel, N'Kontchou, Gisele |
| Předmět: |
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| Zdroj: |
Gastroenterology (00165085); Jul2010, Vol. 139 Issue 1, p335-343.e2, 0p |
| Abstrakt: |
Background & Aims: The expression of biliary lineage markers such as cytokeratin (K) 7 by hepatocytes is thought to reflect an altered regeneration pathway recruiting a stem cell compartment, more prone to carcinogenesis. We aimed to investigate the presence of these so-called intermediate hepatobiliary cells (IHC) in liver biopsies of patients with hepatitis C–related cirrhosis and their potential influence on the subsequent occurrence of hepatocellular carcinoma (HCC). Methods: From a cohort of patients with hepatitis C–related cirrhosis, prospectively screened for HCC, we retrospectively selected those with a liver biopsy performed for the initial diagnosis of cirrhosis. Presence of IHC was recorded when foci of K7-positive, intermediate-sized hepatocytes were detected. Results: A total of 150 patients were included (87 men; mean age, 57 y; range, 19–84 y; body mass index, 25 kg/m2). After a median follow-up period of 4.85 years, HCC was diagnosed in 36 patients (24%). Baseline liver biopsy showed intermediate hepatobiliary cell foci in 61 patients (41%). Intermediate cells co-expressed both hepatocytes markers and the progenitor cell markers Ep-CAM and K19. The presence of intermediate hepatobiliary cells was associated independently with HCC occurrence (Fine and Gray model; hazard ratio, 2.48; 95% confidence interval, 1.24–4.96; P = .01). Other predictors of HCC were diabetes and low platelet count. The HCC annual incidence rate was significantly higher in patients with IHC compared with patients without (8.14% vs 3.12%, Gray''s test, P = .003). Conclusions: The aberrant expression of biliary K by hepatocytes in patients with hepatitis C virus–related cirrhosis is related independently to HCC occurrence. [Copyright &y& Elsevier] |
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