Dominique Wendum1,2, Richard Layese3,4, Nathalie Ganne-Carrié5,6,7, Valérie Bourcier5, Fatiha Merabtene2,8, Carole Cagnot9, Emmanuel Sauce10, Nathalie Barget10, Pierre Bedossa11, Benoit Terris12, Janick Selves13, Paulette Bioulac-Sage14,15,16, Nathalie Sturm17, Christophe Sattonnet18, Pierre Nahon5,6,7, Françoise Roudot-Thoraval3,4, Marianne Ziol6,7,10. 1. APHP, Hôpital St. Antoine, Anatomie Pathologiques. 2. Sorbonne Universités, UPMC Université Paris 06, INSERM UMRS_938 Centre de Recherche St. Antoine (CRSA), Paris, France. 3. APHP, Hôpital Henri Mondor, Unité de recherche clinique (URC-Mondor), Service de Santé Publique, AP-HP, Hôpital Henri-Mondor, Créteil, France. 4. Université Paris Est (UPEC), IMRB, A-TVB DHU, CEpiA EA 7376 (Clinical Epidemiology and Ageing Unit), Créteil, France. 5. APHP, Hôpital Jean Verdier, Service d'hépatologie, Bondy, France. 6. Université Paris 13, Sorbonne Paris-Cité, Bobigny, France. 7. INSERM UMR 1162, Génomique fonctionnelle des tumeurs solides, Université Paris Descartes, Université Paris Diderot, France. 8. Sorbonne Universités, UMS 30 LUMIC plateforme d'histomorphologie St. Antoine. 9. ANRS, Paris, France. 10. APHP, Hôpital Jean Verdier, Anatomie Pathologique et CRB BB-0033-00027, Bondy, France. 11. APHP, Hôpital Beaujon, Département de Pathologie, Clichy, France. 12. APHP, Hôpital Cochin, Anatomie Pathologique, Paris, France. 13. IUCT-Oncopole Toulouse, Departement d'Anatomie Pathologique, Toulouse, France. 14. Pathology Department, Pellegrin Hospital, CHU Bordeaux. 15. Inserm, UMR1053 Bordeaux Research in Translational Oncology BaRITOn. 16. Université Bordeaux, UMR1053 Bordeaux Research in Translational Oncology BaRITOn, Bordeaux, France. 17. CHU Grenoble, Département de Pathologie, Grenoble, France. 18. Selarl Diag, Nice, France.
Abstract
Progenitor-derived regeneration gives rise to the aberrant expression of biliary markers such as cytokeratin 7 (K7) and epithelial cell adhesion molecule (EpCAM) in hepatocytes. We aimed to describe the expression of these molecules in patients with compensated hepatitis C virus (HCV)-related cirrhosis and to investigate its potential influence on cirrhosis complications. Among patients with Child-Pugh A uncomplicated HCV-related cirrhosis enrolled in the prospective ANRS CO12 CirVir cohort, we selected individuals with a liver biopsy collected within 2 years before inclusion in the study. K7 and EpCAM immunostaining identified intermediate hepatobiliary cells. The influence of biliary marker expres-sion in hepatocytes on decompensation events and the occurrence of hepatocellular carcinoma (HCC) was studied using a multivariate Cox proportional hazards regression model. Among the 337 patients eligible for the study (men, 67%; median age, 52 years), 198 (58.8%) had biopsies with K7-positive hepatocytes including extensive staining in 40 (11.9%) and 203 had EpCAM-positive hepatocytes (60.6%). During follow-up (median, 54.2 months), 47 patients (14%) experienced a decompensation event, and HCC was diagnosed in 37 patients (11%). Extensive K7 staining was independently associated with the occurrence of a decompensation event (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.30-6.89; P = 0.010). EpCAM expression was independently associated with HCC occurrence (HR, 2.37; 95% CI, 1.07-5.23; P =0.033) along with age and a low prothrombin ratio. CONCLUSION: Progenitor-derived regeneration depicted by K7 and EpCAM immunostaining of hepatocytes in liver biopsies of patients with compensated HCV-related cirrhosis marks a cirrhosis stage more prone to develop complications. (HEPATOLOGY 2018; 68:1534-1548).
Progenitor-derived regeneration gives rise to the aberrant expression of biliary markers such as cytokeratin 7 (K7) and epithelial cell adhesion molecule (EpCAM) in hepatocytes. We aimed to describe the expression of these molecules in patients with compensated hepatitis C virus (HCV)-related cirrhosis and to investigate its potential influence on cirrhosis complications. Among patients with Child-Pugh A uncomplicated HCV-related cirrhosis enrolled in the prospective ANRS CO12 CirVir cohort, we selected individuals with a liver biopsy collected within 2 years before inclusion in the study. K7 and EpCAM immunostaining identified intermediate hepatobiliary cells. The influence of biliary marker expres-sion in hepatocytes on decompensation events and the occurrence of hepatocellular carcinoma (HCC) was studied using a multivariate Cox proportional hazards regression model. Among the 337 patients eligible for the study (men, 67%; median age, 52 years), 198 (58.8%) had biopsies with K7-positive hepatocytes including extensive staining in 40 (11.9%) and 203 had EpCAM-positive hepatocytes (60.6%). During follow-up (median, 54.2 months), 47 patients (14%) experienced a decompensation event, and HCC was diagnosed in 37 patients (11%). Extensive K7 staining was independently associated with the occurrence of a decompensation event (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.30-6.89; P = 0.010). EpCAM expression was independently associated with HCC occurrence (HR, 2.37; 95% CI, 1.07-5.23; P =0.033) along with age and a low prothrombin ratio. CONCLUSION: Progenitor-derived regeneration depicted by K7 and EpCAM immunostaining of hepatocytes in liver biopsies of patients with compensated HCV-related cirrhosis marks a cirrhosis stage more prone to develop complications. (HEPATOLOGY 2018; 68:1534-1548).
Authors: Martti Färkkilä; Johanna Arola; Nelli Sjöblom; Sonja Boyd; Anniina Manninen; Anna Knuuttila; Sami Blom Journal: Diagn Pathol Date: 2021-05-06 Impact factor: 2.644
Authors: Karim Hamesch; Nurdan Guldiken; Mahmoud Aly; Norbert Hüser; Daniel Hartmann; Pierre Rufat; Marianne Ziol; Katharina Remih; Georg Lurje; Bernhard Scheiner; Christian Trautwein; Mattias Mandorfer; Thomas Reiberger; Sebastian Mueller; Tony Bruns; Pierre Nahon; Pavel Strnad Journal: BMC Med Date: 2020-11-12 Impact factor: 8.775