RESUMEN
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).
Asunto(s)
Hepacivirus/metabolismo , Hepatitis C/complicaciones , Queratinas/metabolismo , Cirrosis Hepática/virología , Células Madre/fisiología , Adulto , Anciano , Biomarcadores/metabolismo , Biopsia con Aguja , Estudios de Cohortes , Molécula de Adhesión Celular Epitelial/metabolismo , Femenino , Hepatitis C/mortalidad , Hepatitis C/patología , Humanos , Inmunohistoquímica , Cirrosis Hepática/patología , Regeneración Hepática/fisiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
In this prospective comparative study, compared with fertile control subjects (n = 12), infertile patients with hydrosalpinx (n = 18) had lower E-cadherin and a trend toward decreased N-cadherin H-scores in the endometrium (3.6 ± 0.6 vs. 2.4 ± 0.8 and 0.57 ± 1.0 vs. 0.52 ± 0.5, respectively). In hydrosalpinx, epithelial N-cadherin expression was discontinuous and disappeared in atrophic patches.