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Clinical Epidemiology and Ageing

Influence of Progenitor-Derived Regeneration Markers on Hepatitis C Virus-Related Cirrhosis Outcome (ANRS CO12 CirVir Cohort).

Wendum D, Layese R, Ganne-Carrié N, Bourcier V, Merabtene F, Cagnot C, Sauce E, Barget N, Bedossa P, Terris B, Selves J, Bioulac-Sage P, Sturm N, Sattonnet C, Nahon P, Roudot-Thoraval F, Ziol M Hepatology. 2018;68(4):1534-1548.

<p>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.</p><p><b>CONCLUSION: </b>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).</p>

MeSH terms: Adult; Aged; Biomarkers; Biopsy, Needle; Cohort Studies; Epithelial Cell Adhesion Molecule; Female; Hepacivirus; Hepatitis C; Humans; Immunohistochemistry; Keratins; Liver Cirrhosis; Liver Regeneration; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Stem Cells; Survival Rate
DOI: 10.1002/hep.29927

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