Abstract

Background: Albeit cirrhosis evolves through clinical stages to decompensation and death, the relation between the amount of fibrosis and the disease course is unknown. Digital image analysis of stained biopsy sections quantifies fibrosis, using segmentation of digital images to measure areas of collagen and to produce a collagen proportionate area (CPA). Aim: To correlate CPA with esophageal varices (EV) at baseline and SVR to SoC therapy in patients with compensated HCV cirrhosis. Patients and Methods: Eighty-six HCV-RNA positive, compensated patients with an histology of cirrhosis (Scheuer’s stage 4) were included. Biopsies were stained with Sirius-red to calculate CPA, excluding samples <15mm. All patients underwent endoscopic screening for EV before SoC treatment with Peg-IFN alfa-2b and Ribavirin. Mean follow up was 37±12 months. Results: Twenty-nine patients (33.7%) had EV. Seven biopsies were suboptimal. In 79 assessable patients, the mean value of CPA was 15.6±6.7%. Mean CPA was significantly different among patients with or without EV (17.9±7.9 vs 13.7±5.9; p = 0.010). By univariate analysis CPA (p =0.007) and albumin (p =0.096) were associated to EV but by multivariate logistic analysis CPA was the only variable associated with EV (OR: 1.086 95%CI: 1.005–1.172; p =0.036). By AUROC the best CPA cut-off value for EV was 14.1% (Sensitivity:80%; Specificity:70%; PPV:60%; NPV 83%). Nineteen patients (24.1%) had SVR. Mean CPA value in patients with SVR was lower than in nonSVR patients (16.6±6.4% vs 12.5±6.9%, p = 0.021). The best CPA cut-off value for SVR was 13% (Sensitivity:74%; Specificity:67%; PPV:40%; NPV:89%). At univariate analysis, CPA and PLT were associated to SVR, but only CPA was associated with SVR at multivariate analysis (OR: 1.012, 95%CI: 0.82–0.99; p = 0.046). Conclusion: The amount of fibrosis in a cirrhotic liver, quantified by CPA, correlates closely to the degree of portal hypertension. The inverse relation between CPA and likelihood of SVR to SoC may suggest use of the former as an additional parameter to indicate which patients with compensated HCV cirrhosis should receive therapy.

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