Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer-assisted digital image analysis (DIA) of Sirius Red-stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively-transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty-two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 510). Portal hypertension (HVPG = 6 < 10 mmHg) was present in 30 (69.8%), and HVPG = 10 mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.7523.25). Median ChildPugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.312.4) versus 23% in stage 6 (IQR 1733.7, P < 0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically-significant portal hypertension (HVPG = 10 mmHg, odds ratio: 1.085, confidence interval: 1.0041.172, P = 0.040). A CPA of 14% was the best cut-off value for clinically-significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event-free survival was significantly shorter in patients with CSPH or with a CPA value = 14%, or with a combination of both. Conclusion: In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing early from late severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG = 10 mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification.