The Hepatitis Aggressiveness Score (HAS): a novel classification system for post-liver transplantation recurrent hepatitis C.

Abstract

Several histopathologic features have been described in cases of fibrosing cholestatic hepatitis C (FCH-C). We investigated whether FCH-associated features can be utilized as the basis of a novel grading system for the entire population of post-liver transplantation (LT) recurrent hepatitis C virus (HCV) infection. Liver biopsies obtained at a median (interquartile range) of 12.3 (10.4-13.8) months post-LT from 170 patients with recurrent HCV were included. Biopsies were assessed for the following FCH features: (1) ductular reaction, (2) cholestasis, (3) hepatocyte ballooning, and (4) periportal sinusoidal fibrosis. A Hepatitis Aggressiveness Score (HAS) was assigned on the basis of the number of FCH features as follows: 0 features=HAS 1; 1 to 2 features=HAS 2; and 3 to 4 features=HAS 3. We analyzed the performance of this novel system in predicting clinicopathologic outcomes compared with conventional grading systems after a median (interquartile range) follow-up of 24 (13-45.5) months. The HAS classification was highly predictive of fibrosis progression (P<0.001) and was the best predictor of graft loss in a multivariable analysis model, which included all conventional hepatitis grading systems (adjusted hazard ratio=5.5, confidence interval 2.9-10.7, P<0.001 for HAS 3 vs. HAS 1 and 2, compared with adjusted hazard ratio=1.0, confidence interval 0.5-1.9, P=0.94 for the presence of moderate to severe necroinflammation by at least 1 conventional grading system). Presence of at least 3 of 4 FCH features (HAS 3 group) characterized a subset of patients with distinctly worse prognosis and severe cholestatic disease (ie, FCH-C). We propose a novel approach to the histologic grading of post-LT recurrent HCV based exclusively on FCH features. This system allows accurate identification of FCH-C cases and stratification of all recurrent HCV patients into distinct prognostic categories.