29 FROM NAFLD TO HCC: THE ROLE OF FIBROSIS AS A COFACTOR IN A NEW MOUSE MODEL

Abstract

Materials and Methods: Seventy OLT recipients were enrolled. The aetiology was HCV infection in 25 patients, HBV infection in 9, alcoholic disease in 30 and other in 6. Two per protocol liver biopsies (BIO1, BIO2) were performed: BIO1 within the first 60 postoperative days, BIO2 at one year. Significant ACR episodes were recorded during the first year; Ishak staging was assessed in BIO2. A fragment of BIO1 was stored for RT-PCR quantification of the following genes: Retinoic-acid-Inducible Gene I (RIG-I), CARD adaptor inducing IFN-b (CARDIF), Interferon Regulatory Factor 3 (IRF-3), Ubiquitin Specific Peptidase 18 (USP-18), Interferon-Stimulated Gene 15 (ISG-15), Suppressor Of Cytokine Signaling 1 and 3 (SOCS-1, SOCS-3), 2′-5′ OligoAdenylate Synthase 2 (OAS-2). Results: Seven patients (6 HCV positives) reached an Ishak staging >2 on BIO2. In 19 HCV+ patients with Ishak staging 2 on BIO2, higher mRNA expression of CARDIF (19.7±32.8 Vs 0.1±0.1; p 2. Eighteen patients experienced ACR. In these patients a lower mRNA expression of USP-18 (30.4±78.3 Vs 871.4±2631.2; p = 0.02) and RIG-I (0.3±0.5 Vs 13.5±38.5; p = 0.05) was found in comparison to the 52 patients who did not show significant ACR. The latter association was confirmed in HCV positive patients (0.4±0.6 Vs 16.6±45.3; p< 0.05). Conclusions: Early activation of genes involved in the II response may reduce liver fibrosis progression in HCV positive recipients. The activation of USP-18 and RIG-I may prevent the occurrence of ACR.