T-5 Oncostatin M, overexpressed in hepatocellular carcinoma, up-regulates SERPIN-B3 expression in hepatic cancer cells

Abstract

Background: In the western world HCV is the leading etiologic factor of HCC. Overall HCV impact on HCC-related mortality is increasing, but recent data from Italy suggest an initial drop. Aims: To evaluate epidemiology, clinical features and survival of HCV-related HCC in a wide time range in Italy. Methods: Multicenter retrospective study including 2769 patients prospectively recruited by the ITA.LI.CA group. The patients were classified in 3 groups (Group A [G.A.], HCV associated or not with other etiologies, Group B [G.B.], pure HCV, and Group C [G.C.], alternative etiologies) and sub-grouped in 5 years time cohorts (1986-90, 91-95, 96-2000, 2001-2005) but for the last one (2006-2008). Age, gender, Child-Pugh status, diagnosis for surveillance, stage, thrombosis and metastases, treatment and survival (Kaplan-Meier, Log-Rank) were analyzed. Results: 1780 patients were included in G.A., 1430 in G.B., 989 in G.C. The number of G.A. and G.B. patients reached a peak in the 1996-2000 to then gradually drop, lowest values being observed in the last three years (p=0.0001 G.A., 0.01 G.B.). Mean age at diagnosis progressively increased in G.A. (p<0.0001) and G.B. (p<0.001), but not in G.C, as did the percentage of cases diagnosed under surveillance (G.A. p=0.019, G.B. p=0.0038) and the share of patients in Child-Pugh A stage (G.A. p=0.01, G.B. p=0.007). Tumor size decreased in all subgroups, stage improved significantly only in G.B. Median survival significantly increased in all groups but more significantly in G.A. and G.B., with a significant difference among G.A. and G.B. vs G.C. in the last 3 time periods (p=0.02). Conclusions: The incidence of HCC in HCV-related liver disease is decreasing in Italy since 2001. HCV-related HCC patients are older, more frequently diagnosed under surveillance, more frequently characterized by conserved liver function and smaller tumors, with an earlier tumor stage when HCV is the only etiologic factor. Finally their survival dramatically improved in the last 15 years, more than in patients with different etiology. We therefore expect a further drop in incidence and mortality for the disease in Italy in the years to come.