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Background and Aims: diabetes has been reported as a risk factor for hepatocellular carcinoma (HCC) in population-based studies but there are controversial data in patients with cirrhosis. Metformin could have a protective role in HCC development. The aim of this study was to determine the influence of diabetes on the risk of developing HCC in patients with alcohol- and hepatitis C virus (HCV)-related cirrhosis., Methods: a cohort of 982 Caucasian patients were analyzed with alcoholic or HCV cirrhosis, included from 1992 to 2014 in a HCC surveillance program and prospectively followed. The influence of diabetes on the development of HCC was analyzed by Kaplan Meier analysis and adjusted with a Cox regression for relevant co-factors., Results: after a median follow-up of 49.5 (24.0-96.0) months, 156 patients (15.8 %) developed HCC. There were no differences in the cumulative incidences of HCC after 20 years between diabetic and non-diabetic patients in the global (53.5 % vs 45.4 %; p = 0.26), alcoholic (50.4 % vs 45.4 %; p = 0.21) or HCV (60 % vs 43.1 %; p = 0.57) cirrhosis series. Diabetes did not constitute a risk factor after adjusting for other potential co-factors, neither in the whole series (hazard ratio [HR]: 1.12, 95 % CI: 0.78-1.51; p = 0.26), alcoholic (HR: 1.160, 95 % CI: 0.74-1.82; p = 0.50) or HCV cirrhosis cohort (HR: 1.17, 95 % CI: 0.63-2.19; p = 0.60). These figures did not change after excluding patients treated with metformin., Conclusions: in Caucasian patients with alcoholic or HCV cirrhosis, diabetes is not a risk factor for developing HCC. This lack of an association does not seem to be a consequence of the protective effect of metformin.

Objective: Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the inflammatory response and pathogenesis of Crohn's disease (CD). TNF-alpha -308A polymorphism within the TNF-alpha gene promoter has been associated with enhanced TNF-alpha production in vitro. The aim of this study was to investigate the effect of TNF-alpha promoter polymorphism at -308 on the susceptibility and phenotypic expression of fistulizing CD., Methods: The distribution of -308 TNF-alpha genotypes was analyzed in 50 patients with fistulizing CD and 100 healthy matched controls. TNF-alpha, interleukin-1beta, and interleukin-6 serum levels were measured by ELISA. Serum amyloid-A, C-reactive protein, alpha1-antitrypsin, alpha1-acid glycoprotein, and haptoglobin were measured by nephelometry., Results: No significant differences were found in the allele frequencies of the polymorphism between patients and controls. However, compared with -308GG patients, those carrying -308AG had a significant increase of serum levels of TNF-alpha (58 +/- 79 vs 8 +/- 19 pg/ml, p < 0.001), interleukin-1beta (36 +/- 45 vs 16 +/- 20 pg/ml, p = 0.048), and acute phase proteins (APPs). -308A carriers had also a higher frequency of arthritis (66% vs 26%, p = 0.039). The logistic regression model showed that the patients carrying -308A polymorphism had a relative risk for developing arthritis of 5.45 (95% CI = 1.1-25.6). No other clinical or analytical findings were predictive for the risk of development of arthritis., Conclusions: TNF-alpha -308A polymorphism is associated with enhanced TNF-alpha production, more intense inflammatory activity, and an increased risk for arthritis susceptibility in CD patients with fistulizing disease.