M. Del Ben

Clinical trial: low plasma cholesterol and oxidative stress predict rapid virological response to standard therapy with peginterferon and ribavirin in HCV patients

Background  Rapid virological response (RVR) is the best predictor of sustained response to standard HCV treatment.

Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver

Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchis echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2α, soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) μIU/mL in mild, moderate, and severe steatosis, respectively; P < 0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2α, soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchis score, urinary 8-iso-PGF2α, and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R 2 = 0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.

Effects of dark chocolate on NOX‐2‐generated oxidative stress in patients with non‐alcoholic steatohepatitis

Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non‐alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans.

P812 NOX2-GENERATED OXIDATIVE STRESS IS INCREASED IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE INDEPENDENTLY FROM METABOLIC SYNDROME

Background and Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) has a spectrum of disease severity beginning with steatosis. However, descriptions of prevalence and patient follow-up data are minimal. The aim was to determine the prevalence of hepatic steatosis using accepted computed tomography (CT) criteria, and to determine the follow-up rate of radiology-reported steatosis. Methods: A retrospective chart review was performed on all afterhours chest or abdominal CT scans in London, Canada, between January 1 and July 31, 2011. Follow-up was determined by electronic chart review and by contacting patients’ family physicians. Liver and spleen attenuation was calculated using accepted CT criteria to determine steatosis. Results: Over a 6-month period in 2011, 1259 Emergency Room CT Scans were performed, 450 met inclusion criteria. Forty-eight patients had reported findings of steatosis. No patients had followup bloodwork or testing and 2 of 48 patients had follow-up arranged with their family physician. Four hundred and five patients were included in the attenuation analysis. One hundred of the 405 included patients (24.7%) met CT criteria for steatosis (40/46 with radiology-reported steatosis and 60/359 without reported steatosis). Radiologist reporting of the incidental-steatosis had a sensitivity of 40% and specificity of 98% when compared to CT criteria for steatosis. Conclusions: This study was the first to provide steatosis prevalence data in Canada. The prevalence reported here is above the global average, but below reported American prevalences. Under-reporting and lack of follow-up on reported steatosis may lead to suboptimal care of these patients.

Towards predicting the therapeutic response in patients with hepatitis C: authors’ reply

SIRS , We thank Professor Féray for his comments concerning our study on the predictive role of high serum cholesterol in the rapid virological response to standard Peg-IFN-ribavirin therapy in HCV patients. Consistent with a recent study, our findings suggest that having higher cholesterol levels prior to treatment may favour a good outcome of therapy, given that achievement of rapid virological response is considered the strongest predictor of sustained response. Competition between serum lipoproteins and HCV lipo-viral particles for shared hepatocyte lipoprotein receptors may explain this association. Hepatitis C virus entry into hepatic cells is a multi-step process mediated by a strong interaction between virus and different lipoprotein classes. Indeed, HCV circulates in patient sera in the form of triglyceride-rich particles and consequently, lipoproteins and lipoprotein receptors may play an important role in hepatic virus uptake. 5 For reasons of the association of HCV with apoBand apoEcontaining low-density and very low density lipoproteins, the LDL receptor has been proposed as a potential entry factor for HCV. Although the function of LDL-R in REFERENCES