: Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC. We recruited 537 Caucasian CHC patients from three European centers (Brussels, Belgium [n = 229]; Hannover, Germany [n = 171]; Lyon, France [n = 137]); these patients were centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross-sectional and longitudinal manner. Seven other variants previously associated with fibrosis progression were included. Finally, we explored the impact of rs738409 on response to standard antiviral therapy using the interferon lambda 3 (IL28B) [rs12979860 C>T] variant both as a comparator and as a positive control. After adjustment for age, sex, body mass index, alcohol consumption, and diabetes, rs738409 mutant G allele homozygote carriers remained at higher risk for steatosis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.08–6.03, P = 0.034), fibrosis (OR 3.13, 95% CI 1.50–6.51, P = 0.002), and fibrosis progression (OR 2.64, 95% CI 1.22–5.67, P = 0.013). Conversely, rs738409 was not independently associated with treatment failure (OR 1.07, 95% CI 0.46–2.49, P = 0.875) and did not influence clinical or biological variables. Conclusion: The PNPLA3 (rs738409 C>G) polymorphism favors steatosis and fibrosis progression in CHC. This polymorphism may represent a valuable genetic predictor and a potential therapeutic target in CHC liver damage. (HEPATOLOGY 2011;)

Background and study aims: Bariatric surgical treatments have been proven to induce long-term weight loss in morbidly obese patients, but complications are relatively frequent. We recently reported a first human multicenter trial assessing the safety, feasibility, and weight loss results of the Transoral Gastroplasty (TOGA) system (Satiety Inc., Palo Alto, CA) at 6 months. Here we report the 6-month results of the second phase of the pilot trial with the TOGA system, with technical improvements to the device. Patients and methods: Patients met established criteria for bariatric surgery. The TOGA system, a set of transoral endoscopically guided staplers, was used to create a stapled restrictive pouch along the lesser curvature of the stomach. Follow-up was at 1 week and at 1, 3, and 6 months. At 3 months, re-treatment consisting in additional distal restrictions was allowed if necessary. Results: Data were available for 11 patients in our center (7 female, mean age 44.2 years, mean body mass index 41.6). The procedure was completed safely in all patients. There were no serious adverse events. Mean excess weight loss was 19.2 %, 33.7 %, and 46.0 % at 1, 3, and 6 months, respectively. Average body mass index decreased from 41.6 before treatment to 33.1 at 6 months. Absolute mean weight loss was 9.9 kg, 17.5 kg, and 24.0 kg at 1, 3, and 6 months, respectively. A dramatic improvement in quality-of-life measures was observed in all patients. Conclusions: This second pilot trial confirmed the feasibility and safety of transoral gastroplasty. The early results and technical improvements reported in the present study are encouraging in terms of safety, early weight loss, and quality of life, and clearly allowed multicenter trials, which are planned to start soon.