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Background and Aims: It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy. Methods: In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively. Results: Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m2) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51–4.25) and 2.56 (95% CI: 1.14–5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61–2.33). Conclusions: Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.

Background: Sulforaphane (SFN) is a phytochemical compound which belongs to isothiocyanates family found in abundance in broccoli sprouts. SFN induces a variety of antioxidant enzymes via NF-E2-related factor 2-Kelch-like ECH-associated protein 1-mediated pathway, thereby protecting cells from injury induced by various kinds of oxidative stresses. We have previously shown that SFN protects gastric mucosa from oxidative injury induced by H. pylori infection. SFN also down-regulates histone deacetylase (HDAC) activity, thereby inducing apoptosis and inhibiting proliferation of tumor cells in variety of tissues. On the other hand, the incidence of colon cancer has increased in Japan. Since numerous epidemiological studies have shown that colon cancer is inversely associated with intake of anti-oxidant vegetables, we examined whether daily intake of SFN prevents colon tumorigenesis in mice and human subjects. Methods 1. Effects of SFN on Colonic tumorigenesis in Mice Treated with Chemical Carcinogen: Effects of SFN on colonic tumorigenesis were examined in the ICR male mice, pretreated with a chemical carcinogen, azoxymethane (AOM) (15 mg/kg). The mice treated with AOM for 3 or 6 times were fed for 8 or 24 weeks with or without sulforaphane glucosinolates (SGS: 2,200 ppm/kg/day), which is a precursor of SFN. Effects of SGS treatment on formation of the microscopic aberrant crypt foci (ACF) and the macroscopic tumors in colonic mucosa were evaluated. 2. Effects of SFN on formation of Colonic ACF in patients with colonic adenoma: Effects of intake of raw broccoli sprouts (BS), 50 g/day containing 220 mg SGS every other day, for 6 months on changes in the number of ACF in rectal mucosa was examined by colonoscopy in patients with colonic adenoma. 3. Effects of SFN on intestinal microbiota in human subjects: Effects of dietary intake of raw BS, 20 g/day, which contains 88 mg SGS every other day, for 2 weeks on intestinal microbiota in healthy volunteers was assessed by measuring composition of stool bacteria, using a method of terminal restriction fragment length polymorphism flora analysis. In human studies, alfalfa sprouts, which contains no SFN, was used as a placebo control. Results: 1. Daily administration of SGS suppressed formation of microscopic ACF and macroscopic colonic tumors in the AOM-pretreated mice in vivo. 2. Intake of BS for 6 months tended to decrease the number of colonic ACF in patients with colonic adenoma. 3. Intake of BS for 2 weeks increased percentages of Bifidobacterium and Clostridium XVIa, which has been shown to enhance protection of colonic mucosa by increasing butyrate production in colonic lumen. Conclusions: 1. Daily intake of SFN affords chemoprotection against colonic tumors in the mice treated with a chemical carcinogen. 2. The present study further suggests that, in addition to previously reported mechanisms, changes in the intestinal microbiota by SFN intake may also play a role in chemoprevention against colon cancer. Further studies are required to prove this possibility. [ABSTRACT FROM AUTHOR]

Background and study aims: The optimal method of perioperative management of antiplatelet agents during endoscopic procedures that carry a high risk of bleeding is still controversial. The aim of this study was to evaluate the safety of continuing aspirin treatment during these procedures in an Asian population. Patients and methods: Amulticenter, prospective, observational cohort study was conducted at six high volume endoscopy centers in Japan. The study included patients at high risk of thromboembolism whowere regularly taking antiplatelet agents (e. g. thienopyridine derivatives and aspirin). Enrolled patients continued their aspirin therapy, and underwent endoscopic procedures that had a high risk of bleeding for treatment of lesions in the upper and lower gastrointestinal tracts. The primary end point was the rate of major bleeding complications after endoscopic procedures. Results: The study was terminated in accordance with predetermined safety criteria because 7 of 28 consecutive patients experienced major bleeding complications (25.0 %; 95% confidence interval 10.7%-44.9 %). All major bleeding complications occurred following endoscopic submucosal dissection (ESD; 6 stomach, 1 colon). Univariate analysis showed that postoperative administration of thienopyridine derivatives was the only significant factor associated with postoperative bleeding (P=0.01). Subanalysis of gastric ESD (23 lesions in 19 patients) confirmed that the administration of thienopyridine derivatives (P=0.01) and that of multiple agents (P=0.02) were the significant factors. All bleeding complications (postoperative day 11.2±3.5) occurred after resuming thienopyridine derivative therapy postoperatively (postoperative day 2.3±2.4). Conclusion: In Asian patients taking thienopyridine derivatives with aspirin, cautious postoperative care is necessary for those undergoing endoscopic procedures that are associated with a high risk of bleeding, especially gastric ESD. Continuation of aspirin alone during these endoscopic procedures may be acceptable. [ABSTRACT FROM AUTHOR]