No abstract

BACKGROUND & AIMS: There have been few reproducible studies of mortality in patients with autoimmune hepatitis (AIH) and its variants. We calculated mortality in a large national cohort of patients with AIH, with vs without cirrhosis, in the Netherlands. METHODS: We collected data from 449 patients with established AIH (77% female), from 6 academic and 10 non-academic hospitals in the Netherlands. We identified 29 patients with AIH and primary biliary cholangitis and 35 patients with AIH and primary sclerosing cholangitis (AIH-PSC). Mortality and liver transplantation data were assessed from August 1, 2006 through July 31, 2016. Standardized mortality ratios (SMR) were calculated using age-, sex-, and calendar yearmatched mortality for the general Dutch population.

Interval cancers were detected in MLH1 and MSH2 mutation carriers, especially in those with a history of previous CRC and between 40 and 60 years. Interval cancer could be related to incompleteness of previous endoscopy and possibly residual adenomatous tissue. Further reduction of the interval cancer risk may be achieved by optimizing endoscopy quality and individualization of surveillance guidelines.

Almost 50 % of all Helicobacter pylori isolates are resistant to metronidazole, which reduces the efficacy of metronidazole-containing regimens, but does not make them completely ineffective. This discrepancy between in vitro metronidazole resistance and treatment outcome may partially be explained by changes in oxygen pressure in the gastric environment, as metronidazole-resistant (Mtz R ) H. pylori isolates become metronidazole-susceptible (Mtz S ) under low oxygen conditions in vitro. In H. pylori the rdxA and frxA genes encode reductases which are required for the activation of metronidazole, and inactivation of these genes results in metronidazole resistance. Here the role of inactivating mutations in these genes on the reversibility of metronidazole resistance under low oxygen conditions is established. Clinical H. pylori isolates containing mutations resulting in a truncated RdxA and/or FrxA protein were selected and incubated under anaerobic conditions, and the effect of these conditions on the MICs of metronidazole, amoxycillin, clarithromycin and tetracycline, and cell viability were determined. While anaerobiosis had no effect on amoxycillin, clarithromycin and tetracycline resistance, all isolates lost their metronidazole resistance when cultured under anaerobic conditions. This loss of metronidazole resistance also occurred in the presence of the protein synthesis inhibitor chloramphenicol. Thus, factor(s) that activate metronidazole under low oxygen tension are not specifically induced by low oxygen conditions, but are already present under microaerophilic conditions. As there were no significant differences in cell viability between the clinical isolates, it is likely that neither the rdxA nor the frxA gene participates in the reversibility of metronidazole resistance. INTRODUCTIONHelicobacter pylori is a spiral-shaped, Gram-negative bacterium that colonizes the stomach of approximately half the world's population (Blaser & Berg, 2001). Colonization with H. pylori is the most common cause of chronic active gastritis and peptic ulcer disease, and is strongly associated with the development of gastric cancer and gastric lymphoma. Unless treated with antibiotics, H. pylori colonization tends to persist for life. Cure of H. pylori infection results in ulcer healing and may reduce the risk of gastric cancer and gastric lymphoma development (Sugiyama et al., 2002;Wilhelmsen & Berstad, 1994). In vitro, H. pylori is susceptible to the majority of antibiotics, but for effective treatment a combination of drugs is required (Debets-Ossenkopp et al., 1999b). Currently used anti-H. pylori therapies often consist of two antibiotics with a proton pump inhibitor and/or a bismuth component (Malfertheiner et al., 2002). Metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole] is a key component of such combination therapies (Malfertheiner et al., 2002;van der Hulst et al., 1996).In Western Europe it has been estimated that 20-45 % of the H. pylori isolates are metronidazole-resistant (Mtz R ) (Glupczynski et al...