Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL.

BACKGROUND & AIMS: Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible. METHODS: SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 ("Check-up 35") at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score >0.5 were referred to a liver expert in secondary and/or tertiary care. RESULTS: A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83‰ vs. 3.36‰). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51‰, controls: 2.21‰). CONCLUSIONS: The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program. REGISTRATION: DRKS00013460 LAY SUMMARY: Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the 'SEAL' pathway represents a feasible and potentially cost-effective screening program.

Clinical management of eosinophilic esophagitis - a nationwide survey among gastroenterologists in Germany.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly recognized immune-mediated esophageal disease and a common cause for dysphagia and food bolus obstruction. The aim of this study was to evaluate the current clinical management of EoE among adult gastroenterologists in Germany. METHODS: We performed a cross-sectional study of 1393 adult gastroenterologists using a questionnaire containing 22 questions to general, diagnostic, and therapeutic aspects of EoE. The self-administered online survey was conducted between November 2017 and February 2018. Data capture and analysis was performed using SurveyMonkey. RESULTS: The overall responder rate was 29.6 %. More than half of the responders (54.9 %) felt to observe a significant increase of EoE patients. The EREFS score was mostly either unknown (44.3 %) or not routinely used (52.2 %). If EoE was suspected, most responders obtained multiple esophageal biopsies (n = 3 - 4: 35.7 %; n > 4: 61.6 %). The preferred primary treatment was proton pump inhibitors (PPI) in 37.2 % and topical steroids in 35.0 % of responders. PPI regimens were highly diverse, with only half of responders using high-dose PPI regimens. Allergy testing was often initiated (always 25.4 %, sometimes 48.9 %). The most common dietary therapy was 6-food elimination diet (52 %), followed by allergy test-directed diets (16 %) and 2-food elimination diet (16.5 %). The majority of responders indicated a need for long-term treatment (i. e., 23 % of responders in > 50 % their patients and 47.7 % of responders in 25 - 50 % of their patients). CONCLUSIONS: Among gastroenterologists in Germany, substantial variation in the adherence to published EoE guidelines appears to exist. This indicates the need for intensified education and national guidelines in order to optimize and harmonize the clinical management of EoE patients.

Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration.

In a randomized, double-blind, placebo-controlled, four-way crossover study, possible influences of the triple therapy with amoxicillin, clarithromycin and the proton pump inhibitor lansoprazole on the pharmacokinetics of each of the drugs and the active 14-OH-clarithromycin metabolite were assessed. Twelve Helicobacter pylori-negative healthy male volunteers (age 27 +/- 4.3 years; creatinine clearance 7.0 +/- 2.0 L/h) were given lansoprazole 30 mg, amoxicillin 1 g and clarithromycin 500 mg, alone and in triple combination. Drug elimination intervals were at least 9 days between the dosing periods. The study medication was administered twice daily for 4 days. On the fifth day of each period, drugs were only given once in the morning, and blood and urine samples were collected for 12 h. The concentrations of the three substances administered, and 14-OH-clarithromycin, were determined by validated HPLC methods. Alterations in the serum kinetics were found for lansoprazole and the active 14-OH-clarithromycin metabolite (all data expressed as mean +/- S.D.). For lansoprazole, the elimination half-life (t(1/2)) was significantly prolonged (1.46 versus 1.7 h, P < 0.05) and the area under the concentration-time curve from 0 to 8 h (AUC(0-8)) was significantly increased (3.65 versus 4.59 mg.h/L, P < 0.05) by combination of the drugs. For 14-OH-clarithromycin, the peak concentration (C(max)) was 0.95 versus 1.18 mg/L and the AUC from 0 to 12 h (AUC(0-12)) was 8.3 versus 10.5 mg.h/L (augmented significantly, P < 0.05). The amoxicillin concentrations were slightly elevated by concomitant administration of lansoprazole and clarithromycin but without statistical significance (11.1 versus 12.6 mg/L). For clarithromycin, the time to maximum concentration of drug in serum (T(max)) was increased (2.73 versus 3.31 h, P < 0.05), whereas AUC and C(max) remained unchanged. Simultaneous administration of lansoprazole, amoxicillin and clarithromycin increases the serum concentrations of lansoprazole and the active 14-OH-clarithromycin metabolite significantly. These effects were not so pronounced as to have any therapeutic influence, making dosage adjustment unnecessary.