Chronic liver disease (CLD) and several related extrahepatic manifestations such as hepatic osteodystrophy are associated with deficiency of vitamin D, which has therefore been suggested as therapeutic target. Vitamin D undergoes hepatic 25‐hydroxylation, rendering the liver critical to the metabolic activation of this vitamin. Vitamin D deficiency is highly prevalent in CLD patients, and vitamin D levels are inversely related to the severity of CLD. Declining levels of carrier proteins such as albumin and vitamin D‐binding protein might also be critical in CLD. Intervention studies report improvements of CLD following supplementation, and benefits to health outcomes in particular with respect to hepatitis C virus infection have recently been documented.Content:We discuss vitamin D sources, functions and metabolism with a focus on the inherent complications of analytical measurements, such as the interference of 25‐hydroxyvitamin D and 1,25‐dihydroxyvitamin D C‐3 epimers. Global discrepancies in the definition of optimal serum 25‐hydroxyvitamin D levels are covered, and the prevalence of vitamin D deficiency in CLD is reviewed. We also address the functional mechanisms underlying this deficiency, and refer to associations between genetic variation in vitamin D metabolism and CLD. Lastly, we consider the health implications of a vitamin D deficiency in CLD and consider therapeutic options.Summary: Herein, we focus on the epidemiological and functional relationships between vitamin D deficiency and CLD, followed by a discussion of the potential implications for therapeutic interventions.

Die Leitlinie zur Prävention, Diagnostik und Therapie von Gallensteinen aktualisiert die Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie aus dem Jahr 2007. Die Leitlinie wurde interdisziplinär von Gastroenterologen und Chirurgen erstellt. Sie basiert auf den Empfehlungen der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften für eine systematische evidenzbasierte Konsensus-Leitlinie der Entwicklungsstufe S3 und berücksichtigt die klinische Anwendbarkeit der Studienergebnisse. Zudem werden Präventionsmöglichkeiten beschrieben, Qualitätsindikatoren definiert, ökonomische Auswirkungen berücksichtigt und Vorschläge zur sektorenübergreifenden Behandlung von Patienten mit Gallensteinerkrankungen formuliert. This guideline provides evidence-based key recommendations for the prevention, diagnosis and therapy of gallstones and upgrades the 2007 version. The guideline was developed by an interdisciplinary team of gastroenterologists and surgeons, and patient support groups under the auspice of the German Society for Gastroenterology and Metabolic Diseases and the German Society for General Surgery and Surgery of the Alimentary Tract. The guideline used structural S3 consensus-based methodology and includes statements on clinical practice, medical education, prevention, quality assurance, outcome analysis, and integration of outpatient and inpatient care for patients with gallstone diseases. ^* Walter Asperger, Christiane Bruns, Christoph Dietrich, Klaus Dirks, Jens Encke, Siegbert Faiss, Hubertus Feussner, Thomas Frieling, Matthias Glanemann, Jochen Hampe, Hermann Helmberger, Thomas P. Hüttl, Ralf Jakobs, Birgit Kallinowski, Reinhard Kubale, Erdmute Kunstmann, Matthias Maier, Stephan Miehlke, Jürgen Pauletzki, Steffen Rickes, Andreas Schreyer, Michael Sackmann, Peter Sauer, Tilman Sauerbruch, Michael Schepke, Florian Schreiber, Jochen Schuld, Albrecht Stier, Ingo van Thiel und Marty Zdichavsky.

Gallstone disease represents one of the most common and costly gastroenterological disorders. In Germany, 0.25% of the population undergo cholecystectomy per year, and cholelithiasis incurs annual medical expenses of more than USD 6.5 billion in the United States. The paradigm of environmental risk factors for gallstones has lately been challenged by genetic studies in experimental models and humans. The analysis of more than 40,000 Swedish twin pairs with gallstones demonstrated that genetic factors account for 25% of the phenotypic variance. Since then, studies employing genome-wide association analysis, case-control cohorts and analysis of sib-pairs in families with gallstones have expanded our knowledge of ‘gallstone genes’. Indeed, gallstone disease phenotypes are likely to result from the complex interaction of genetic factors, chronic overnutrition with carbohydrates, depletion of dietary fibre and other not fully defined environmental factors including physical inactivity and infections. This hypothesis is supported by the profound increases of cholesterol gallstone prevalence rates in Native Americans, post-war European countries and current urban centres in East Asia, all of which were associated with ‘westernized’ nutrition. Herein, we summarise the spectrum of environmental and genetic risk factors which should pave the way to ‘personalised’ strategies for the prevention and therapy of gallstones.

The prevalence of gallstones is increasing in association with the obesity epidemic, but rapid weight loss also increases the risk of stone formation. We conducted a systematic review of the efficacy of strategies to prevent gallbladder stones in adults as they lose weight. Randomized controlled trials of nonsurgical strategies to prevent gallstones were identified by electronic and manual searches. Our final analysis included 13 trials, comprising 1836 participants undergoing weight loss through dieting (8 trials) or bariatric surgery (5 trials). The trials compared ursodeoxycholic acid (UDCA) or high-fat weight loss diets with control interventions. We performed random-effects meta-analyses and evaluated heterogeneity and bias with subgroup, sensitivity, regression, and sequential analysis. UDCA reduced the risk of ultrasound-verified gallstones compared with control interventions (risk ratio, 0.33; 95% confidence interval [CI], 0.18-0.60; number needed to treat, 9). This effect was significantly larger in trials of diets alone (risk ratio, 0.17; 95% CI, 0.11-0.25) than in trials of patients who underwent bariatric surgery (risk ratio, 0.42; 95% CI, 0.21-0.83) (test for subgroup differences, P =.03). UDCA reduced the risk of cholecystectomy for symptomatic stones (risk ratio, 0.20; 95% CI, 0.07-0.53). Diets high in fat content also reduced gallstones, compared with those with low fat content (risk ratio, 0.09; 95% CI, 0.01-0.61). The meta-analyses were confirmed in trials with a low risk of bias but not in sequential analysis. No additional beneficial or harmful outcomes were identified. On the basis of a meta-analysis of randomized controlled trials, during weight loss, UDCA and/or higher dietary fat content appear to prevent formation of gallstones.