Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play an important role in alcohol dependence. In the present study, we analysed genome-wide DNAm profiles of purified CD3+ T-cells from pre- and post-treatment alcohol dependent patients, as well as closely matched healthy controls. We identified 59 differentially methylated CpG sites comparing patients prior to treatment with healthy controls and were able to confirm 8 of those sites in additional analyses for differentially methylated regions. Comparing patients before and after a 3-week alcohol treatment program we revealed another unique set of 48 differentially methylated CpG sites. Additionally, we found that the mean global DNAm was significantly lower in patients prior to treatment compared to controls, but reverted back to levels similar to controls after treatment. We validated top-ranked hits derived from the epigenome-wide analysis by pyrosequencing and further replicated two of them in an independent cohort and confirmed differential DNAm of HECW2 and SRPK3 in whole blood. This study is the first to show widespread DNAm variation in a disease-relevant blood cell type and implicates HECW2 and SRPK3 DNAm as promising blood-based candidates to follow up in future studies.

Zusammenfassung Ziel der Studie Ziel dieser Untersuchung war es, die derzeitigen Versorgungs- und Kontrollstrukturen für Patient*innen mit äthyltoxischer Leberzirrhose in der Vorbereitung auf eine Lebertransplantation (LTX) an deutschen Transplantationszentren zu erfassen. Es sollten zudem die damit einhergehenden Barrieren sowie die Sicht der Behandler*innen auf Verbesserungsmöglichkeiten für die Versorgung der Patient*innengruppe analysiert werden. Methodik In einem explorativen, deskriptiven, qualitativen Design wurden 11 Interviews mit Behandler*innen aus 10 der 22 deutschen LTX-Zentren geführt und inhaltsanalytisch ausgewertet. Ergebnisse Es zeigten sich deutliche Unterschiede in den Versorgungs- und Kontrollstrukturen der einzelnen Zentren. In das Behandlungskonzept integrierte suchttherapeutische Angebote gab es nicht an allen Zentren. Strukturelle Barrieren entstanden durch eine unzureichende Finanzierung und personelle Ausstattung. Behandler*innen wünschten sich erweiterte Behandlungsangebote sowie vereinheitlichte Behandlungskonzepte. Schlussfolgerungen Es zeigte sich Handlungsbedarf sowohl im Bereich der Strukturen der einzelnen LTX-Zentren als auch übergreifend auf Systemebene. Diese Ergebnisse könnten unter Berücksichtigung aktueller suchtmedizinischer Erkenntnisse als Grundlage zur Entwicklung von Behandlungskonzepten und -empfehlungen zur Optimierung der Versorgung vor LTX dienen.

No abstract

Background Similar to many other countries, in Germany patients with alcohol-related liver disease are obliged to prove their abstinence before being accepted on a waitlist for liver transplantation. Health care professionals (HCPs) must both treat patients and ensure that patients have proven their abstinence. The aim of this exploratory study was to develop a deeper understanding of how HCPs deal with this dual role. Methods The study used semi-structured interviews as the source of data. 11 healthcare professionals from ten of the 22 German transplant centers were interviewed. After transcription, a qualitative content analysis was performed. Results We found that these HCPs faced an ethical dilemma, as they must balance the roles of being both a treatment provider (the therapist role) and an assessor (the monitoring role). To solve this dilemma, the strategy seems to be a tendency for the HCPs to take on one dominant role amongst these two roles. HCPs who prefer to take on the therapist role seem to feel burdened by the 6-month abstinence rule and the obligation to monitor their patients. HCPs who prefer to take on the monitoring role tend to have negative assumptions about the patients. HCPs also reported the impression that patients perceive HCPs as more involved in monitoring and less open to the therapeutic role. From this it can be deduced that current regulations and structures lead both to stress for HCPs and to suboptimal therapy for those affected. Conclusions The results showed that current transplantation guidelines can have a negative impact on both patient care and the burdens on the HCPs. From our point of view, there are various changes that could be made to the current clinical practice that would help solve this dilemma. For instance, integrating other assessment criteria that are more closely adapted to the health status trajectory and psychosocial background of the individual patient would be both possible and would lead to improvements in practice.