Summary Background Proton pump inhibitors (PPI) have no effect on non‐acid reflux events which can continue to provoke gastro‐oesophageal reflux disease (GERD) symptoms. Baclofen, a γ‐aminobutyric acid agonist, can decrease non‐acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. Aims To assess the efficacy of baclofen 10 mg t.i.d. vs placebo as add‐on therapy in PPI‐refractory GERD symptoms, in a randomised, double‐blind, placebo‐controlled study. Methods Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance‐pH monitoring on‐PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. Results About 60 patients were included (age 47.5 years [range 19–73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen‐treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n = 25) group improved significantly with baclofen (pcorr = 0.02), and worsened with placebo (pcorr = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (pcorr = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr = 0.009), but not placebo. Conclusion Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH‐impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.

Background. Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. Methods. Retrospective multicentre study of 79 patients who received LT for PSVD. Results. Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. Conclusions. LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

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Background: Functional dyspepsia (FD) is one of the most frequent conditions in gastroenterological outpatient health care. Most recent research in FD has shifted its focus to duodenal pathophysiological mechanisms, although current treatments still focus mainly the stomach. Aim:The aim of the study was to provide a comprehensive overview of the pathophysiology of FD focusing on a paradigm shift from gastric towards duodenal mechanisms. Methods:We conducted a literature search in PubMed for studies describing mechanisms that could possibly cause FD. Results:The pathophysiology of FD remains incompletely understood. Recent studies show that duodenal factors such as acid, bile salt exposure and eosinophil and mast cell activation correlate with symptom pattern and burden and can be associated with gastric sensorimotor dysfunction. The evolving data identify the duodenum an interesting target for new therapeutic approaches. Furthermore, the current first-line treatment, that is proton pump inhibitors, reduces duodenal low-grade inflammation and FD symptoms. Conclusion:Future research for the treatment of FD should focus on the inhibition of duodenal mast cell activation, eosinophilia and loss of mucosal integrity.(supporting). A. Verheyden: Writing -review and editing (supporting). T. Vanuytsel: Writing -review and editing (equal). J. Tack: Conceptualization (equal); writing -original draft (supporting); writing -review and editing (lead).

LINKED CONTENT This article is linked to Pauwels et al papers. To view these articles, visit https://doi.org/10.1111/apt.17068 and https://doi.org/10.1111/apt.17103