Clinical Case Summary

We present a case of a 46-year-old female admitted to our clinic with a 6day history of nausea, vomiting around 10-15 times with blood clots, heartburn, regurgitation, retrosternal pain, loss of appetite, dizziness, generalized weakness, jaundiced skin and sclerae. The patient had previously been diagnosed with left-sided ulcerative colitis, currently in remission without medications. She mentioned alcohol abuse of around 300ml cognac per day for the past 2 years.
Physical examination t=36,6 ^oC, BP=70/40 mm Hg. Blood tests showed macrocytic anemia, thrombocytopenia, hypokalemia, elevated values of total bilirubin, especially direct, ALT, AST, GGT, and ALP, creatinine, urea, low albumin level and coagulopathy.
EGDS showed circumferential black discoloration of the esophagus, which bled on contact (Gurvits syndrome or black esophagus) and a coffee grounds resembling sediment in the stomach. PPI therapy was initiated.
An abdominal ultrasound found hepatomegaly, vena portae=11mm. A diagnosis of alcohol-related liver disease was made and corticosteroid therapy was initiated (32mg methylpredinosolone/day). Maddrey’s Discriminant Function was 41.9, and Lille score after 7 days of corticosteroid treatment was 0.021. Steroid therapy was continued, with an increase in serum creatinine levels. A diagnosis of AKI was made, and the patient was started on hemodialysis. Hallucinations started a few days after the initiation of hemodialysis. The differential diagnosis panel included hepatic, uremic, and Wernicke encephalopathies, which were deemed unlikely based on normal serum ammonia levels, unchanged status on hemodialysis, and absence of ataxia, nystagmus and confabulation, respectively. The patient was subsequently transferred to the intensive care unit, where the hallucinations were successfully treated with benzodiazepine therapy. Alcohol withdrawal syndrome was confirmed. A probable diagnosis of pre-renal injury was confirmed, although renal injury could not be ruled out.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), and dyslipidemia are among the most common metabolic disorders worldwide. Disruption of intestinal barrier integrity, as reflected by elevated zonulin levels, has been implicated in insulin resistance and lipid metabolism disorders, contributing to the pathogenesis of MASLD.

Aims & Methods

The aim was to evaluate fecal zonulin levels in patients with dyslipidemia and MASLD, and to explore their potential role as risk factors for disease development and progression. The study included 342 patients with dyslipidemia, among whom MASLD was diagnosed in 152 cases based on ultrasound and steatometry findings. Fecal zonulin levels were measured by ELISA. Small intestinal bacterial overgrowth (SIBO) was diagnosed using hydrogen breath testing. Correlations between zonulin, inflammatory markers (high-sensitivity C-reactive protein, hsCRP), lipid profiles, and SIBO prevalence were analyzed.

Results

SIBO was detected in 45% of patients with dyslipidemia and 53.2% of patients with MASLD. Fecal zonulin levels in patients with MASLD (115±2.76 ng/g) significantly exceeded the normal upper limit (≤107 ng/g) and were higher compared to patients without steatosis. Zonulin levels positively correlated with hsCRP (r=0.65, p<0.05) and triglycerides (r=0.58, p<0.05). A strong negative correlation was observed between SIBO presence and HDL-C levels (r=–0.78, p<0.05) in patients with dyslipidemia.

Conclusion

Elevated zonulin levels and increased intestinal permeability are closely associated with systemic inflammation and lipid metabolism disturbances in MASLD. Zonulin and SIBO may represent novel therapeutic targets for the prevention and treatment of MASLD and metabolic disorders.

Introduction

Functional dyspepsia (FD) is a common gastrointestinal disorder with limited treatment options. Itopride, a compound that combines dopamine D2 receptor antagonism with inhibition of acetylcholinesterase, may offer benefits over other prokinetics.

Aims & Methods

This meta-analysis evaluates the therapeutic efficacy of Itopride compared to placebo and other prokinetic agents in managing FD symptoms.
A total of 19 randomized controlled trials were included in the analysis, comprising six placebo-controlled studies (n=1981, 976 on placebo and 1005 on Itopride) and 13 trials comparing Itopride to another prokinetic (n=1077, 515 on Itopride and 562 on control prokinetics including mosapride citrate, levosulpiride, metoclopramide, domperidone, and cisapride). Meta-analyses were conducted using a random-effects (DerSimonian and Laird) model. Outcome measures included overall responder rate and symptom assessment, comparing Itopride to 1) all prokinetics and 2) placebo. In addition, Itopride was compared to placebo and domperidone for symptom scores of epigastric pain and early satiation. Results are presented as Cohen’s d (95% CI) or odds ratios(OR) (95% CI).

Results

Analysis of responder rates from seven placebo-controlled and nine active comparator studies showed a statistically significant benefit of Itopride over placebo (OR=1.25, 1.07 to 1.45, p=0.01), with no significant difference when compared to other prokinetics (OR=1.11, 0.93 to 1.34).
When assessing overall symptom scores, three placebo-controlled and four prokinetic-controlled trials were analyzed. Itopride showed a moderate effect size compared to other prokinetics (Cohen’s d=0.51, 0.13 to 0.88, p=0.01) and a large but not statistically significant effect compared to placebo (Cohen’s d=1.14, -0.43 to 2.71).
Early satiation was assessed in six domperidone-controlled trials, yielding a significant odds ratio of 1.37 (1.02 to 2.67, p=0.04). A large but not statistically significant difference was found compared to placebo (two trials, Cohen’s d=1.10, -0.47 to 2.67). For epigastric pain, a moderate but not statistically significant difference was found with placebo (two trials, Cohen’s d=0.68, -0.01 to 1.38) or domperidone (four trials, OR=0.85, 0.63 to 1.16).

Conclusion

This meta-analysis suggests that Itopride provides significant symptom relief in patients with FD compared to placebo, particularly in overall responder rates. While Itopride’s benefits over other prokinetics were modest in general symptom relief, it demonstrated a statistically significant advantage over domperidone for early satiation.

Introduction

The highest risk factor of inflammatory bowel disease (IBD) is having a first-degree relative (FDR) with IBD. However, genetic variation accounts for only a small proportion of IBD heritability. Evidence from family and twin studies underscores the role of shared environment for the development of IBD. In a recent study based on two population-based IBD cohorts from South-Eastern Norway, thirty years apart, we reported a substantial increase in the rate of familial IBD (1).

Aims & Methods

This study investigates the potential underlying mechanisms for the increased rate of familial IBD in South-Eastern Norway.
We examine the association between shared environment and gene expression across IBD phenotypes [Crohn’s disease (CD) and ulcerative colitis (UC)] and four comparison groups: (I) multiplex IBD familial patients (≥3 FDRs with IBD), (II) healthy relatives in multiplex IBD families, (III) sporadic IBD patients, and (IV) symptomatic non-IBD controls. Expression analyses focus on four candidate genes, FKBP5, BCL3, VMP1, and TRAIL, previously identified as differentially methylated in IBD compared to controls (2,3). Blood samples were collected from 15 multiplex IBD families in South-Eastern Norway, between April 2023 and January 2024. For comparison, blood samples from 50 sporadic IBD patients and 50 symptomatic controls (SC) were obtained from the IBSEN III cohort (4).
RNA was extracted from PAXgene blood samples of the multiplex families at EpiGen, Akershus University Hospital, Norway, while RNA extractions from the sporadic IBD patients and SCs were performed at The Institute of Clinical Molecular Biology, Kiel, Germany. All cDNA synthesis were carried out at EpiGen. Gene expression was measured using RT-qPCR on cDNA with target-specific primers. Relative quantification was performed using GAPDH and ACTB as housekeeping genes.
Simple t-tests were conducted to compare the mean gene expression between the four comparison groups and across IBD phenotypes.

Results

The multiplex IBD family study included 62 individuals, 41 IBD patients, 25 patients with UC, 16 with CD, and 21 healthy family members, 13 FDR and 8 spouses. The results for the differences in mean fold changes between the four groups, including CD and UC for each of the four candidate genes, are presented in Table 1. The gene expression analysis revealed differences in mean fold changes between the four groups and across CD and UC.
The relative quantification of gene expressions for the four candidate genes revealed no significant differences in gene expression among the IBD patients vs healthy members of multiplex families.
Significant differences were observed for all candidate genes among familial IBD vs sporadic IBD and between healthy multiplex family members vs symptomatic controls, except for BCL3 and TRAIL, respectively. (p<0.005).

Conclusion

Our results reveal associations between the expression levels of IBD candidate genes and shared family environment, suggesting that epigenetic mechanisms may contribute to the development of familial IBD. Further methylation studies are warranted to clarify the underlying mechanisms of changed gene expression.

References

1. Aabrekk TB. Increased familial risk of IBD over thirty years based on twopulation-based IBD incident cohorts conducted in South-Eastern Norway in 1990-1994 (IBSEN I) and in 2017-2019 (IBSEN III). [Abstract]. In press 2024.
2. Ventham NT, Kennedy NA, Adams AT, Kalla R, Heath S, O'Leary KR, et al. Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease. Nat Commun. 2016;7:13507.
3. Joustra V, Hageman IL, Satsangi J, Adams A, Ventham NT, de Jonge WJ, et al. Systematic Review and Meta-analysis of Peripheral Blood DNA Methylation Studies in Inflammatory Bowel Disease. J Crohns Colitis. 2023;17(2):185-98.
4. Kristensen VA, Opheim R, Perminow G, Huppertz-Hauss G, Detlie TE, Lund C, et al. Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway. Scand J Gastroenterol. 2021;56(8):899-905.

Disclosure

Vendel A. Kristensen har reported scientific advisory boards from Takeda AS, consultant fees from Janssen-Cilag AS and speaker fees from Thermo Fisher Scientific.
Marte Lie Høivik has reported investigator-initiated research grants from Takeda, Pfizer, Tillotts, Ferring and Janssen. Speaker honoraria from Takeda, Tillotts, Ferring, AbbVie, Pfizer, Galapagos, MSD and Meda and Advisory board Takeda, Galapagos, MSD, Lilly, Janssen, Pfizer and AbbVie.
The other authors of this abstract have no Conflict of Interest

Introduction

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) have gained attention for their role in managing type 2 diabetes and obesity. These drugs help regulate blood sugar levels and promote satiety. This effect benefits weight management, as it supports better control over eating habits and can lead to significant weight loss in some patients. In addition, recent studies showed promising influences on reducing alcohol consumption.

Aims & Methods

This systematic review assesses the impact of GLP-1 RA treatment on alcohol consumption behaviors. Following PRISMA guidelines, this study is conducted through a comprehensive search in PubMed, EMBASE, Scopus, Cochrane, and ClinicalTrials.gov up to February 1, 2025. It included participants with occasional or excessive alcohol use, focusing on self-reported intake, alcohol-related diagnoses, relapse rates, and neuroimaging. Data extraction and risk-of-bias assessments were independently performed by reviewers using the CASP tool, with both qualitative and quantitative synthesis of outcomes.

Results

Thirteen studies are included in this study with a sample size of 5,246,188 participants. The GLP-1 RAs consisted of Semaglutide, Exenatide, Liraglutide, Dulaglutide, and Tirzepatide. The overall mean alcohol intake decreased significantly from 11.8 ± 1.0 to 4.3 ± 0.5 units per week (p < 0.001) ¹. At week 12, participants in the dulaglutide group consumed approximately 29% less alcohol than those in the placebo group (adjusted relative effect = 0.71, 95% CI 0.52–0.97, P = 0.04) ². In contrast, a randomized controlled trial (RCT) involving Exenatide showed no difference in alcohol consumption (in grams) between the treatment and placebo ³. Additionally, two observational studies reported significant reductions in Alcohol Use Disorders Identification Test (AUDIT) scores with Semaglutide (B = -5.1, SE = 1.3, p < 0.001) and Tirzepatide (B = -6.7, SE = 1.3, p < 0.001) ^4,5. An additional observational study demonstrated a notable decrease in AUDIT-Consumption compared to unexposed individuals (DiD: 0.09 points, 95% CI: 0.03–0.14, p = 0.0025) ⁶. The CASP assessments rated most studies as moderate to high quality.

Conclusion

GLP-1 receptor agonists appear to offer a promising, effective, and well-tolerated pharmacological approach for reducing alcohol consumption and preventing relapse in alcohol use disorder (AUD). Further large-scale randomized trials are required to confirm their efficacy and guide clinical practice.

References

1. O’Farrell M, Almohaileb FI, le Roux CW. Glucagon-like peptide-1 analogues reduce alcohol intake. Diabetes Obes Metab. 2025;27(3):1601-1604. doi:10.1111/DOM.16152
2. Probst L, Monnerat S, Vogt DR, et al. Effects of dulaglutide on alcohol consumption during smoking cessation. JCI Insight. 2023;8(22). doi:10.1172/JCI.INSIGHT.170419
3. Klausen MK, Jensen ME, Møller M, et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight. 2022;7(19). doi:10.1172/JCI.INSIGHT.159863
4. Quddos F, Hubshman Z, Tegge A, et al. Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. Scientific Reports 2023 13:1. 2023;13(1):1-12. doi:10.1038/s41598-023-48267-2
5. Richards J, Dorand MF, Royal K, Mnajjed L, Paszkowiak M, Simmons WK. Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. J Clin Psychiatry. 2023;85(1). doi:10.4088/JCP.23M15068
6. Farokhnia M, Tazare J, Pince CL, et al. Glucagon-like peptide-1 receptor agonists but not dipeptidyl peptidase-4 inhibitors reduce alcohol intake.

Disclosure

The authors declare no conflicts of interest regarding the publication of this abstract. All findings and conclusions are the authors' own and do not represent the views of any funding organizations or institutions.