Introduction

Delivering effective secondary preventive and integrated care has the potential to break the revolving-door phenomenon of frequent readmissions in patients with advanced chronic liver disease. To address this, we launched the Care Coordination of Liver Disease (CCoLD) pilot, a novel nurse-led cirrhosis clinic in Western Sydney.

Aims & Methods

Following an index presentation to Blacktown or Mount Druitt hospitals (BMDH), patients (n=89, matched by age, sex, and MELD-NA liver disease severity score) were either followed up by the CCoLD clinical nurse consultant (intervention cohort) or received standard care (control cohort). Controlled evaluation of the impact of the nurse led clinic was carried out for a 3-month period including readmission rates and survival.

Results

The inaugural nurse led clinic led to a remarkable improvement in patient-level outcomes including a reduction in unplanned liver-related readmissions (2.08% for intervention cohort vs 12.2% for control cohort, p<0.01), and mortality at 30 days (0% for intervention cohort vs 7.3% for control cohort, p=0.03). Similar trends were observed at 90 days from index discharge. No deaths were observed in the intervention cohort as compared to the control cohort at 90 days (0% versus 7.3%, p=0.03), while unplanned liver-related readmissions were 19.5% for the control cohort vs 10.41% for the intervention cohort (p=0.115). Moreover, a longer time was required for emergency readmissions among the intervention cohort. Our nurse-led cirrhosis clinic was cost-effective with the number needed to treat (NNT) of 10 to prevent 1 readmission within 30 days or 4 over the entire study period to prevent 1 readmission.

Conclusion

These findings highlight the significant impact of optimised care-coordination. Post-discharge follow-up and education through a nurse-led clinic delivers goal-directed, and cost-effective secondary prevention and care. A multicentre randomised trial for wider evaluation of these findings is warranted.

References

1.AIHW. Australian Government, Australian Burden of Disease Study 2022: Australian Institute of Health and Welfare; 2022 [updated 13 December 2022].
2.Powell EE, Skoien R, Rahman T, Clark PJ, O'Beirne J, Hartel G, et al. Increasing Hospitalization Rates for Cirrhosis: Overrepresentation of Disadvantaged Australians. EClinical Medicine. 2019;11:44-53.
3. Volk ML, Tocco RS, Bazick J, Rakoski MO, Lok AS. Hospital readmissions among patients with decompensated cirrhosis. Am J Gastroenterol. 2012;107(2):247-52.
4.Tapper EB, Halbert B, Mellinger J. Rates of and Reasons for Hospital Readmissions in Patients With Cirrhosis: A Multistate Population-based Cohort Study. Clin Gastroenterol Hepatol. 2016;14(8):1181-8 e2.
5.Bajaj JS, Reddy KR, Tandon P, Wong F, Kamath PS, Garcia-Tsao G, et al. The 3-month readmission rate remains unacceptably high in a large North American cohort of patients with cirrhosis. Hepatology. 2016;64(1):200-8.
6.Wundke R, McCormick R, Narayana SK, Sorensen L, Wigg A. The Chronic Liver Disease Nurse Role in Australia: Describing 10 Years of a New Role in Cirrhosis Management. Gastroenterol Nurs. 2020;43(1):E9-E15.
7.Sherbuk JE, McManus KA, Kemp Knick T, Canan CE, Flickinger T, Dillingham R. Disparities in Hepatitis C Linkage to Care in the Direct Acting Antiviral Era: Findings From a Referral Clinic With an Embedded Nurse Navigator Model. Front Public Health. 2019;7:362.

Introduction

We evaluated celiac disease (CeD)-related symptoms and comorbidities in two US healthcare databases after CeD diagnosis according to the presence/absence of CeD-related symptoms or comorbidities before diagnosis.

Aims & Methods

This matched case–control study used data from two US healthcare databases: 1) MarketScan^® Commercial and Medicare Supplemental database (collection period: 2002−2023); 2) Optum Clinformatics^® Data Mart (Optum CDM; collection period: 2007−2023). Patients with CeD had ≥ 1 inpatient or ≥ 2 outpatient International Classification of Diseases (ICD)-9 or -10 codes (579.0 and K90.0, respectively) at any time during the collection period. Patients were matched in a 1:5 ratio with controls without CeD (no CeD ICD-9/-10 codes at any time during data collection) for age at diagnosis, sex, region, and diagnosis year. All individuals had continuous medical and pharmacy enrollment for 2 years pre/post CeD diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for symptoms/comorbidities after CeD diagnosis were estimated by generalized multivariate logistic regression comparing cases vs matched controls stratified by those with (persistent) or without (new-onset) the relevant symptom/comorbidity pre-diagnosis. Symptoms assessed included abdominal pain, bloating, diarrhea, headache, nausea/vomiting, and tiredness. Comorbidities assessed included depression/anxiety, irritable bowel syndrome (IBS), and iron deficiency anemia (IDA).

Results

The numbers of CeD cases and controls were 39,814 and 198,961 in MarketScan, and 18,357 and 91,754 in Optum CDM, respectively. In both databases, CeD diagnosis was significantly positively associated with having CeD-related symptoms/comorbidities 2 years after CeD diagnosis regardless of pre-diagnosis status; and the strengths of associations were greater among patients with new-onset than with persistent symptoms/comorbidities after CeD diagnosis.
In MarketScan, the ORs (95% CI) in patients with new-onset symptoms were highest for bloating (7.98 [7.32–8.71]), diarrhea (6.83 [6.48–7.19]), and nausea/vomiting (3.75 [3.49–4.04]), and in those with new-onset comorbidities for IBS (8.30 [7.65–9.00]), IDA (6.35 [5.94–6.79]), and depression/anxiety (2.12 [2.04–2.20]). The ORs (95% CI) in patients with persistent symptoms were 2.47 (1.86–3.27) for bloating, 2.47 (2.21–2.76) for diarrhea, and 2.46 (2.05–2.96) for nausea/vomiting, and in those with persistent comorbidities were 1.38 (1.16–1.64) for IBS, 1.93 (1.70–2.18) for IDA, and 1.42 (1.34–1.51) for depression/anxiety.
In Optum CDM, the ORs (95% CI) in patients with new-onset symptoms were highest for bloating (6.15 [5.56–6.80]), diarrhea (5.85 [5.48–6.24]), and nausea/vomiting (3.38 [3.08–3.70]), and in those with new-onset comorbidities for IBS (6.17 [5.56–6.85]), IDA (5.31 [4.89–5.77]), and depression/anxiety (2.10 [1.99–2.21]). The ORs (95% CI) in patients with persistent symptoms were 2.25 (1.70–2.97) for bloating, 2.51 (2.22–2.84) for diarrhea, and 2.77 (2.23–3.43) for nausea/vomiting, and in those with persistent comorbidities were 1.40 (1.15–1.71) for IBS, 2.54 (2.17–2.97) for IDA, and 1.50 (1.38–1.62) for depression/anxiety.

Conclusion

CeD diagnosis was significantly associated with having CeD-related symptoms/comorbidities 2 years after CeD diagnosis, with greater associations among patients with new-onset symptoms/comorbidities than those with persistent symptoms/comorbidities. These results emphasize the clinical burden of CeD and the need for improved treatment options.

Disclosure

FZ has served as a speaker for Werfen and a consultant for Takeda. MA, SM, VG, SG, IP, NC, and DAL are employees and shareholders of Takeda Development Center Americas, Inc. and receive stock or stock options. BL has nothing to disclose.

Introduction

Dientamoeba fragilis is a protozoan of the human digestive tract, yet its pathogenic role remains poorly understood. Fecal microbiota transplantation (FMT) provides a useful model for investigating the potential pathogenicity and transmission of this protist from donor to recipient. Donor selection is highly stringent, and the presence of D. fragilis is subject to controversy as an exclusion criterion [1-4].

Aims & Methods

This study aimed to determine the prevalence of D. fragilis in both FMT donors and recipients and to evaluate its potential impact on the efficacy and safety of FMT as a treatment for recurrent Clostridioides difficile infection (rCDI). This single-center, longitudinal cohort study analyzed stool samples from FMT donors and recipients at three time points: pre-treatment and at 2 and 8 weeks post-FMT. All samples were negative for D. fragilis on direct microscopy and were retrospectively tested using real-time (RT-PCR). CDI cure rates, gastrointestinal adverse events (AE), and serious adverse events (SAE) were assessed prospectively.

Results

A total of 53 FMT were administered to 47 different patients, with 23 of 53 (43%) derived from D. fragilis-positive donor stool (4 out of 10 donors, 40%). One recipient tested positive before FMT (1/47, 2.1%). Among 22 patients initially negative for D. fragilis who received stool from D. fragilis-positive donors, four (18.2%) tested positive on day 15 post-FMT and remained positive at week 8. None of the recipient with D. fragilis-negative FMT was tested positive. No significant differences in efficacy, AE, or SAE were observed between recipients of FMT from D. fragilis-positive versus -negative donors, even in severely immunocompromised patients. No SAE could be attributed to FMT.

Conclusion

This study suggests that D. fragilis can be transmitted through FMT without significant clinical impact in terms of efficacy and safety. These findings argue for reconsidering the exclusion of positive donors and support the lack of pathogenicity of D. fragilis.

References

1. Hall LM, Munasinghe VS, Vella NGF, Ellis JT, Stark D. Observations on the transmission of Dientamoeba fragilis and the cyst life cycle stage. Parasitology 2024 ; 151:337–345.
2. Cacciò SM. Molecular epidemiology of Dientamoeba fragilis. Acta Trop 2018 ; 184:73–77.
3. Shasha D, Grupel D, Treigerman O, et al. The clinical significance of Dientamoeba fragilis and Blastocystis in human stool—retrospective cohort study. Clin Microbiol Infect 2024 ; 30:130–136.
4. Terveer EM, Gool T van, Ooijevaar RE, et al. Human Transmission of Blastocystis by Fecal Microbiota Transplantation Without Development of Gastrointestinal Symptoms in Recipients. Clin Infect Dis 2019 ; 71:2630–2636.

Introduction

Treatment strategy of hepatocellular carcinoma (HCC) is a complex decision-making process that considers several variables in clinical practice. A “multiparametric therapeutic approach” has been proposed (Lancet Oncol 2023): the feasibility of all treatments is evaluated systematically in a hierarchical order, to match each patient with the optimal therapy.

Aims & Methods

The aim of the study is to validate the reliability of the new multiparametric decisional framework (MPDF) and the impact of the different variables included in the framework on the final treatment decision in clinical practice. This is a prospective ongoing study with a first monocentric phase (A) and a second multicentric validation phase. Primary endpoints are: 1) adherence to MPDF for treatment allocation, 2) identification of the relative weight of variables involved in this MPDF for treatment decision, while secondary endpoints are overall survival and radiological response after treatment. The study includes all consecutive patients with HCC managed in each center from September 1^st, 2023. The disease is staged according to Barcelona Clinic Liver Cancer (BCLC) classification, while patient’s characterization is conducted by Charlson Comorbidity Index (CCI), Liver Frailty Index (LFI), Child-Pugh (CPT) and ALBI, MELD and skeletal muscle mass index by CT. Each patient is allocated to treatment according to MPDF, BCLC 2022 was the benchmark.

Results

As of November 1st, 2023, 48 patients were recruited into phase A of the study [median age 70 (52-87) years, 81% male, 37% HCV, 27% first treatment for HCC]. Thirteen (27%) patients were classified BCLC 0, 17 (35%) A, 6 (12.5%) B, 6 (12.5%) C and 6 (12.5%) D. The median CCI was 8 (4-13), the median LFI was 4.15 (2.99-4.81). Thirty-nine (81%) patients were in CPT class A, 7 (15%) in B and 2 (4%) in C, while 32 (67%) were classified ALBI grade 1 and 16 (33%) ALBI grade 2, and the median MELD score was 8.5 (6-22). Forty-four (92%) patients received treatment through a multidisciplinary team (MDT). According to the MPDF, 9 (19%) patients were allocated to liver transplant, 5 (10%) to laparoscopic surgical resection, 10 (21%) to microwave thermal ablation (MWTA), 7 (15%) to transarterial treatments (4 TACE and 3 TARE), 3 (6%) to other locoregional therapies (2 MWTA+TACE and 1 electrochemotherapy), 6 (13%) to systemic treatment and 5 (10%) to palliative care only. In 4 cases, the MDT decided for reassessment at 3 months. The treatment allocation was coherent to the BCLC 2022 in 69% BCLC 0, 82% BCLC A, 83% BCLC B, 67% BCLC C and 100% BCLC D.

Conclusion

Preliminary data of our ongoing prospective study suggest that personalized approach for HCC treatment by MPDF is feasible in clinical practice and might help ensuring a customized approach in a standardized framework. Updated data will be presented at the meeting.

Introduction

Alcohol use disorder (AUD) remains a significant global health concern. Despite the availability of various pharmacological and behavioural interventions, alcohol-related mortality is rising.

Aims & Methods

This systematic review aimed to critically evaluate the existing literature on the role of glucagon-like peptide receptor 1 analogues (GLP-1 RAs) in people with AUD.
Electronic search was conducted on Ovid Medline, EMBASE, Cochrane Central and PsycINFO from inception to March 2024. Grey literature was searched. The primary outcome of the review was to explore the impact of GLP-1 RAs on self-reported alcohol intake in people with AUD. The extracted data were organized and synthesized to identify key findings and trends evaluating the potential impact of GLP-1 RAs on alcohol consumption in AUD. Narrative synthesis was done to provide a coherent and detailed narrative of the evidence, highlighting significant findings, relationships, and implications. PROSPERO (CRD42024531982).

Results

Seven studies comprising 88,163 participants were included; of these, 38,746 (43.9%) were treated with GLP-1 RAs. Pooled mean age was 49.6 years (SD=10.5), 56.9% (n=50,151/88157) were male, and if the study provided ethnicity 87.5 % (n=426/487) were white. An RCT comparing exenatide with placebo found no significant difference in self-reported alcohol measures at 26 weeks (percentage point reduction: heavy drink days: 6.0, 95% CI -7.4 to 19.4, p=0.37; total alcohol consumption: -42.0 g/30 days, 95% CI -507.7 to 423.7, p=0.86; days without alcohol use: -10.5, 95% CI -2.6 to 23.4, p=0.11). But in participants (n=30) with BMI > 30 kg/m², exenatide compared with placebo was associated with a significant reduction in heavy drinking days (percentage point reduction 23.6, 95% CI, –44.4 to –2.7, P=0.034) and in total alcohol consumed (-1,205 g, 95% CI, –2,206 to –204, P= 0.026). Another RCT showed dulaglutide users compared to placebo were 29% more likely to reduce weekly alcohol consumption (relative effect size: 0.71, p=0.04). In an observational study, authors reported with liraglutide (n=42) 21.4% stopped and 78.6% reduced drinking (p<0.05). A prospective cohort control study showed people on semaglutide or tirzepatide (n=153) compared to no medication significantly reduced number of alcoholic drinks consumed and binge drinking (p<0.05). In a case series (n=6) semaglutide use was associated with a 9.5-point reduction in alcohol use disorder identification test score. A population-based study from Denmark (n=87,676) reported that at 90 days people on GLP-1 RAs compared to one on dipeptidyl peptidase-4 inhibitors (DPP-4) were less likely to experience alcohol-related events ( HR 0. 46, 95% CI 0.24 to 0.86) and effect remained positive long term (356-4619 days: HR 0.72, 95% CI 0.60–0.86). Two qualitative studies examining Reddit social media posts from people on GLP-1 RAs noted over two-thirds addressed a reduction in alcohol consumption. Functional brain imaging suggested significant reductions in cue reactivity were observed in the ventral striatum [F(1,31) = 4.744, P = 0.037, partial η2 = 0.133], dorsal striatum [F(1,31) = 6.124, P = 0.019, partial η2 = 0.165], and putamen [F(1,31) = 4.730, P = 0.037, partial η2 = 0.132] after 26 weeks of exenatide treatment compared with placebo (Table 1). Two studies were of high quality, two medium, and three low.

Conclusion

GLP-1 RAs show promise in reducing alcohol consumption and improving outcomes in individuals with AUD, although heterogeneous study findings warrant further research to establish true effectiveness and safety of GLP-1 RAs in AUD.

References

1. Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England). 2018;392(10152):1015-35.
2. Klausen MK, et al. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. British Journal of Pharmacology. 2022;179(4):625-41.
3. Klausen MK, et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight. 2022;7(19).
4. Probst L, et al. Effects of dulaglutide on alcohol consumption during smoking cessation. JCI Insight. 2023;8(22).
5. SANJAY KALRA BK, AMIT SHARMA. Change in Alcohol Consumption Following Liraglutide Initiation: A Real Life Experience. Clinical Diabetes2024.
6. Quddos F, et al. Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. Scientific Reports. 2023;13(1):20998.
7. Bremmer MP, Hendershot CS. Social Media as Pharmacovigilance: The Potential for Patient Reports to Inform Clinical Research on Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists for Substance Use Disorders. Journal of Studies on Alcohol and Drugs. 2023;85(1):5-10.
8. Wium-Andersen IK, et al Osler M. Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events. A nationwide register-based cohort and self-controlled case series study. Basic & Clinical Pharmacology & Toxicology. 2022;131(5):372-9.