Introduction

Advanced chronic liver disease (ACLD) may present in different stages with distinct prognoses. Child-Pugh and MELD scores are commonly used models for predicting liver-related mortality and decompensation, but they have several limitations. An alternative or complementary tool that is simple and cost-effective would be invaluable. Recently, some studies identified a potential role of ammonia in predicting liver-related outcomes.

Aims & Methods

Our primary objective was to explore the predictive role of plasma ammonia levels regarding liver-related complications and mortality. Our secondary aim was to validate a new measure that corrects baseline ammonia levels to the upper limit of normal (AMM-ULN) and test a cut-off which was proposed in the literature to define patients at higher risk of such outcomes (AMM-ULN ≥ 1.4).
This retrospective study included 278 patients with ACLD who had an ammonia measurement in our hospital between 2018 and 2022. ACLD patients were divided into compensated and decompensated stages, with the latter being subdivided into three stages, according to the type of decompensation. Outcomes of liver-related decompensation and mortality were assessed in each group. AMM-ULN was evaluated as a predictor of these outcomes both in compensated and decompensated patients. The predictive accuracy of AMM-ULN was then determined by identifying the best cut-off.

Results

Plasma ammonia levels and AMM-ULN were predictors of hepatic decompensation (HR = 1.453, 95%CI 1.085 – 1.945, p = 0.012) and mortality (HR = 1.010, 95%CI 1.003 – 1.017, p < 0.001) at 12 months, in the compensated patient group. The AUROC for AMM-ULN was 67.4% in 1-year decompensations and 69.5% in 1-year mortality, with similar results for ammonia levels. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months (p = 0.009 and p = 0.020, respectively).

Conclusion

Both ammonia levels and AMM-ULN were predictors of hepatic decompensation and liver-related mortality in compensated patients, at 12 months of follow-up. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months.

References

D’Amico, G., Garcia-Tsao, G., & Pagliaro, L. (2006). Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. Journal of Hepatology, 44(1), 217–231. https://doi.org/10.1016/j.jhep.2005.10.013
Haj, M., & Rockey, D. C. (2018). Predictors of clinical outcomes in cirrhosis patients. Current Opinion in Gastroenterology, 34(4), 266–271. https://doi.org/10.1097/MOG.0000000000000450
De Franchis, R. et al (2022). Baveno VII – Renewing consensus in portal hypertension. Journal of Hepatology, 76(4), 959–974. https://doi.org/10.1016/j.jhep.2021.12.022
Shalimar, Sheikh, M. F. et al (2019). Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology, 70(3), 982–994. https://doi.org/10.1002/hep.30534
Tranah, T. H. et al (2022). Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis. Journal of Hepatology, 77(6), 1554–1563. https://doi.org/10.1016/j.jhep.2022.07.014
Balcar, L. et al (2023). Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease. JHEP Reports, 5(4), 100682. https://doi.org/10.1016/j.jhepr.2023.100682
Elzeftawy, A. et al (2018). Evaluation of the blood ammonia level as a non-invasive predictor for the presence of esophageal varices and the risk of bleeding. The Turkish Journal of Gastroenterology. https://doi.org/10.5152/tjg.2018.17894

Introduction

Filgotinib is a selective JAK1 inhibitor recently licensed for use in moderate-severe Ulcerative Colitis (UC)​¹​​​​.

Aims & Methods

We sought to review outcomes for patients commenced on Filgotinib for UC in the Glasgow South Sector IBD Service. Patients were identified using the local IBD Biologics Database. Electronic patient records were reviewed for demographics, previous treatment, and outcomes since commencing Filgotinib.

Results

28 patients were commenced on filgotinib between July 2022 and February 2023. 21.4% were female and 78.6% male with a median age of 38y. By Montreal classification, 3.6% were classified as E1, 64.3% as E2 and 32.1% as E3. 50% of patients were biologic naïve with 71.4% on concomitant treatment with aminosalicylate. Median follow-up was 4 months.
78.6% (22/28) reported improvement in their symptoms with only 21.4% (6/28) experiencing side effects (SEs). 64.3% in the biologic-naïve group found subjective improvement in symptoms with 85.7% noting improvement in the biologic-experienced group. SEs included infections (3), Increase in cholesterol/triglycerides (2) and subjective worsening of low mood (1).
17 Patients had pre and post-treatment Faecal calprotectin (FC) available. Of those patients, 70.6% had an improvement with an overall reduction in median FC level from 1567 to 203 across the group. This reduction did not reach statistical significance.
7/28 patients required a course of rescue steroids after starting treatment. No patients required IP admission since commencing treatment. 5/28 were considered to have a primary non-response to Filgotinib. Of these, 4 were switched to alternative advanced therapies and 1 awaits surgery.

Conclusion

Filgotinib appears a safe and effective treatment in moderate-severe UC for both biologic-naïve and experienced patients. Its oral route of administration and quick onset mechanism of action make it an appealing choice. Further real-world data is required with larger patient cohorts to establish its true utility in routine clinical practice.

References

1. D’Amico, F. et al. (2021) “Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis,” Journal of Crohn’s and Colitis, 16(5), pp. 835–844. Available at: https://doi.org/10.1093/ecco-jcc/jjab206.

Introduction

Filgotinib (FIL) is a once-daily, oral, Janus 1 kinase preferential inhibitor approved for the treatment of ulcerative colitis (UC) in Europe and Japan. The efficacy and safety of FIL in patients with moderately to severely active UC was evaluated in the phase 2b/3 randomized, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522).¹

Aims & Methods

This post hoc analysis aimed to identify characteristics of FIL-treated patients that were associated with achieving corticosteroid (CS)-free remission. Adults aged 18–75 years were randomized 2:2:1 to induction FIL 100 mg, FIL 200 mg or PBO once daily for 11 weeks in induction study A (biologic-naive) and B (biologic-experienced). At week 10, patients in clinical remission or with a Mayo Clinic Score (MCS) response were re-randomized 2:1 to continue their FIL regimen or PBO for 47 weeks in the maintenance study. This analysis included only data from patients receiving CSs at baseline. Using univariate logistic regression, we analysed characteristics associated with achieving clinical remission at week 58 without using CSs for UC over a continuous period of ≥6 months (CS-free remission). P values <0.05 were considered statistically significant.

Results

At baseline, 81, 37, 92 and 47 patients were receiving CSs in the maintenance FIL 100 mg (n=172), PBO-to-match (PTM) FIL 100 mg (n=89), FIL 200 mg (n=199) and PTM FIL 200 mg (n=98) groups, respectively. The rates of CS-free remission in the FIL 100 mg, PTM FIL 100 mg, FIL 200 mg and PTM FIL 200 mg groups were 13.6%, 5.4%, 27.2% and 6.4%, respectively. Age, body mass index, history of pancolitis, duration of UC, faecal calprotectin and C-reactive protein levels, MCS and concomitant use of systemic CSs, immunomodulators and aminosalicylates had no significant effect on CS-free remission in the FIL 200 mg group. Mean baseline Robarts Histopathology Index (RHI) (odds ratio [OR]=0.949, p=0.023) was significantly associated with 6-month CS-free remission in the FIL 200 mg group. A baseline Mayo endoscopic subscore (MES) of 2 (vs 3) was associated with significantly increased odds of 6-month CS-free remission in the FIL 200 mg and FIL 100 mg groups (Table). Being male, a former (vs current) smoker or biologic-experienced was associated with significantly reduced odds of 6-month CS-free remission in the FIL 200 mg group.

Table. Association between 6-month CS-free clinical remission (dependent variable) and baseline characteristics^a by treatment groups.

Conclusion

Most baseline characteristics analysed had no statistically significant effect on 6-month CS-free remission under FIL 200 mg treatment. Low baseline MES and RHI, female sex, being a current (vs former) smoker and biologic-naive may predict higher likelihood of sustained CS-free remission in patients receiving FIL 200 mg.

References

1. Feagan BG et al. Lancet 2021;397:2372–84.

Disclosure

TK has served as an advisory board member, consultant or speaker for AbbVie, Activaid, Ajinomoto Bio-Pharma, Alfresa Pharma, Astellas Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, JMDC, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical, and has received research funding from AbbVie, Alfresa Pharma, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical.
AD reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Abivax, AbbVie, Arena Pharmaceuticals, Falk Foundation, Gilead/Galapagos, Janssen and Pfizer; consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, MSD, Pfizer, Pharmacosmos, Roche/Genentech, Sandoz/Hexal, Takeda, Tillotts, and Vifor Pharma; payment from lectures, including service on speakers bureaus from AbbVie, Biogen, Celltrion, the Falk Foundation, Ferring Pharmaceuticals, Gilead/Galapagos, High5ImmunoTV, Janssen Pharmaceuticals, MSD, Pfizer, Takeda, Tillotts Pharma and Vifor Pharma; and payment for manuscript preparation from the Falk Foundation, Takeda, Thieme Medical Publishers and UNI-MED Verlag.
XR has served as an advisory board member, consultant or speaker for AbbVie, Amgen, Biogen, Celltrion, Ferring Pharmaceuticals, Galapagos NV, Janssen Pharmaceuticals, MSD, Pfizer, Sandoz and Takeda.
YF is an employee of Gilead Sciences K.K.
AO is an employee and shareholder of Galapagos NV.
CJ is a contractor for Galapagos NV.
TH has received lecture fees from Aspen Japan K.K., Janssen Pharmaceuticals, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical Co., Ltd., Pfizer and Takeda; research grants from AbbVie GK, Activaid, Alfresa Pharma Corporation, Bristol Myers Squibb, Eli Lilly Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Inc., Janssen Pharmaceutical K.K., JMDC Inc., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc. and Takeda; scholarship contributions from Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co., Ltd. and Zeria Pharmaceutical Co., Ltd.; and study group sponsorship from AbbVie GK, EA Pharma Co., Ltd., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Otsuka Holdings and Zeria Pharmaceutical Co., Ltd.
This study was funded by Gilead Sciences K.K.
The SELECTION trial was sponsored by Gilead Sciences Inc (Foster City, CA, USA). Galapagos NV (Mechelen, Belgium) was a collaborator for the SELECTION trial.
Writing support for the development of this abstract was provided by Tamsyn Stanborough, PhD, and Georgii Filatov of Oxford PharmaGenesis, Melbourne, Australia, and funded by Gilead Sciences K.K.

Introduction

Hypermobile Ehlers-Danlos syndrome (hEDS) is a hereditary non-inflammatory disorder of connective tissue laxity characterized by joint hyperextensibility in association with musculoskeletal symptoms. The prevalence of gastrointestinal (GI) symptoms, such as abdominal pain, nausea, and constipation is high in hEDS. Research on the relationship between EDS and GI symptoms has mostly been restricted to disorders of the gut-brain axis, whereas the relationship between hEDS and GI dysmotility remains to be clarified.

Aims & Methods

This study aimed to explore antro-duodenal manometry (ADM) patterns in patients with hEDS presenting with GI symptoms.

In a prospective open-label study, patients with hEDS and GI symptoms presumed to be the results of GI dysmotility underwent a 6-hour high resolution ADM. The manometry tracings were analyzed by two investigators (KS and JC) independently. Antral contraction frequency (contractions per minute) < 1.0 was considered as antral hypomotility. Pylorospasm was defined as isolated pyloric pressure waves within 60 minutes postprandial. The following neuropathic enteric patterns were scored: presence of retrograde peristalsis, bursts, clustered contractions, and absence of phase III contractions. Abnormal ADM was defined as having antral hypomotility and/ or pylorospasm and/ or neuropathic enteric patterns.

Results

Fifty patients (48 women, mean age 30.4 ± 11.1 yrs.) were included. At baseline, 74% of patients were dependent on enteral feeding and the mean BMI was 20.4 ± 4.4 kg/m².
Overall, ADM tracings with one or more abnormal patterns were identified in 53% of patients. Antral hypomotility and pylorospasm were detected in 29% and 15% of patients, respectively. Neuropathic enteric patterns were only seen in 17% of patients. In all cases, no more than one neuropathic pattern was identified. Among the observed neuropathic enteric patterns, 15% of patients showed retrograde peristalsis, 13% absence of phase III contractions, and 2% bursts. Clustered contractions were not identified in this cohort.

Conclusion

Hypermobile Ehlers-Danlos patients presenting with gastrointestinal symptoms showed low numbers of abnormal ADM patterns. In particular, enteric dysmotility was observed in only a small minority of cases. Antroduodenal dysmotility therefore does not appear to be a principle pathomechanism in the majority of hEDS cases studied. Further research is needed to understand the mechanisms that underlie GI symptom generation in this population.

Introduction

Endoscopic sleeve gastroplasty (ESG) is established as effective and mini-invasive procedure for obesity. Patients undergoing bariatric procedures in 80% of the cases are females. It is known that gender plays a role in several metabolic networks related to obesity; however no studies have investigated the gender impact on obesity after ESG.

Aims & Methods

To evaluate the gender impact on long-term weight loss outcomes after ESG in patients treated in our bariatric unit. We analyzed 160 patients that underwent ESG at Fondazione Policlinico Gemelli IRCCS from mese 2017 to mese 2021. A matched-pair analysis between the two groups for baseline BMI, age, and timing of the procedure was done. Weight loss outcomes were described in terms of total body weight (TBWL%) and excess weight loss (EWL%) at 12, 24 and 30 months.

Results

We found that men presenting for ESG had a higher body mass index (BMI) than women (40,7 kg/m² vs 39,8 kg/m²). After ESG the TBWL% in female at 12, 24, and 30 months was 17,2%, 14,0% and 15,2% compared to 14,9%, 14,3% and 9,6% in men, respectively. The EWL% was 48,4%, 39,6% and 41,7%, compared to 41,9%, 39,5% and 24,3% in men, respectively.

Conclusion

Women have more durable weight loss compared to men. More in depth studies are needed to understand the cause of this difference.