Introduction

The incidence of type I gastric neuroendocrine neoplasms (gNEN) has increased substantially over the past 50 years, although studies evaluating the association with chronic autoimmune gastritis (AIG) in the long term have been inconsistent.

Aims & Methods

The main aim was to evaluate the incidence of type I gNENs in a cohort of AIG patients enrolled from October 2020 to May 2022, with a histologic diagnosis of CAAG; circulating levels of chromogranin A (CgA) and gastrin were assessed at enrollment. Included patients underwent regular endoscopic follow-up, to assess for gastric neoplastic lesions, enterochromaffin-like (ECL) cell hyperplasia, and the development of gNEN.

Results

We included 176 patients [142 women, median age 64 years (51-41)], diagnosed with AIG from January 1990 to June 2022. At enrollment, 116 patients (65.9%) had ECL hyperplasia, of which 29.5% had simple/linear, 30.7% had micronodular, and 5.7% had macronodular. The median follow-up was 5 years (3-7.5). After 1032 person-years, 33 patients developed a total of 33 gNEN type I, with an incidence rate of 0.032 person-years, corresponding to an annual cumulative incidence of 3.2%. Circulating gastrin levels were significantly higher in AIG patients who developed gNENs [median 992 pg/mL IQR=449-1500 vs 688 pg/mL IQR =423-1200, p=0.03]; similarly, circulating CgA levels were significantly higher in patients with gNENs [median 227 ng/mL IQR=124-421 vs 174 ng/mL IQR= 77-265, p=0.01].

Conclusion

Type I gNENs represent a non-negligible complication in patients with AIG, and they are related to hypergastrinemia. Also elevated circulating CgA levels are associated with the presence of gNENs.

References

1. Massironi S, Zilli A, Elvevi A,et al. The changing face of chronic autoimmune atrophic gastritis: an updated comprehensive perspective. Autoimmun Rev. 2019;18:215-22.
2. Rugge M, Bricca L, Guzzinati S, et al. Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients. Gut. 2023;72:30-8.
3. Shah SC, Piazuelo MB, Kuipers EJ, et al. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021;161:1325-32.
4. Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated Sydney System. Am J Surg Pathol. 1996;20:1161-81.
5. Delle Fave G, O'Toole D, Sundin A, et al. ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms. Neuroendocrinology. 2016;103:119-24.
6. Yue H, Shan L, Bin L. The significance of OLGA and OLGIM staging systems in the risk assessment of gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2018;21:579-87.
7. Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182-8.
8. Capurso G, Gaujoux S, Pescatori LC, et al. The ENETS TNM staging and grading system accurately predict prognosis in patients with rectal NENs. Dig Liver Dis. 2019;51:1725-30.

Introduction

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have been linked to gut dysbiosis.

Aims & Methods

This study aimed to investigate the relationship between gut microbiota composition, hepatic fat content and stiffness, and body mass index (BMI) status. This cross-sectional study enrolled adolescents aged 12 to 18. Transient elastography with controlled attenuation parameter (CAP) was employed to diagnose hepatic fibrosis and steatosis. Fecal samples were analyzed by 16S rRNA sequencing. Relative abundance, as well as alpha- and beta-diversity of the microbiota, were compared across participants with different nutrition statuses and the presence of hepatic steatosis and fibrosis.

Results

A total of 76 participants (51 males) were recruited for this study, including 43 with normal weight, 19 overweight, and 14 obese. The clinical characteristics of the participants are presented in Table 1. Hepatic steatosis was present in 8 out of 14 obese participants (57.2%) and 2 out of 19 overweight (10.5%) participants. Hepatic fibrosis was detected in 4 out of 14 obese participants (28.6%) but none in the normal weight or overweight groups. There were no significant differences in alpha- or beta-diversity between the normal weight, overweight, and obese groups. The Firmicutes to Bacteroidetes (F/B) ratio was 1.2 across all three groups. Several genera, including Eubacterium_halli_group and Ruminococcus_gauvreauii_group were present in higher abundances in the gut microbiome of the obese group compared to the normal-weight group, with p values of 0.025 and 0.036, respectively. In contrast, Bifidobacterium was more abundant in the normal-weight participants (p=0.012). Obese individuals with hepatic fibrosis exhibited a significantly higher F/B ratio compared to those without hepatic fibrosis (p=0.04). There were significant differences in the relative abundance of specific genera between the fibrosis and non-fibrosis groups: Phascolarctobacterium (p=0.020), Dorea (p=0.040), and Ruminococcus_gauvreauii_group (p=0.045) were present in higher abundances in the fibrosis group, whereas Senegalimassilia was more abundant in the non-fibrosis group (p=0.037).

Conclusion

Hepatic steatosis and fibrosis are common among obese adolescents. The gut microbiota abundance in obese individuals with hepatic fibrosis differ from those without it. Further studies are crucial to explore the role of gut microbiota modification in the progression of hepatic steatosis and fibrosis.

Introduction

In patients with Helicobacter pylori (HP) infection, superficial gastritis proceeds to atrophic gastritis in about half of the patients. Although, it usualy involves the antrum, it can also proceed to the corpus with sometimes neuroendocrine cell hyperlasia and chromogranin A antibody positivity, like in classic autoimmune gastritis.

Aims & Methods

The aim of our study was to determine the frequence of HP infection in autoimmune atrophic gastritis and its characteristics
A retrospective study was conducted over patients with autoimmune atrophic gastritis diagnosed in the gastroenterology department in Mohamed taher maamouri hospital between January 2019 and December 2021. Clinical, biological, endoscopic and pathology features were abstracted from medical records.

Results

A total of 31 patients were included in this study. The sex ratio M/F was 0.8 and the mean age was 56 years [28- 82 years]. The average haemoglobin level was 9,9 g/dl and the average mean corpuscular volume was 95,6 fL. Serum markers were available in 13 patients. Intrinsic factor antibodies were positive in five patient and anti-parietal cell antibodies in 11 patients. Pathology findings of fundal biopsies showed mild atrophy in 16,1% patients, moderate in 48,4% and severe in 35,5% with presence of intestinal metaplasia in 90,3%. The antrum was atrophic in one patient and antral intestinal metaplasia was detected in 11 patients (35,5%). HP infection was diagnosed in 23 patients (74,2%). The presence of HP infection was correlated with the severity of anaemia (p= 0.048). No correlation was found between HP infection and the degree of atrophy or the presence of intestinal metaplasia (p= 0.35 et 0.38 respectively).

Conclusion

Our study showed the presence of HP in 74.2% of patients with autoimmune atrophic gastritis , which may support the inplication of HP infection in the development of autoimmune gastritis. The presence of HP infection was correlated with the severity of anaemia, hence the importance of HP eradication treatment.

Introduction

The efficacy and safety of upadacitinib (UPA), an oral reversible Janus kinase inhibitor, were demonstrated for patients with Crohn’s disease (CD) in three phase 3 randomized, controlled, double-blind clinical trials: U-EXCEL (NCT03345849), U-EXCEED (NCT03345836), and U-ENDURE (NCT03345823).^1–3 UPA is approved for the treatment of moderately to severely active CD.^4,5 The STRIDE-II CD treat-to-target guidelines recommend using composite clinical and endoscopic treatment targets to improve patient outcomes.⁶ We assess the efficacy of UPA in patients with moderately to severely active CD using stringent, composite efficacy endpoints.

Aims & Methods

In two phase 3 induction studies, U‑EXCEL and U-EXCEED, patients were randomized 2:1 to receive once-daily UPA 45 mg or placebo (PBO) for 12 weeks. Those who achieved a clinical response (≥30% decrease in average daily very soft or liquid stool frequency [SF] and/or ≥30% decrease in average daily abdominal pain score [APS] and both not worse than baseline) to UPA were re-randomized 1:1:1 to receive UPA 15 mg, UPA 30 mg, or PBO in the 52-week U-ENDURE maintenance study. Five composite clinical and endoscopic endpoints were assessed at weeks 12 of induction and 52 of maintenance therapy: (1) enhanced clinical response (per very soft/liquid SF and APS) and endoscopic response; (2) clinical response (CR-100) and endoscopic response; (3) clinical remission per CD Activity Index (CDAI) and endoscopic response; (4) SF/APS clinical remission and endoscopic remission; and (5) CDAI clinical remission and endoscopic remission. Treatment group differences were compared using the Cochran-Mantel-Haenszel test, adjusted for stratification factors. Analyses used nonresponder imputation while incorporating multiple imputation to handle missing data due to COVID-19.

Results

A greater proportion of patients receiving UPA 45 mg vs PBO achieved stringent clinical and endoscopic endpoints at week 12: enhanced clinical response and endoscopic response (33.7 vs 6.1%); CR-100 and endoscopic response (27.8 vs 5.2%); CDAI clinical remission and endoscopic response (24.7 vs 5.2%); SF/APS clinical remission and endoscopic remission (15.7 vs 3.5%); and CDAI clinical remission and endoscopic remission (15.0 vs 3.7%; for all comparisons, nominal P values ≤ .001; Table). At week 52, a greater proportion of patients who received UPA 15 mg or UPA 30 mg achieved stringent clinical and endoscopic endpoints vs patients in the PBO group (Table). Composite endpoint achievement rates were numerically greater with UPA 30 mg than with UPA 15 mg (Table). The safety of UPA in CD was previously reported.^1–3
​

Conclusion

In both induction and maintenance studies, patients receiving UPA had greater achievement of stringent efficacy endpoints vs patients who received PBO. UPA 30 mg demonstrated numerically greater clinical and endoscopic efficacy vs UPA 15 mg. The largest differences between UPA and PBO treatment groups occurred for the enhanced clinical response and endoscopic response endpoint.

References

1. Colombel JF, et al. Gastroenterology. 2022;162(Suppl):1394.
2. Loftus EV Jr. United European Gastroenterol J. 2022;10(Suppl 8):103–104.
3. Panés J, et al. Am J Gastroenterol. 2022;117(Suppl):10.
4. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
5. RINVOQ. Summary of Product Characteristics. AbbVie Inc.; 2023. Accessed March 27, 2023. https://www.medicines.org.uk/emc/product/12830/smpc.
6. Turner D, et al. Gastroenterology. 2021;160(5):1570–1583.

Disclosure

SD has served as a speaker, consultant, and advisory board member for AbbVie, Actelion, Alfa Wasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson & Johnson, Millennium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, Schering-Plough, UCB Pharma, and Vifor.
BGF has consulted for AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, Avoro Capital Advisors, Atomwise,, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boxer, Celsius Therapeutics,Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium,, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, and Zealand Pharma; a speaker for AbbVie, Janssen, and Takeda; an advisor for AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer-Ingelheim, Celgene/BMS, Ecor1Capital, Eli Lilly, Genentech/Roche, GSK, Index, Janssen, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, REDX Pharma, Sanofi, Takeda, Teva, and Tillotts Pharma; a senior scientific director for Alimentiv Inc.; an employee of Western University; and holds stocks in Gossamer Pharma.
FM has served as a speaker and received honoraria from AbbVie, Biogen, Falk Pharma, Ferring, Hospira, Laboratorios Vitoria, Merck Sharp & Dohme, and Vifor.
PLL has been a speaker and/or advisory board member for AbbVie, Arena, Falk Pharma, Ferring, Genentech, Janssen, Kyowa Hakko Kirin Pharma, Mitsubishi Tanabe Pharma, MSD, Pfizer, Roche, Shire, Takeda, and Tillots; and has received unrestricted research grants from AbbVie, MSD, and Pfizer.
JOL has received grants for investigator led research from Takeda, Hospira / Pfizer, Abbvie, Gilead and has been a speaker and / or advisory board member for Allergan, Abbvie, Bristol Myers Squib, Celgene, Celltrion, Cornerstones US, Galapagos, Gilead, GSK, Lily, MSD UK, Shire, Ferring, Takeda, Pfizer, Janssen, Bristol Myers Squib,
TH has received research grants from AbbVie, Alfresa Pharma, Daiichi Sankyo, EA Pharma, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda. He has received lecture fees from AbbVie, EA Pharma, Janssen, Mitsubishi Tanabe Pharma, Pfizer, and Takeda.
BS has served as consultant for AbbVie, Boehringer, BMS, Celgene, Falk Pharma, Galapagos, Gilead, Janssen, Landos, Lilly, Pfizer, Prometheus, and Takeda, and received speaker’s fees from AbbVie, CED Service GmbH, BMS, Falk Pharma, Ferring, Galapagos, Janssen, Novartis, Pfizer, and Takeda.
ED, APL, AG, and CD, are employees of AbbVie, and may own AbbVie stock and/or stock options.
JDL has received personal fees, grants, and/or other support from AbbVie, Amgen, Arena Pharmaceuticals, Bridge Biotherapeutics, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen Pharmaceuticals, Johnson & Johnson Consumer Inc., Lilly, Merck, Nestle Health Science, Pfizer, Protagonist Therapeutics, Samsung Bioepis, Sanofi, Takeda, and UCB.
Funding: AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Morgan A Gingerich, PhD, of JB Ashtin, and funded by AbbVie.

Introduction

Corpus Atrophic Gastritis (CAG) is a precancerous inflammatory condition of the oxyntic mucosa. Up today, two types of CAG are distinguished: 1) autoimmune (corpus-restricted), defined for CAG sparing the antrum 2) Helicobacter pylori (Hp)-related (multifocal), which involves antrum too.
Antrum involvement/sparing is crucial for both CAG definition as autoimmune and gastric cancer risk level, which is increased in case of pan-atrophy/pan-metaplasia, according to OLGA and OLGIM scores. CAG natural history is still poorly known, especially regarding antrum evolution. In cases with previous antral involvement, possible antrum healing after cure of Hp infection was formerly described. So, given the importance of the criterium antrum-sparing, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.

Aims & Methods

Given the importance of the criterium antrum-spared, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.
We performed a retrospective study on 130 patients with CAG and antrum involvement according to updated Sydney System. Mean time of FU gastroscopy was 40.6(range 4-192) months. In 13 patients corpus atrophy was not confirmed at FU, so were excluded. At baseline, among the remaining 117 patients [mean age 63 (range 20-87) years; F 67.5%], 47 (40.2%) had antral non-atrophic and 70 (59.8%) had antral atrophic gastritis, metaplastic in 84.3%. Histologically diagnosed Hp infection was present in 27.3% of patients, all receiving eradication therapy, anti-parietal cells antibodies (APCA) were positive in 53.8%.

Results

At FU 29/117(24.8%) of patients with tout-court involved antrum showed a complete restitutio ad integrum of antral mucosa. In particular, on 70 cases with antral atrophy at baseline, atrophy regressed in 15 (21.4%). Hp infection at baseline was present in 38% of patients who reported complete antral healing at FU, cured in all but one. Both antral healing and atrophy regression were found to be similar in Hp-cured and not-cured/negatives (p>0.05). In 8 patients (6.8%) a worsening of antral histology at FU was reported: 5 developed antral atrophy, not present at baseline, and 3 antral atrophic patients developed intestinal metaplasia.

Conclusion

Nearly 25% of CAG patients with antral involvement showed complete antrum healing, with regression of baseline antral atrophy in 21.4%. Antral healing occurred also in patients without history of Hp infection and/or eradication. These data suggest that in CAG natural history, concomitant antral involvement may regress irrespective of Hp cure, implying cancer risk reduction and raising queries about histology as sole criteria diagnostic for autoimmune gastritis.

References

1. Lahner et al. Dig LIver Dis 2019
2. Sipponen P et al. Gastroenterology clinics of North America 2000
3. Annibale B Helicobacter 1997