Introduction

Acute variceal bleeding (AVB) is a common and life-threatening complication of cirrhosis and portal hypertension. Despite advances in therapeutic strategies, the 6-week mortality rate remains high, ranging from 10% to 20%. Current clinical guidelines recommend standard treatment for cirrhotic patients with AVB, including vasoactive agents, prophylactic antibiotics, and endoscopic intervention. However, real-world clinical practices are often influenced by physician awareness, institutional resources, and patient preferences. In late 2019, West China Hospital of Sichuan University established a multidisciplinary rapid-response pathway for the emergency management of high-risk upper gastrointestinal bleeding (UGIB). This initiative aimed to improve the treatment protocol, integrate endoscopic and interventional resources, and finally improve the outcomes.

Aims & Methods

The present study evaluates the impact of this rapid-response pathway on clinical outcomes in cirrhotic patients with AVB. This retrospective study included consecutive patients admitted for acute UGIB to West China Hospital between January 2016 and November 2022. Inclusion criteria were: (1) cirrhosis; and (2) presentation with hematemesis and/or melena within five days before admission. Exclusion criteria included: (1) non-variceal bleeding or an unconfirmed bleeding source on endoscopy; and (2) less than six weeks of follow-up. Patients were categorized into two groups based on the timing of rapid-response pathway implementation: Group A (2016–2019, pre-implementation) and Group B (2020–2022, post-implementation). Primary outcomes were 6-week mortality and 5-day treatment failure. Propensity score matching (PSM) was applied to adjust for baseline confounders: a 1:1 PSM was used to compare Group A and B.

Results

A total of 1,529 cirrhotic patients with AVB were included. Following 1:1 PSM, Groups A and B comprised 654 patients each. The most common etiology of cirrhosis is chronic hepatitis B virus infection. No significant intergroup differences were observed in Child-Pugh score, MELD score, MELD-Na score, prevalence of PVT, HCC, infection, ascites, or hepatic encephalopathy (all P > 0.05). Group B had a higher rate of prophylactic antibiotics, early endoscopic or interventional treatment use, and less balloon tamponade and intubation. Group B demonstrated significantly lower 6-week mortality compared to Group A [52 (8.0%) vs. 88 (13.5%), P = 0.001]. Multivariate Cox regression identified Child-Pugh score (HR = 1.203), MELD-Na score (HR = 1.040), PVT (HR = 1.733), HCC (HR = 2.398), and 5-day treatment failure (HR = 4.385) as independent risk factors for 6-week mortality. Similarly, Group B exhibited a significantly reduced 5-day treatment failure rate [64 (9.8%) vs. 137 (20.9%), P < 0.001]. While no significant differences in overall 6-week mortality or 5-day treatment failure were observed between the PVT and non-PVT groups, patients with coPVT had significantly higher 6-week mortality compared to non-PVT patients (HR = 4.81).

Conclusion

The implementation of a multidisciplinary rapid-response pathway significantly improved early intervention, endoscopy utilization, and TIPS procedures in cirrhotic patients with AVB. These changes were associated with marked reductions in both 6-week mortality and 5-day treatment failure. Key independent predictors of 6-week mortality included Child-Pugh score, MELD-Na score, HCC, PVT, and 5-day treatment failure.

Introduction

Patients with acute-on-chronic liver failure (ACLF) have traditionally been considered with a tendecy for bleeding however, they frequently display a paradoxical prothrombotic state. ACLF is characterized systemic inflammation and an increased risk of both bleeding and thrombosis. Bleeding arises from decreased pro-coagulation factors and platelet sequestration due to portal hypertension, while thrombosis is exacerbated by endothelial dysfunction and elevated heparinoids, thrombomodulin, or von Willebrand factor.

Aims & Methods

The aim of this study was to evaluate platelet aggregation pattern in patients with ACLF compared to acute decompensated (AD) liver cirrhosis.
The study took place in between the 1^st of July 2024- 31^st of January 2025 and we prospectively included cirrhotic patients, divided in two groups: ACLF group and AD group. The exclusion criteria were people with compensated liver cirrhosis, antiaggregant or anticoagulant treatment and patients with hepatocellular carcinoma or other malignancies. We investigated platelet aggregability in whole blood, by using multiplate aggregometry. For analysis, platelet aggregometry was performed induced by: adenosine diphosphate (ADP), arachidonic acid (ASPI), prostaglandin E2 (PGE2) and thrombin receptor-activated peptide (TRAP-6) as agonist were determined. TRAP‑6 is a peptide that stimulates protease-activated receptor 1 (PAR1) on platelet membrane.

Results

In this study we included 52 patients – 25 patients with ACLF and 27 patients with AD. There were no differences regarding demographic parameters and liver disease etiology between the two study groups. Compared to AD group, patients with ACLF showed an enhanced maximal platelet aggregation with TRAP-6 (AUC 85±12 U vs 45±10 U, p<0.0001). In contrast, we did not detect any differences in platelet aggregation between the two groups after ADP, ASPI or PGE2 activations. We observe that PAR-1 stimulation induces the highest aggregation curve and area under the curve in patients with ACLF and AD, but ACLF patients show the strongest response, highlighting that the degree of liver decompensation influences aggregation results. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

Conclusion

Our results indirectly indicate that platelet reactivity is higher in patients with ACLF likely due to enhanced PAR-1 receptor activity. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

References

1. EASL Clinical Practice Guidelines on acute on liver failure; J. Hepatol. 2023
2. Napolitano et al. European Journal of Internal Medicine 2017
3. Tripodi et al. Hepatology 2006
4. Lisman et al. Hepatology 2006
5. Nassar et al. BIOMEDICINES 2023
6. Rogalski et al. Scandinavian Journal of Gastroenterology 2019
7. Zanetto et al. Liver International 2022
8. Vecerzan et al. Cureus 2024
​

Introduction

Inflammatory bowel disease is a chronic, relapsing condition influenced by genetic, microbial, and environmental factors. This study evaluated the therapeutic potential of multi-strain probiotics in mitigating the severity of experimentally induced colitis in rats, focusing on clinical outcomes, histopathological changes, inflammatory markers, and microbiota changes.

Aims & Methods

Thirty six-week-old male Sprague-Dawley rats were randomly assigned to three groups: Control, Acute Colitis (AC), and Probiotic Treatment (RP; receiving Lactobacillus rhamnosus and Lactobacillus paracasei). Probiotics were administered orally once daily, beginning three days prior to colitis induction with rectal DNBS and continued for seven days post-induction. On day eight, colon tissues and blood samples were collected for histological and biochemical analysis, and fecal samples were analyzed to assess gut microbiota composition.

Results

The AC group showed significantly elevated TNF-α levels compared to the Control and RP groups (p < 0.001), while probiotic treatment significantly reduced TNF-α levels compared to the AC group (p = 0.002, p < 0.001, respectively). Although the RP group demonstrated increased IL-10 levels and decreased MDA levels, these changes were not statistically significant. Histopathological analysis revealed a lower median Ameho’s score in the RP group compared to the AC group, though without statistical significance.

Microbiota analysis showed no significant differences in alpha diversity across groups. However, beta diversity significantly differed in the AC group compared to Control, and after probiotic treatment, the RP group’s beta diversity showed a partial shift toward the Control group. Distinct microbial species characterized each group: Akkermansia spp. and Parasutterella spp. were predominant in distinguishing the Control group from others; Romboutsia spp. and Turicibacter spp. differentiated the AC group; and Roseburia spp. and Anaerotruncus spp. were the key species distinguishing the RP group from the others.

Conclusion

Multi-strain probiotics reduced TNF-α levels and modulated gut microbiota composition in DNBS-induced colitis. Although changes in IL-10, MDA, and histopathology were not statistically significant, trends favored the probiotic group. Microbial analysis revealed distinct species profiles across groups, with partial restoration of beta diversity and enrichment of beneficial taxa like Roseburia spp. in the probiotic group. These findings support the potential of probiotics as a therapeutic adjunct in IBD, highlighting the need for further studies to confirm efficacy and explore underlying mechanisms.

Introduction

The STRIDE-II consensus on the management of Crohn’s disease (CD) highlights the importance of achieving multiple treatment targets, including clinical remission, normalisation of the inflammatory biomarkers high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP), and quality of life (QoL) improvements.¹ In this post hoc analysis of the SEQUENCE open-label extension (OLE), we assessed inflammatory biomarker reductions and improvements in clinical and QoL outcomes (alone or in combination) in patients (pts) with moderately to severely active CD treated with risankizumab (RZB), an interleukin-23 p19 inhibitor.

Aims & Methods

In Part 2 of SEQUENCE (NCT04524611), pts randomised to the RZB arm during Part 1 and who completed the week (wk) 48 visit were eligible to continue receiving open-label 360mg subcutaneous RZB maintenance dose every 8 wks.² This analysis included all patients who completed wk100 of RZB treatment or who discontinued treatment prior to wk100 in Part 2 (cutoff date: July 11, 2024). Pts with elevated hs-CRP (> 5 mg/L) or FCP (> 250 mg/kg) at induction baseline were assessed for achievement of normalised hs-CRP or FCP alone or in combination with clinical remission per CD activity index (CDAI) or per stool frequency/abdominal pain score (SF/APS), or with inflammatory bowel disease questionnaire (IBDQ) remission (endpoints defined in Table footnote) at wks 52 (OLE baseline), 76, and 100. Data were assessed for all intent-to-treat pts using as observed (AO) regardless of rescue therapy and nonresponder imputation (NRI). Safety was previously reported and not assessed in this post hoc analysis.³

Results

Of the 224 pts who entered SEQUENCE Part 2, 184 pts had elevated hs-CRP or FCP levels at induction baseline and were included in this analysis. The majority of these pts achieved normalisation of hs-CRP or FCP (per AO data) at wk52 (77.7%) and continued to show improvement at wks 76 and 100 (83.9% and 86.6%, respectively) (Table). Most of these pts also achieved both normalised hs-CRP or FCP and clinical remission simultaneously at wks 52, 76, and 100 per CDAI (AO data: 60.9%, 66.2%, and 71.0%, respectively) and per SF/APS (AO data: 55.2%, 60.2%, and 62.9%, respectively). The proportion of pts who achieved normalisation of hs-CRP or FCP and IBDQ remission increased from wk52 through wk100 (AO data; wk52: 50.0%, wk76: 54.9%, wk100: 57.1%). NRI data for all endpoints are summarized in the Table.

Conclusion

In this post hoc analysis, pts with moderately to severely active CD demonstrated inflammatory biomarker normalisation with RZB treatment and continued improvement of inflammation up to wk100 in the SEQUENCE OLE. Notably, most pts simultaneously achieved normalisation of inflammatory biomarkers plus clinical or QoL outcomes through wk100 of RZB treatment.

References

1. Turner D, et al. Gastroenterology. 2021;160:1570–83.
2. Peyrin-Biroulet L, et al. N Engl J Med. 2024;391:213–23.
3. L Peyrin-Biroulet, et al. Journal of Crohn's and Colitis. 2025;19(Supplement_1):i1405–07.

Disclosure

Benjamin L. Cohen has received advisory board and consultancy fees from AbbVie, ALPCO, Celgene-Bristol Myers Squibb, Johnson & Johnson Innovative Medicine, Lilly, Pfizer, Sublimity Therapeutics, Takeda, TARGET RWE; DSMB: Emmes Biopharma Services LLC; speakers’ fees from AbbVie and Takeda.
Corey Siegel has served as a consultant for AbbVie, BMS, Boomerang, Buhlmann, Celltrion, Johnson & Johnson, Lilly, Napo Pharmaceuticals, Path Healthcare, Pfizer, Prometheus Biosciences & Labs, Sanofi, Takeda, and Trellus Health; received grants from AbbVie, Johson & Johnson, Pfizer, and Takeda; and is co-founder of MiTest Health, LLC, technology “System and Method of Communicating Predicted Medical Outcomes” licensed to Takeda; equity interest in Path Healthcare and Trellus Health
Alessandro Armuzzi has received consulting/advisory board fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; speaker’s fees from AbbVie, Alfa Sigma, Amgen, Arena, Biogen, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Teva Pharmaceuticals; and research support from MSD, Takeda, Pfizer, and Biogen.
Fernando Aponte, Toni Anschutz, Andrew Garrison, Namita Joshi, and Javier Zambrano are full-time employees of AbbVie and may own AbbVie stock or stock options.
Laurent Peyrin-Biroulet has received personal fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio.

Funding
AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. Medical writing support was provided by Mahesh Chemudupati, PhD of AbbVie. Editorial support was provided by Amy Kuang, PhD of AbbVie.

Introduction

Despite the availability of clinical guidelines, a wide range of alternative Helicobacter pylori (H. pylori) eradication regimens continue to be used in routine clinical practice. Data on the frequency and effectiveness of these less frequently prescribed regimens remain limited.

Aims & Methods

Aim: To evaluate the prescription patterns and effectiveness of less frequently prescribed eradication regimens within the European Registry on Helicobacter pylori Management (Hp-EuReg).
Methods: International, multicentre, prospective, non-interventional registry on the management of H. pylori infection, ongoing since 2013. For this analysis, treatment regimens prescribed in fewer than 5% of all cases were classified as 'less frequently prescribed'. Additionally, therapies not previously categorized in the registry database were also included. Treatment effectiveness was assessed using modified intention-to-treat (mITT) and per-protocol (PP) analyses.

Results

Overall, 260 less frequently prescribed regimens were identified, representing 5.5% of all recorded prescriptions (82,510). A total of 2,853 (63%) of these regimens were used as first-line therapy. Among these less frequently prescribed regimens, the most frequently used first-line treatments encompassed bismuth-containing quadruple therapy with PPI–clarithromycin–metronidazole–bismuth (20%), followed by non-bismuth hybrid quadruple therapy with clarithromycin–amoxicillin–metronidazole (9.5%), and dual therapy with PPI–amoxicillin (8.6%). In second-line, the most common regimens were triple therapies, such as the PPI–amoxicillin–moxifloxacin (16%), PPI–clarithromycin–levofloxacin (11%), and PPI–metronidazole–levofloxacin (9.5%). In third-line, the most frequently used regimes were bismuth-based quadruple regimens including PPI–metronidazole–doxycycline–bismuth (27%), followed by triple therapies with PPI–clarithromycin–levofloxacin (6.8%) and PPI–amoxicillin–moxifloxacin (5.6%). In the fourth-line, the most frequent prescriptions were: bismuth-based quadruple therapies including PPI–amoxicillin–rifabutin–bismuth (30%) and PPI–metronidazole–doxycycline–bismuth (11%). Finally, the fifth treatment-line accounted for some less common treatments, such as the dual therapy with PPI–amoxicillin (19%) and the triple therapy with PPI–amoxicillin–bismuth (18%). Effectiveness and frequency of use in first-, second- and third-line of treatment are described in Table 1. Antibiotic-free regimens such as the combination of a PPI with a probiotic —generally Lactobacillus bulgaricus or Lactobacillus reuteri—were prescribed as alternative therapeutic approaches in 104 cases (2.3%), achieving 74% mITT and 76% PP overall effectiveness.
​

Conclusion

Among the various less frequently used H. pylori eradication regimens, only a few (such as the PPI-clarithromycin-metronidazole-bismuth regimen and the hybrid regimen including clarithromycin–amoxicillin–metronidazole) achieved first-line eradication rates above 90%. In subsequent treatment lines, effectiveness was highly variable and often suboptimal. These findings highlight the importance of evidence-based treatment selection to optimize treatment outcomes.

Disclosure

Conflict of interest statement
Olga P. Nyssen has served as a speaker or has received research funding from Allergan, Mayoly Spindler, Richen, Biocodex and Juvisé.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé, Biocodex.
The remaining authors declare no conflicts of interest.