Introduction

Endoscopic hand suturing (EHS), which enables intraluminal running suturing by using a through-the-scope type needle holder and an absorbable barbed suture, is expected to be applied to various situations. This technique is sometimes difficult to complete according to location, and if successful in suturing, dehiscence sometimes occurs afterward.

Aims & Methods

We aimed to investigate the technical difficulty and clinical courses of EHS for mucosal defect closure after gastric endoscopic submucosal dissection (ESD). We collected 74 lesions in 72 patients (15 prospectively-enrolled lesions for this analysis and 59 lesions from published data), including 49 patients (68%) having antithrombotic agents without cessation perioperatively. EHS was performed to close the mucosal defect immediately after gastric ESD, by suturing the mucosal layer continuously. A normal dose of antisecretory agents (proton-pump inhibitor or potassium-competitive acid blocker) was administered from the operative day to at least the postoperative day (POD) 28. A scheduled second-look endoscopy (SLE) was performed on POD 3 in 64 patients and on POD 7 in 8 patients, respectively. Technical success, closure maintenance on SLE, suturing speed (min/stitch), delayed bleeding, and severe adverse events (SAE) were evaluated. Furthermore, the difficulty and the clinical courses in EHS according to the location were assessed.

Results

EHS was performed on the upper (U)/middle (M)/lower (L) stomach in 10/32/32 lesions, and on the anterior wall (AW)/lesser curve (LC)/posterior wall (PW)/greater curve (GC) in 14/28/14/18 lesions, respectively. The mean diameter of the mucosal defects was 33 mm. The defect was completely closed in 73 lesions (99%), and the closure was maintained on SLE in 65 lesions (88%). The mean suturing duration and stitches were 41 min and 7 stitches, respectively, which indicated the suturing speed of 5.5 min/stitch. Delayed bleeding occurred in 2 lesions (3%), and no SAE was presented. The technical success rates were U/M/L: 90%/100%/100% (p = 0.039), and AW/LC/PW/GC: 100%/96%/100%/100% (p = 0.645), respectively. The closure maintenance rates were U/M/L: 80%/84%/94% (p = 0.371), whereas AW/LC/PW/GC: 100%/75%/93%/95% (p = 0.062). The suturing speed was not significantly different among the location.

Conclusion

This study showed that EHS was technically difficult on the upper third and the closure was inclined to dehisce on the lesser curvature side. For lesions on the upper stomach, it is desirable to perform EHS after obtaining sufficient experience. Furthermore, EHS should be provided more carefully and precisely for lesions on the lesser curvature to avoid postoperative dehiscence.

Introduction

GLIMMER (NCT02966834) was a Phase 2b study of the ileal bile acid transport (IBAT) inhibitor, linerixibat, for treatment of cholestatic pruritus in primary biliary cholangitis (PBC). The study included 147 patients: the largest trial in this population to date. GLIMMER had few restrictions on concomitant medications with the exceptions of other IBAT inhibitors, bile acid sequestrants and obeticholic acid; stable doses of other treatments were permitted.

Aims & Methods

In this analysis we explore the pruritus treatment history of patients entering GLIMMER. Investigators recorded details of prior and concomitant use of itch medications on the electronic case report form. For categorisation of prior and/or concomitant itch medication: prior only included patients who had tried and stopped at ≥1 pruritus medication before first study treatment and were not using anything else during treatment with linerixibat/placebo; concomitant only included patients who had used ≥1 pruritus medication in the past, which they continued to use during treatment; prior and concomitant included patients who had tried and stopped ≥1 pruritus medication prior to the study and, continued to use ≥1 pruritus medication during treatment with linerixibat/placebo. This post hoc analysis included all treatments prescribed for itch; guideline treatments were defined as bile acid sequestrants, naloxone, naltrexone, nalmefene, nalfurafine, sertraline, rifampicin or gabapentin. Pruritus severity was defined using worst itch numeric rating scale (NRS).

Results

At baseline, 24% of patients had mild (NRS <4), 52% moderate (NRS ≥4–<7) and 25% severe (NRS ≥7–10) pruritus. Mean age at baseline was 55.8 years but varied by itch severity, with mild patients being older (60.1 years) than those with moderate and severe pruritus (56.8 and 49.6 years, respectively). Median duration of pruritus at baseline was 6.3 years and those with mild pruritus tended to have a longer history than those with moderate or severe itch. Overall, a large proportion of patients were never previously treated: 37% (n = 55) had no prior/concomitant itch medications. Similar proportions of patients, 24% (n = 36) and 26% (n = 38), had received only prior itch medications or received prior and concomitant treatment for pruritus, respectively; 12% (n = 18) of patients were using only concomitant itch medications. Only 25% of patients were treated with cholestyramine, despite it being the guideline-recommended first-line therapy. Treatment history differed by baseline itch severity: 43% of mild patients had no prior or concomitant treatment versus 28% of severe patients. However, differences were less marked for concomitant pruritus therapy use: 43%, 36% and 39% of mild, moderate and severe patients, respectively, continued concomitant itch medicines in GLIMMER. The majority of concomitant itch treatments were non-guideline recommended, with only 39% receiving guideline treatments.

Conclusion

Consistent with the literature, increased itch severity is associated with younger age. Many patients do not receive treatment despite lengthy history of pruritus, while prior use of cholestyramine is limited despite its position in treatment guidelines.
Funding: GSK (201000).
Encore statement: This abstract was originally presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting on November 7, 2022, this encore is presented on behalf of the original authors with their permission.

Disclosure

HTS, AC, MMM, AJW and AR are employees of, and hold shares in GSK. SD is an employee of GSK.

Introduction

The best risk-stratification strategy to predict liver-related outcomes (LROs) in the population remains unclear. The Chronic Liver Disease (CLivD) risk score was recently developed and validated to predict LROs in the population. It could thus identify the at-risk population that warrants liver fibrosis screening with non-invasive tests such as FIB-4. The ClivD score is based on age, sex, waist-hip ratio, alcohol use, smoking, diabetes, and gamma-glutamyltransferase measurement.

Aims & Methods

We investigated the combined/sequential use of the ClivD score and FIB-4 for stratifying the risk for LROs in the UK Biobank population.
From the UK Biobank data, we identified 362,330 individuals with no baseline liver disease and data available to calculate the CLivD score and FIB-4. LROs were ascertained through linkage with electronic healthcare registries for hospitalizations, cancers, and deaths related to compensated or decompensated liver cirrhosis or hepatocellular carcinoma. Discrimination performance was assessed by 10-year competing-risk area-under-the-curve (AUC) values and absolute cumulative risks by the cumulative incidence functions considering death without liver disease as a competing-risk event.

Results

Mean age was 56.6 years (SD 8.1), 48% were men, mean BMI 27.2 kg/m2 (SD 4.6), 5% had diabetes, mean alcohol intake was 16.7 g/week (SD 16.6), and 10% were current smokers.
During a median follow-up of 12.6 years (IQR 12.0-13.4), there were 1285 incident LROs. Both the CLivD score and FIB-4 were significantly associated with LROs (P<0.001). The 10-year AUC-value of the CLivD score was 0.80 (95% CI 0.80-0.80) and of FIB-4, 0.75 (95% CI 0.75-0.75) for the prediction of LROs. The predictive performance of FIB-4 improved as a function of increasing CLivD scores: 10-year AUC values of FIB-4 were 0.61 in the minimal-risk CLivD subgroup as compared to 0.81 in the high-risk CLivD subgroup (Table). This effect modification of CLivD for FIB-4’s discrimination performance was also evident for absolute risks. Namely, within the minimal-risk CLivD subgroup, 10-year cumulative incidences of LROs ranged from 0.05% to 0.3% between low and high FIB-4 strata (Table). In contrast, within the high-risk CLivD subgroup, 10-year cumulative incidences of LROs ranged from 1.7% to 21.6% between low and high FIB-4 strata.

Conclusion

Defining the at-risk population by the CLivD score markedly improves the predictive performance of FIB-4. Thus, sequential use of the CLivD score and FIB-4 emerges as a simple way to stratify the population regarding the risk for LRO.

Introduction

Helicobacter pylori treatment´s effectiveness decreases as treatment eradication attempts fail.

Aims & Methods

To evaluate the use and effectiveness of empirical rescue therapies on third and subsequent lines in Europe.
Sub-study of the the European Registry on H. pylori Management (Hp-EuReg), an international, multicenter, prospective, non-interventionist registry starting in 2013 aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists (32 countries, 300 researchers). All infected adult patients were systematically registered at AEG-REDCap e-CRF until January 2023, all cases with three or more eradication attempts were extracted. Only the empirically prescribed therapies were analyzed. Data were subject to quality review.

Results

In total, 2,254 rescue treatments were included: 1,624, 424, 150 and 56 in third-, fourth-, fifth- and sixth-line treatments, respectively. Mean age was 52 years, 67% of patients were women and 5% were allergic to penicillin. Sixty-three different therapy regimens were used, being three-in-one single-capsule bismuth quadruple therapy the most commonly prescribed, as shown in the table. Overall effectiveness was 73% by modified intention-to-treat (mITT), and 74% by per-protocol (PP) analyses. Bismuth quadruple therapy as single-capsule provided the highest mITT cure rate (86%).One regimen achieved an optimal eradication rate (≥90%, by mITT): quadruple PPI-bismuth-tetracycline-metronidazole, only when high-dose PPIs and 14 days’ prescriptions were used. The use of doxycycline instead of tetracycline was associated with lower eradication rates in classical bismuth quadruple therapies (p<0.05).

Conclusion

Empirical rescue treatments in third and subsequent lines obtain, in general, suboptimal eradication rates in Europe; however, bismuth quadruple therapy as single-capsule obtained encouraging results. Only the optimised bismuth quadruple therapy with tetracycline-metronidazole achieved ≥90% effectiveness.

Disclosure

Olga P. Nyssen received research funding from Mayoly and Allergan.
Javier P. Gisbert served as speaker, consultant, and advisory member for or received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.