Introduction

The U.S. FDA has granted the PillCam™ SB3 @HOME program which allows patients to undergo SBCE at home. This program for SBCE remote use, however, is not cleared in the other countries, neither is a telehealth option of CCE worldwide.

Aims & Methods

We aimed to confirm compliance, safety, and acceptance of CCE and SBCE in the out-of-clinic setting in Japan. We enrolled 30 subjects who had not undergone CE (24 for CCE and 6 for SBCE) at 6 gastroenterological centers between June 2023 and February 2024. All examinees were provided with detailed instructions on how to interact with data-recorder automatic signaling, and for CCE examinees, low residue diet and a bowel preparation set including magnesium citrate, sodium picosulfate, PEG solution plus ascorbic acid, and castor oil. We prospectively collected data regarding baseline characteristics, compliance with procedures, CE results, acceptability with a subjectively categorized questionnaire survey, and adverse events using REDCap system (jRCTs042220163).

Results

Of 24 CCE examinees (male/female: 11/13, median age of 51 years, 23 for health check-up and 1 for positive fecal immunological test), 16 and 8 underwent CCE at home and at the workplace, respectively. Compliance rates of intake of low residue diet, recorder-capsule self-pairing, ingestion of CCE, intake of a bowel preparation set, return of equipment were all 100%. During the procedure, 12 examinees (50%) called the physician 18 times about when to finish (66.7%), how to take preparation (16.7%), and how to operate recorder (11.1%). Capsule excretion rate within examination time was 83% (20/24). In the 4 examinees who did not excrete the capsule, last images showed the rectum (n=1), transverse colon (n=1), ascending colon (n=1), and cecum (n=1). Median examination time between capsule ingestion and removal of sensor belt was 227 (80-1233) min; 208.5 (80-320) min and 697 (240-1233) min in examinees with or without capsule excretion, respectively (P=0.0118). The overall adequate endoscopic cleansing rate was 83%. Abnormalities were detected at 37.5% (9/24); colorectal polyps (25.0%), diverticula (8.3%), suspicious small bowel subepithelial tumor (4.2%). There was only one adverse event including intermittent abdominal pain. The proportions of examinees who reported “quite easy”, “fairly easy”, “moderate”, “fairly hard”, “quite hard”, and wished for CCE as the next examination were 17%, 25%, 25%, 29%, 4%, and 67%, respectively.
Of 6 SBCE examinees (male/female: 4/2, median age of 39 years, 2 for obscure GI bleeding and 1 for chronic diarrhea, 1 for ileitis, 1 for abdominal pain, 1 for health check-up), 4 and 2 underwent SBCE at home and at the workplace, respectively. Compliance rates of recorder-capsule self-pairing, ingestion of SBCE, return of equipment were all 100%. During the procedure, 3 examinees (50%) called the physician 4 times about when to finish (75.0%) and how to operate recorder (25.0%). Total enteroscopy rate within examination time was 100% (6/6). Median examination time between capsule ingestion and removal of sensor belt was 198 (158-372) min. The overall adequate endoscopic observation rate was 100%. Abnormalities were detected at 16.7% (1/6); duodenal polyp (n=1). There were no adverse events. The proportions of examinees who reported “quite easy”, “fairly easy”, and “moderate” were 33%, 33%, and 33%, respectively.

Conclusion

CCE and SBCE with all procedures in an out-of-clinic setting were feasible, safe, and comparable to those in a hospital setting, but remote consultations would be needed during the procedures.

Introduction

Individuals with alcohol use disorder (AUD) are at high risk of liver disease. Despite international clinical practice guidelines recommend screening for liver fibrosis in at risk populations, information regarding fibrosis prevalence, predictive factors and screening strategies in patients with AUD is scarce. Recently, a novel score (LiverRisk score) has been developed to predict liver fibrosis and liver-related outcomes in the general population.

Aims & Methods

We conducted a screening program for liver disease in subjects who attended the Addiction Unit of the Hospital Clínic of Barcelona between 2019 and 2022. Data regarding socio-economic status, medical history and alcohol consumption were recorded. Blood tests and transient elastography (TE) were performed in all patients. The main aim of the study was to analyze the prevalence of significant liver fibrosis in patients with AUD. The secondary objectives were to analyze the prevalence of advanced chronic liver disease in this population, identify the factors associated with the presence of significant liver fibrosis in patients with AUD and to evaluate the diagnostic accuracy of non-invasive liver fibrosis tests (Fibrosis-4 [FIB-4], NAFLD fibrosis score [NFS], Fatty Liver Index [FLI], AST to Platelet Ratio Index [APRI] and LiverRisk score) using TE as the Gold Standard. Significant liver fibrosis was defined as a liver stiffness (LS) value ≥ 8 kPa measured by TE. Advanced liver fibrosis was defined as a LS ≥ 15 kPa.

Results

Out of 334 total patients, 40 had significant liver fibrosis (prevalence of 12%). Out of the 40 patients with significant liver fibrosis, 19 (48%) had advanced chronic liver disease. Multiple factors were associated with the presence of significant fibrosis in univariate analysis; however, on multivariate analysis BMI (p=.04) and GGT levels (p=.001) were confirmed as the only independent predictors. Regarding non-invasive tests, the LiverRisk score was the test with the best diagnostic performance for detecting significant liver fibrosis, with an area under the receiver operating characteristic (AUROC) of 0’854. All other tests had similar diagnostic performance, with AUROC of 0’799 (NFS), 0’798 (FIB-4), 0’797 (FLI) and 0’784 (APRI).

Conclusion

The prevalence of significant liver fibrosis (TE > 8 kPa) in population with at-risk alcohol consumption is high. BMI and GGT are the main factors associated with the presence of liver fibrosis and could be useful for selecting patients with higher risk. The most accurate serological test to assess liver fibrosis in our cohort is the LiverRisk score. These results demonstrate the usefulness of a screening program for early detection of liver disease in patients with AUD and support the implementation of screening programs in this population.

References

1. Bataller R, Cabezas J, Aller R et al. Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH. Gastroenterology and Hepatology. 2019 Dec 1;42(10):657–76.
2. Caballería L, Pera G, Arteaga I et al. High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study. Clinical gastroenterology and hepatology. 2018 Jul 1;16(7):1138-1145.e5.
3. Berzigotti A, Tsochatzis E, Boursier J et al. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. Journal of Hepatology. 2021 Sep 1;75(3):659–89.
4. Pose E, Pera G, Torán P et al. Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population-based study. Liver International. 2021 [2021 Jun 16];00:1–9.
5. Ginès P, Castera L , Lammert F et al. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases. Hepatology. 2022 [2023 Oct 17];75:4.
6. Serra-Burriel M, Juanola A, Serra-Burriel F, et al. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study [published correction appears in Lancet. 2023 Sep 16;402(10406):964]. Lancet. 2023;402(10406):988-996. doi:10.1016/S0140-6736(23)01174-1

Disclosure

Pere Ginès has received research funding from Gilead & Grifols. He has consulted or attended advisory boards for Gilead, RallyBio, SeaBeLife, Merck, Sharp and Dohme (MSD), Ocelot Bio, Behring, Roche Diagnostics International and Boehringer Ingelheim, and received speaking fees from Pfizer. Ramon Bataller consults for GlaxoSmithKline, Novo Nordisk and Boehringer Ingelheim. He is on the speakers’ bureau for AbbVie and Gilead. Pol Bruguera is on the speakers’ bureau and received grants from Lundbeck. He received grants from Camurus and Pfizer. Maria T. Pons-Cabrera is employed by Lundbeck, Pfizer, and Esteve. Hugo López-Pelayo received grants from Lundbeck. The remaining authors declare that they have no conflicts of interest.

Introduction

Chromoendoscopy improves the visualization and differentiation of mucosal structures and enhances the polyp and adenoma detection rates. The dye-spray technique is a lengthy and laborious procedure. An oral formulation could serve as alternative, as demonstrated by Methylene Blue MMX. In contrast to methylene blue, patent blue V (E131) is an EFSA-approved food dye and practically free of side effects.

Aims & Methods

The aim of our case series was to encapsulate patent blue V in shellac food-grade microcapsules for oral intake and to evaluate the delayed release and mucosal staining as proof of principle.
Capsules filled with shellac microcapsules containing 100 mg patent blue V were produced by food technology for pH-dependent release in the ileum.
Between December 2016 and March 2022, 37 patients scheduled for a chromocolonoscopy volunteered to receive oral microcapsules for staining instead of the conventional dye-spraying procedure. 20 of the patients were additionally scheduled for a gastroscopy. Patients self-administered 4 capsules during the second half of the bowel preparation with KleanPrep (Norgine), at the latest 5 hours before chromocolonoscopy. Staining was rated by a score (0 points = not stained, 4 points = optimal even staining).

Results

The best staining quality was observed between the cecum and the sigmoid (ranges between 3.3 and 3.6 points). The terminal ileum (2.9 points) and rectum (3.1 points) were also stained acceptable. Absence of staining or overstaining were not reported. The mucosa in the upper gastrointestinal tract was not stained (0 points) in patients who underwent a gastroscopy on the same day. The polyp detection rate in our cohort was approximately 64%, the adenoma detection rate was 56%. The patent blue V capsules produced a good staining intensity, contrast of lesions, polyps and adenomas. The staining quality was rated equivalent to experience with dye-spraying chromocolonoscopy, with the advantage of clean equipment and a reduction of colonoscopy time.

Conclusion

Patent blue V microcapsules produced an even staining of the mucosal surface for chromocolonoscopy. Delayed-release patent blue V may be a superior and safe alternative to dye-spray techniques and Methylene Blue MMX with potential advantages in time of the procedure, sedation, cleaning, costs and skills. After this proof of concept, a randomized study with delayed-release patent blue V appears warranted.

References

1. Aziz M, Haghbin H, Sayeh W, et al. Comparison of Artificial Intelligence With Other Interventions to Improve Adenoma Detection Rate for Colonoscopy: A Network Meta-analysis. J Clin Gastroenterol 2022.
2. Repici A, Wallace MB, East JE, et al. Efficacy of Per-oral Methylene Blue Formulation for Screening Colonoscopy. Gastroenterology 2019;156:2198-2207.e1.
3. Fernando Aguilar, Riccardo Crebelli, Birgit Dusemund, Pierre Galtier, John Gilbert, David Gott, Ursula Gundert-Remy, Juergen König, Claude Lambré, Jean-Charles Leblanc, Alicja Mortensen, Pasquale Mosesso, Dominique Parent-Massin, Ivan Stankovic, Paul Tobb RAW and MW. Scientific Opinion on the re-evaluation of Patent Blue V (E 131) as a food additive. EFSA J 2013.
4. Theismann E-M, Keppler JK, Knipp J-R, et al. Adjustment of triple shellac coating for precise release of bioactive substances with different physico-chemical properties in the ileocolonic region. Int J Pharm 2019;564:472–484.

Disclosure

Introduction

The incidence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are notably higher in individuals diagnosed with type 2 diabetes mellitus (T2DM). However, studies evaluating the progression of MASLD in patients with T2DM and normal serum aminotransferase (ALT) levels are limited.

Aims & Methods

This 5-year prospective cohort study aimed to evaluate the progression of MASLD in T2DM patients with normal ALT. People with type 2 diabetes who had MASLD (defined by controlled attenuation parameter (CAP) >250 dB/min) and ALT levels that stayed normal (defined by ALT ≤40 IU/L for at least two occasions spanning at least six months) at Rajavithi Hospital, Bangkok, from November 2016 to 2017 were included. We excluded patients with viral hepatitis and alcohol consumption exceeding moderate levels. Transient elastography (TE) and CAP measurements were performed at baseline and ≥5 years of follow-up. The cutoffs to define significant and advanced fibrosis were TE >8 kPa and TE >12 kPa, respectively. All patients were instructed to reduce their weight and abstain from herbal remedies; medications for comorbidities were prescribed without limitations, subject to the physician's assessment. (most patients were under endocrinologist care.)

Results

The study included 84 patients, 57% of whom were female and had a mean age of 58.5 years. Of these, 62% were obese, with a mean BMI of 28.6 kg/m2. At baseline, the median TE was 6.92±3.35 kPa; 57 (68%) had no significant fibrosis, 22 (26%) had significant fibrosis, and 5 (6%) had advanced fibrosis, and after a 5-year follow-up, the median TE was 6.54±3.57 kPa; 69 (82%) had no significant fibrosis, 15 (18%) had significant fibrosis, and 2 (2%) had advanced fibrosis. During the follow-up, fibrosis decreased in 45 (54%), remained stable in 6 (7%), and increased in 33 (39%) patients, while a small proportion of patients experienced changes in the stages of fibrosis: 1.2% progressed from significant to advanced fibrosis; 17.4% regressed from advanced to significant fibrosis or transitioned from significant to no fibrosis; 12.8% remained stable with significant and advanced fibrosis; and the majority (66.3%) remained without significant fibrosis. A significant factor associated with fibrosis progression was alcohol consumption (p=0.013), while the use of angiotensin receptor blockers (p=0.042) was associated with fibrosis regression. Significant factors associated with steatosis progression included high baseline BMI (p=0.013), an increase in BMI ≥ 5% (p=0.04), high fasting plasma glucose, and LDL cholesterol levels, while a decrease in BMI ≥ 5% (p=0.002) the use of calcium channel blockers (p=0.038) and coffee consumption >3 cups per day (p=0.031) were associated with steatosis regression. ALT elevation during the follow-up occurred in a small proportion of patients, and it was not significantly associated with fibrosis or steatosis progression.

Conclusion

The majority of MASLD patients with T2DM and normal ALT maintained a relatively stable liver disease during 5 years of follow-up. Obesity, weight gain, alcohol consumption, and inadequate metabolic control were all associated with the progression of MASLD, whereas weight loss, coffee consumption, angiotensin receptor blockers, and calcium channel blockers were all associated with the improvement of MASLD.

Disclosure

I have nothing to disclose

Introduction

Metabolic dysfunction-associated steatohepatitis (MASH) is linked to increased risk of cardiovascular (CV) disease (CVD), but many aspects of CVD burden in patients with MASH remain unknown. Particularly, data on the clinical burden of CVD and specific CV events in patients with non-cirrhotic MASH vs those without non-cirrhotic MASH are limited.

Aims & Methods

The aim of this real-world study was to assess CVD burden in patients with and without non-cirrhotic MASH. Patients with MASH were identified using the International Classification of Diseases code for non-alcoholic steatohepatitis (K75.81) from October 2015–June 2022, using data from a federated network (TriNetX). The index date was defined as the date of first MASH diagnosis. Exclusion criteria were viral hepatitis, alcohol use disorder, chronic liver diseases other than MASH or metabolic dysfunction-associated steatotic liver disease, cirrhosis, decompensated MASH, hepatocellular carcinoma and human immunodeficiency virus. Patients with MASH were matched 1:1 to patients without MASH based on demographics (sex, age, year of start/end of insurance enrolment, and insurance scheme). Outcomes were CVD prevalence (assessed up to 1 year prior to index) and risk of CV events(s) during follow-up (index date to end of enrolment, death or study end) amongst patients with no history of respective CV event(s) at baseline. For CV risk, cumulative incidence was plotted using Aalen-Johansen curves after adjusting for competing risk of non-CV death. Incidence rate (IR) was calculated per 100 person-years (PY) and hazard ratios (HR) were calculated using Cox proportional hazard models (crude and adjusted for CV risk factors [age, sex, type 2 diabetes (T2D), chronic kidney disease (CKD), obesity, hyperlipidaemia and hypertension]).

Results

In total, 9,642 patients (4,821 with MASH; 4,821 without MASH) were included. In both groups, mean (standard deviation) age was 50.8 (13.2) years and 58.5% were women. Compared with those without MASH, more patients with MASH had hypertension (58% vs 31%), hyperlipidaemia (57% vs 30%), obesity (45% vs 17%), T2D (41% vs 14%) and CKD (6% vs 3%) at baseline. Prevalence of any CVD was higher in patients with MASH than without MASH (23% vs 12%), as was risk of any CV event (IR: 11.1 vs 4.5 per 100 PY; crude HR [95% confidence interval]: 2.72 [2.30, 3.22], p < 0.0001; adjusted HR: 2.27 [1.95, 2.66], p < 0.0001). Similar results were seen for individual CV events, namely ischaemic heart disease (IR: 5.3 vs 2.3), cerebrovascular disease (IR: 4.4 vs 2.1), atherosclerosis (IR: 3.9 vs 1.8), and heart failure (IR: 3.2 vs 1.5).

Conclusion

CVD prevalence at baseline and risk of CV events during follow-up were significantly higher in patients with non-cirrhotic MASH compared with matched controls without MASH in a real-world cohort. These data provide additional evidence of the association between MASH and CVD and complement a previous analysis of the unCoVer-MASH study.

Disclosure

EB has acted as a consultant for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Inventiva SA, Merck Sharp & Dohme (UK) limited, Novo Nordisk and Pfizer.
AM has no conflicts of interest.
KKM, ASC, KG, NK and ASP are employees of Novo Nordisk A/S and own employee shares/stocks.
KEC has acted as a consultant for Theratechnologies and Novo Nordisk, and has received grants from Bristol Myers Squibb and Novartis.

Introduction

Homocysteine (Hcy) levels are elevated in a variety of conditions, including cardiovascular diseases (CVD), diabetes, hyperinsulinemia, and metabolic-associated steatotic liver disease (MASLD). Although the relationship between MASLD and cardiovascular diseases (CVD) is epidemiologically well established (1), the pathogenetic process linking such conditions has not been completely clarified.

Aims & Methods

In this cross-sectional study, we analyzed Hcy levels in a population of 901 control and metabolic outpatients, considering the presence of MASLD and other dysmetabolic conditions, aiming to detect and deepen the putative role of Hcy in the relationship between liver steatosis and CVD. Hyperhomocysteinemia (HHcy) was defined for Hcy levels ≥15 μmol/l. Abdominal and carotid ultrasounds and comparison of Hcy levels were performed in all subjects.

Results

HHcy was identified in 140 subjects. Comparisons between subjects with Hcy<15 and Hcy>15 showed that the latter had significantly increased waist circumference (WC) (p=0.00001). HDL-c (p=0.00071) and 25-OH-Vitamin D (p=0.00002) levels were significantly lower, and triglycerides were significantly raised (p=0.04979) in subjects with HHcy compared to patients with Hcy<15.
We evaluated Hcy levels in subjects with and without such conditions, finding that Hcy did not differ between patients with and without carotid plaques (p=0.2182), but was different in presence of liver steatosis (p=0.00192) (Table 1).
Subjects with HHcy had a strong association with liver steatosis (chi-square p=0.00001), whereas we did not find the same association in presence of atherosclerotic plaques (chi-square p=0.08388). ORs analysis showed that subjects with HHcy subjects displayed an increased risk of fatty liver, with an OR of 2.1 (95% CI 1.3-3.2, p=0.00001), whilst the risk of being diagnosed with atherosclerotic plaques, though slightly increased (OR 1.2, 95% CI 0.8-1.7), was not significant (p=0.09938).
We calculated chi-square and ORs for HHcy association with increased BMI and each criterion of the IDF definition of MetS. In the overall population, regardless of the liver steatosis diagnosis, the cardiometabolic risk conditions significantly associated with HHcy were impaired fasting glycemia (FPG) (OR 2.1, 95% CI 1.4-3.1, p=0.00001), hypertriglyceridemia (OR 1.8, 95% CI 1.2-2.6, p=0.00028) and arterial hypertension (AH) (OR 1.7, 95% CI 1.4-3.1, p=0.00088).
In subjects with MASLD, the same analysis highlighted higher ORs, with hypertriglyceridemia showing the highest OR (3.3, 95% CI 2.6-3.8, p=0.00001), followed by AH (OR 2.6, 95% CI 1.9-2.9, p=0.00011), FPG (OR 2.5, 95% CI 2.1-2.8, p=0.00083) and WC (OR 2.4, 95% CI 1.6-2.8, p=0.00099), whilst the BMI criterion was not associated with HHcy.

Table 1. Comparison of homocysteine (Hcy) levels in patients with and without atherosclerotic plaque and liver steatosis.

Conclusion

Our data suggest an intriguing scenario where the reciprocal correlation between liver steatosis and HHcy may worsen underlying metabolic dysfunctions leading to CVD, and further exacerbate the key pathological features of MASLD. Addressing these interconnected risk factors could represent a crucial strategy for mitigating CVD burden in the increasingly prevalent population of patients with liver steatosis.

References

(1). Targher G, Byrne CD, Tilg H. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications. Gut 2024;73:691-702.

Introduction

Artificial intelligence may improve reading time and detection rate in small bowel capsule endoscopy (SBCE).

Aims & Methods

The study aimed to compare the effectiveness of artificial intelligence reading (AIR) with Navicam versus conventional reading (CR) with PillcamSB3.
A prospective pilot trial was conducted in a single center to assess the diagnostic performance of AIR compared to CR (non-inferiority study). Both endoscopic capsules were administered to the same patient in a randomized order at a 60-minute interval. AIR and CR were performed by two experienced independent endoscopists. Diagnostic yield (percentage of significant findings according to the clinical indication), diagnostic accuracy, and reading times of both explorations were assessed. All adverse events related to the study protocol were also registered.

Results

Twenty patients (median age 60 ± 10 years) were enrolled. Navicam and Pillcam showed similar completion rates (100% vs 95%, p=1) and diagnostic yield (80% vs 90%, p=0.5). Overall agreement was 90% (Cohen’s kappa 0.62). Compared to CR, in the per-patient analysis, AIR showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 88%, 100%, 100%, 60%, and 90%, respectively. In the per-lesion analysis, AIR showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 97%, 50%, 95%, 60%, and 93%, respectively. AIR showed significantly lower reading time than CR (3.2 vs 27.5 minutes, p<0.001). No adverse events or electromechanical interferences were observed during the study.

Conclusion

AIR with Navicam shows high agreement with CR with Pillcam. AIR demonstrates high diagnostic yield and accuracy, significantly reducing reading times.