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Introduction: Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF., Methods: In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation., Results: Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm 3 ), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression ( P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression ( P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores ( P < 0.05)., Discussion: Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF., (Copyright © 2024 by The American College of Gastroenterology.)

Small intestine, hitherto an obscure area for endoscopists before 2000, is now easily evaluated non-invasively using capsule endoscopy and invasively by device-assisted enteroscopies. Major advances in understanding the causes and management of small bowel diseases have been in obscure gastrointestinal (GI) bleed, currently re-named as small bowel bleed, after the discovery of capsule endoscopy. The current article is a narrative review of the technology of capsule endoscopy, its advantages and limitations, future perspective and Indian studies on its utility in patients with small bowel bleed. Till date, eight large series reporting 2319 patients with obscure GI bleed (1554 overt and 765 occult) undergoing capsule endoscopy have been reported from India. Overall yield of capsule endoscopy to detect lesions in these studies varied from 43.5% to 90%. The major causes detected in various studies for small bowel bleed include vascular malformation, portal hypertensive enteropathy, ulcer, stricture, tumor, polyps, etc. Hookworm can cause both occult as well as overt small bowel bleed as shown mainly from India. Capsule endoscopy has also been quite safe in patients with small bowel bleed as despite 0.6% to 15% retention of imaging capsule in Indian studies, development of clinically evident small bowel obstruction has rarely been reported. The major limitations of capsule endoscopy include lack of maneuvrability and therapeutic capability. Research is in progress to overcome some of the limitations of the current capsule endoscopy system. It is concluded that discovery of capsule endoscopy has brought a new paradigm in GI endoscopy and explored a hitherto unexplored area of GI tract, i.e. small bowel that continued to be a black box for the endoscopists., (© 2024. Indian Society of Gastroenterology.)

Background: Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum., Methods: In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled. Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140-350 g/week (or 20-50 g/day) for females and 210-420 g/week (or 30-60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated., Results: Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, -3.7 [IQR, -7 to -1.6]; MetALD, - 1.45 [IQR, -2.4 to 0.28]; and AALD, 0.71 [IQR, -1.3 to 4.8], respectively; P <0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (IQR, 0.72 to 0.84; cut-off <-3.5) and 0.80 (IQR, 0.74 to 0.86; cut-off >-1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUC diff =0.004; P =0.33)., Conclusion: AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT.

Background and Aim: Although rapid on-site cytological evaluation (ROSE) for endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA) may increase diagnostic yield, it is not widely available. Macroscopic on-site evaluation (MOSE) is an alternative modality although it is not standardized for EUS-guided fine-needle biopsy (FNB). We evaluated diagnostic performance of MOSE compared with conventional technique of EUS-TA using core biopsy needle., Methods: Consecutive patients undergoing EUS-FNA for solid lesions were randomized to MOSE or conventional arms. The primary and secondary outcome measures were diagnostic accuracy, diagnostic yield, sensitivity, specificity, positive and negative predictive values, and the number of passes, respectively. The optimum parameters for macroscopic visible core (MVC, i.e., length, number) by MOSE to achieve accurate diagnosis were evaluated., Results: Ninety-six patients (48 conventional and 48 MOSE) were enrolled. Mean lesion size was larger in MOSE arm (32.67 ± 7.22 vs 29.31 ± 6.98 mm, P = 0.023). Diagnostic accuracy (95.8% vs 91.6%), diagnostic yield (97.9% vs 95.8%), procedure duration, and adverse events of the two methods were similar. Median number of passes with MOSE was less (2 vs 3 P = 0.000). Area under the receiver operating characteristic curve showed that with MOSE, obtaining a total MVC length of 11.5 mm had 93.3% sensitivity, and 2.5 MVC cores (each 4 mm) had 86.7% sensitivity for malignancy diagnosis., Conclusions: EUS-FNB with MOSE, a simple reliable technique, can achieve a high and comparable diagnostic accuracy with lesser number of passes. Obtaining longer length and greater number of MVC increase the sensitivity to diagnose malignancy with MOSE., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aims: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring., Methods: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period., Results: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74., Conclusions: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Kuo: Equity holder in Apollo Endosurgery and patent applications for intellectual property related to cancer early detection. S. S. Mok: Consultant for Sovereign Laboratories, ConMed, and Medtronic-Covidien Corporation. M. A. Khashab: Advisory board member and consultant for Boston Scientific. E. J. M. van Geenen: Grants from Mylan and Olympus and personal fees outside the submitted work from MTW-Endoskopie. V. K. Singh: Grant support and personal fees outside the submitted work from AbbVie; advisory board participant for Ariel Precision Medicine, and Envara; grants from Orgenesis and Theraly; and advisory board participant for and stock options from Kyttaro. C. Tomasetti: Scientific advisory board member for PrognomiQ, Inc; royalty distributions from Exact Sciences (under a license agreement between Exact Sciences Corp and the Johns Hopkins University, C. Tomasetti and the university are entitled to royalty distributions); paid consultant for Bayer A; and patent applications for intellectual property related to cancer early detection (these arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies). V. S. Akshintala: Cofounder and chief medical officer for Origin Endoscopy and Solv Endotherapy and consultant for Dragonfly Endoscopy and Olympus. All other authors disclosed no financial relationships. C. Tomasetti received funding from the John Templeton Foundation., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: UCG has patents and applications for indigenous radio-opaque markers for a colon transit study, a double-lumen catheter for upper gut aspirate culture, a FODMAP fermentation chamber, BreathCalc, and a FODMAP meal challenge test. Although none of these patented products are currently on the market and the author has not yet received any royalty from them, he will start receiving royalty if they become commercially available. UCG also received research grants from Atmo Bioscience, Australia, through the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. UM and MKG declare no competing interests.

BACKGROUND AND OBJECTIVES: Persistent gastrointestinal (GI) symptoms and functional gastrointestinal disorders (FGIDs) are increasingly being recognized after Coronavirus disease-19 (COVID-19). Though quite a few studies addressed irritable bowel syndrome (IBS) following COVID-19, the disorders' prevalence varies greatly. We evaluated, (i) overall frequency of post-COVID-19 IBS, (ii) relative risk of development of IBS among COVID-19 patients compared to healthy controls using systematic review and meta-analysis techniques., Methods: Literature search was performed for studies on GI symptoms and FGIDs after COVID-19 using electronic databases (Medline, Scopus, Cochrane Central Register of Controlled Trials, Google Scholar and Web of Science) till April 28, 2023. We included studies reporting IBS after COVID-19 with any duration of follow-up and any number of subjects. Studies on pediatric population and those not providing relevant information were excluded. Relative risk of development of IBS using Rome criteria among COVID-19 patients compared to healthy controls was calculated. Analysis was done using MedCalc (Applied Math, Mariakerke, Belgium, version 7.2) and Comprehensive Meta-Analysis version 3.3.070 (Biostat Inc. Englewood, NJ 07631, USA)., Results: Of the available studies, 13 (four case-control) reporting on IBS after COVID-19 met inclusion criteria. Among 3950 COVID-19 patients and 991 controls, 7.2% of COVID-19 patients and 4.9% of healthy controls developed IBS. Of the four case-control studies reporting post-COVID-19 IBS, patients with COVID-19 were 2.65 (95% confidence interval [CI] 0.538 to 13.039) times more likely to have post-COVID-19 IBS as compared to healthy controls., Conclusions: Patients with COVID-19 are more likely to develop post-COVID-19 IBS than healthy controls. The heterogeneity of studies, different criteria used by various studies to diagnose post-COVID-19 IBS and some studies not meeting the six-month follow-up duration of the Rome criteria for diagnosing IBS are limitations of this systematic review., (© 2024. Indian Society of Gastroenterology.)

Background and Objectives: Hepatitis A virus (HAV)-related hepatitis is witnessing an epidemiological transition with increasing trends in adults. While uncomplicated hepatitis remains common, evidence suggests it to be a growing cause for acute liver failure (ALF). In between the two extremes exists severe acute liver injury (s-ALI) which has a propensity to transition to ALF. We aimed at describing the clinical profile of patients with HAV-related s-ALI and identifying potential predictors of progression to ALF., Methods: This was a single-center retrospective analysis of adult patients admitted with HAV-related s-ALI between April 2022 and December 2023. Demographic and laboratory parameters were compared between patients with only s-ALI and those with ALF. Predictors of progression from s-ALI to ALF were identified using logistic regression., Results: Forty-three patients satisfied criteria of s-ALI, of which 33 (76.7%) had only s-ALI, while 10 (23.3%) had ALF. Patients with s-ALI had lesser leukocytosis (6.3 ± 3 vs. 13.2 ± 4.8), less incidence of acute kidney injury (9.1% vs. 40%) and lower model for end-stage liver disease (MELD) (20 [18-24.5] vs. 31.5 [26-42]), arterial lactate (2.1 [1.3-3.1] vs. 6.3 [5.2-8.0]), arterial ammonia (94 [72-118] vs. 299 [188-573]), procalcitonin (0.5 [0.28-1.25] vs. 3.2 [1.2-6.1]) and ferritin (482 [213-1633] vs. 5186 [1341-11,053]) compared to HAV-ALF (p < 0.05 for all). Three patients (9.09%) with s-ALI progressed to ALF of whom one (3%) died. Baseline ammonia levels (unadjusted odds ratio [OR] 1.03 [1.01-1.06]) and leukocyte count (OR 1.00 [1.00-1.01]) tended to be associated with ALF progression, although none was significant after multi-variable adjustment. Ammonia levels had an area under receiver operating curve of 0.816 (0.64-0.93) (p = 0.009) (cut-off of 144 μmol/L). Additional comorbidities did not impact overall outcomes., Conclusion: HAV presents as s-ALI in young adults, with almost one in 10 progressing to ALF. Baseline ammonia may be an important predictor of progression even in s-ALI, but mandates larger well-designed studies., (© 2024. Indian Society of Gastroenterology.)

Video 1Demonstration of novel application of lumen-apposing metal stent for management of a malignant recto-sigmoid junction stricture with fistula., Competing Interests: The authors disclosed no financial relationships relevant to this publication., (© 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Introduction: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study., Methods: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP., Results: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume., Discussion: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings., (Copyright © 2023 by The American College of Gastroenterology.)

Competing Interests: The authors declare that they have no conflict of interest.

Objectives: Although countries like Japan and South Korea have implemented nationwide endoscopic screening programs, there is limited evidence on the effectiveness of endoscopy for diagnosing early gastric cancer (EGC) in developing countries such as India. In the present study, we aimed to determine the feasibility of endoscopic detection of EGC from India., Methods: The data was prospectively collected for all patients ≥40 years who underwent a diagnostic upper endoscopy from April to September 2021. A single endoscopist who performed the endoscopic procedures completed 1-month training in advanced endoscopy in Japan. Following the training, the endoscopist continued to engage in internet-based discussions regarding his cases encountered. Prior to this training, the endoscopist had not detected any EGC cases during his 12-year gastroenterology practice., Results: A total of 1033 patients were included in the study, with males accounting for 65.4% and a mean age 52 years. The average procedural time was 7.13 ± 4.8 min. A total of 25 patients (2.4%) were found to have GC, including 6 patients (0.6%) with EGC. Two patients had synchronous EGC lesions. All EGC patients were males, with an average age of 66 years. All EGCs were detected in the distal stomach in the presence of Helicobacter pylori infection and severe atrophic gastritis., Conclusion: Our findings showed that the endoscopic detection of EGC is feasible in India. Optimal training on endoscopic diagnosis of EGC can improve the detection of such lesion. Further studies are warranted to assess the optimization and implementation of an endoscopic screening program for EGC in India., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship., (© 2023. Indian Society of Gastroenterology.)

Background and Aims: Fluoroscopy-free endoscopic retrograde cholangiopancreatography for common bile duct stone (CBDS) clearance is usually offered only to pregnant patients. We initiated a multicenter, randomized controlled trial comparing clearance of non-complex CBDSs using fluoroscopy-free direct solitary cholangioscopy (DSC) to standard endoscopic retrograde cholangiography (ERC) to evaluate the wider applicability of the DSC-based approach. Here we report the initial results of stone clearance and safety in roll-in cases for the randomized controlled trial., Methods: Twelve expert endoscopists at tertiary care centers in four countries prospectively enrolled 47 patients with non-complex CBDSs for DSC-assisted CBDS removal in an index procedure including fluoroscopy-free cannulation. Successful CBDS clearance was first determined by DSC and subsequently validated by final occlusion cholangiogram as the ERC gold standard., Results: Fully fluoroscopy-free cannulation was successful in 42/47 (89.4%) patients. Brief fluoroscopy with minimal contrast injection was used in 4/47 (8.5%) patients during cannulation. Cannulation failed in 1/47 (2.1%) patients. Fluoroscopy-free complete stone clearance was reached in 38/46 (82.6%) cases. Residual stones were detected in the validation ERC occlusion cholangiogram in three cases. Overall serious adverse event rate was 2.1% (95% confidence interval 0.1-11.3): postprocedural pancreatitis in one patient., Conclusions: In patients with non-complex CBDS, the fluoroscopy-free technique is easily transferred to endoscopic retrograde cholangiopancreatography experts with acceptable rates of cannulation and stone clearance and few serious adverse events. (ClinicalTrials.gov number, NCT03421340)., Competing Interests: The authors disclose the following:Wiriyaporn Ridtitid: Research support from Boston Scientific CorporationRungsun Rerknimitr: Research support from Boston Scientific CorporationMohan Ramchandani: No disclosuresSundeep Lakhtakia: No disclosuresRaj J Shah: Consultant for Boston Scientific Corporation and OlympusJanak N Shah: Research support from Boston Scientific CorporationNirav Thosani: Consultant for Boston Scientific Corp, Pentax America, Ambu Inc; Speaker for Abbvie; Royalty from UpToDate; Creatorship Rights for ROSEAid IncMahesh K Goenka: no disclosuresGuido Costamagna: Research grants from Cook Medical and Boston Scientific, Advisory Board Grant from OlympusMihir S Wagh: Consultant for Boston Scientific, Olympus, Medtronic, Fujifilm, ConMed and Incyte; Research support from SterisVincenzo Perri: No financial relationships with a commercial entity producing health‐care‐related products and/or services relevant to this article.Joyce Peetermans: Full‐time employee of Boston Scientific CorporationPooja G Goswamy: Full‐time employee of Boston Scientific CorporationZoe Liu: Full‐time employee of Boston Scientific Corporation at the time of this studySrey Yin: Full‐time employee of Boston Scientific Corporation at the time of this studySubhas Banerjee: Boston Scientific: Consultant and research support; Ambys Medicines: consultant, (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objectives: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin., Methods: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP., Results: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002)., Conclusions: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The presence of anaemia has been linked to increased complications and a worse prognosis in cirrhosis. Spur cell anaemia (SCA) is a specific form of haemolytic anaemia reported in patients with advanced cirrhosis. The literature on the entity has not been systematically reviewed, despite the classical association and frequent association with worse outcomes. We undertook a narrative review of available literature on SCA which yielded only 4 were original studies, one case series and the rest of the literature as case reports and clinical images. SCA is usually defined by the presence of spur cell rate of ≥5%, although there remains a lack of consensus in the definition. SCA has been classically associated with alcohol-related cirrhosis but can be seen across the spectrum of cirrhosis and acute to chronic liver failure. Patients with SCA tend to have evidence of higher grades of liver dysfunction, abnormal lipid profiles, worse prognostic scores and a high mortality. Experimental therapies including corticosteroids, pentoxifylline, flunarizine and plasmapheresis has been tried with variable effect, but liver transplantation remains the management of choice. We propose a stepwise approach to diagnosis and re-enforce the need for further prospective research, especially in subgroups of advanced cirrhosis like acute to chronic liver failure., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF., Objective: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP., Methods: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex., Results: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m 2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05)., Conclusion: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Objectives: Psoas muscle parameters have been proposed as a simple and quick method for sarcopenia assessment. The aim of this study was to assess sarcopenia in cirrhotics by psoas muscle on computed tomography and its impact on mortality., Methods: One hundred and fifty patients (75 cirrhotics, 75 subjects) were assessed for psoas muscle on CT scan. Psoas muscle index (PMI) was calculated as 'total psoas muscle area/(height of subject) 2 '. Cut off values for sarcopenia diagnosis were derived from local subjects (n = 75) who did not have cirrhosis/other causes of sarcopenia., Results: Sarcopenia assessed by PMI was seen in 36% (n = 27) of the cirrhotics. Sarcopenia was significantly higher in patients having Child-Pugh C. Ascites, hepatic encephalopathy (HE) and gastro-intestinal bleed were seen in 48%, 18.7% and 24%, respectively. Sarcopenia was significantly associated with ascites and HE ( P  < 0.05). Out of the 75 cases, 53 cases completed the follow-up period of 1 year. Among the 20 cases who had sarcopenia, 35% (n = 7) succumbed to liver-related illness during 1 year follow-up, and out of the 33 cases without sarcopenia, only 6% (n = 2) died. The association of sarcopenia and 1 year mortality was statistically significant ( P  = 0.01)., Conclusions: The PMI, a simple method for sarcopenia assessment detected sarcopenia in 36% of cirrhotics. Patients with sarcopenia had a significantly higher 1 year mortality rate and appropriate prognostication of such patients is needed., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background and Aims: The quality of esophagogastroduodenoscopy (EGD) can have great impact on the detection of esophageal and gastric lesions, including malignancies. The aim of the study is to investigate the use of artificial intelligence (AI) during EGD by the  endoscopists-in-training so that a real-time feedback can be provided, ensuring compliance to a pre-decided protocol for examination., Methods: This is an observational pilot study. The videos of the EGD procedure performed between August 1, 2021, and September 30, 2021, were prospectively analyzed using AI system. The assessment of completeness of the procedure was done based on the visualizsation of pre-defined 29 locations. Endoscopists were divided into two categories - whether they are in the training period (category A) or have competed their endoscopy training (category B)., Results: A total of 277 procedures, which included 114 category-A and 163 category-B endoscopists, respectively, were included. Most commonly covered areas by the endoscopists were greater curvature of antrum (97.47%), second part of duodenum (96.75%), other parts of antrum such as the anterior, lesser curvature and the posterior aspect (96.75%, 94.95%, and 94.22%, respectively). Commonly missed or inadequately seen areas were vocal cords (99.28%), epiglottis (93.14%) and posterior, anterior, and lateral aspect of incisura (78.70%, 73.65%, and 73.53%, respectively). The good quality procedures were done predominantly by categoryB endoscopists (88.68% vs. 11.32%, p < 0.00001)., Conclusion: AI can play an important role in assessing the quality and completeness of EGD and can be a part of training of endoscopy in future., (© 2023. Indian Society of Gastroenterology.)

Background: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users., Methods: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas., Conclusions: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs., Trial Registration: NCT05252754, registered on February 14, 2022., Competing Interests: Declaration of competing interest Mouen Khashab reports advisory board member and consultant for Boston Scientific. Erwin J.M. van Geenen reports grants from Mylan and Olympus, personal fees from MTW-Endoskopie, outside the submitted work. Vikesh Singh reports personal fees from Abbvie, advisory board participant for Cook Medical, and grants from Orgenesis and Theraly. Venkata Akshintala is co-founder and chief medical officer of Origin Endoscopy Inc. All other authors declare no competing interests., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/aims: Fully covered self-expanding metal stents (FCSEMSs) are a relatively novel option for treating painful main pancreatic duct refractory strictures in patients with chronic pancreatitis. Herein, we aimed to assess the efficacy, feasibility, and safety of FCSEMSs in this patient group., Methods: This prospective single-center study included patients who underwent endoscopic retrograde pancreatography with FCSEMS placement. The primary endpoints were the technical and clinical success rates. A reduction in visual analog scale pain score of >50% compared with that before stent placement was defined as clinical success. Secondary endpoints were resolution of pancreatic strictures on fluoroscopy during endoscopic retrograde pancreatography and the development of stent-related adverse events., Results: Thirty-six patients were included in the analysis. The technical success rate was 100% (n=36) and the clinical success rate was 86.1% (n=31). There was a significant increase in stricture diameter from 1.7 mm to 3.5 mm (p<0.001) after stent removal. The mean visual analog scale pain score showed statistically significant improvement. At 19 months of follow-up, 55.6% of the patients were asymptomatic. Stent migration (16.7%), intolerable abdominal pain (8.3%), development of de novo strictures (8.3%), and mild pancreatitis (2.8%) were the most common adverse events., Conclusion: FCSEMS placement showed good technical and clinical success rates for achieving pain relief in patients with refractory main pancreatic duct strictures.

Competing Interests: The authors declare that they have no conflict of interest.

Background Most individuals with Covid-19 infection develop antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the dynamics of these antibodies is variable and not well-studied. We aimed to determine the titres of naturally acquired antibodies over a 12-week follow-up. Methods We recruited healthcare workers who had tested positive on a specific quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for SARS-CoV-2, and then tested for the presence of immunoglobulin G (IgG) antibody against the same virus at baseline and again at 6 and 12 weeks. The antibody titre was determined by a semi-quantitative assay based on signal/cut-off ratio. Healthcare workers with antibody positivity were divided into those with high titre (ratio ≥12) and low titre (<12). Their demographic details and risk factors were surveyed through a Google form and analysed in relation to the antibody titres at three time-points. Results Of the 286 healthcare workers, 10.48% had high antibody titres. Healthcare workers who had tested positive by qRT-PCR and those who had received the Bacille Calmette-Guérin (BCG) vaccination or other immune-boosters had a higher frequency of high antibody titres. While there was a significant decline in antibody titres at 6 and 12 weeks, 87.46% of individuals positive for IgG antibody persisted to have the antibody even at 12 weeks. Conclusion Healthcare workers who tested positive for SARS-CoV-2 on qRT-PCR had a high positivity for the specific antibody, which continued to express in them even at 12 weeks. Further follow-up is likely to enhance our understanding of antibody kinetics following SARS-CoV-2 infection.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: The authors declare that they have no conflict of interest.

Background & Aims: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups., Methods: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared., Results: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001)., Conclusion: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Acute variceal bleeding is the major cause of mortality in patients with cirrhosis. The standard medical and endoscopic treatment has reduced the mortality of variceal bleeding from 50% to 10-20%. The refractory variceal bleed is either because of failure to control the bleed or failure of secondary prophylaxis. The patients refractory to standard medical therapy need further interventions. The rescue therapies include balloon tamponade, self-expanding metal stents (SEMS) placement, shunt procedures, including transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), and endoscopic ultrasound (EUS) guided coiling. In cases where endoscopic variceal ligation (EVL) has failed and the variceal bleeding continues, temporary measures like balloon tamponade can be used to achieve hemostasis and as a bridge to definitive measures. SEMS being in use for refractory bleed is preferred over balloon tamponade due to the reduced complication rate. The shunting procedures are highly effective in reducing portal pressure and represent the gold standard for uncontrolled variceal bleeding. The surgical shunts, as well as nonshunt surgeries such as devascularization have become less popular with the increasing use of minimally invasive techniques like TIPS. TIPS have high success rates in controlling refractory variceal bleeding. The mortality rate is greater in high-risk patients undergoing salvage TIPS, and hence, pre-emptive TIPS should be considered in these patients. BRTO is an interventional radiologic procedure used in the management of bleeding gastric and ectopic varices. The availability of gastrorenal or splenorenal shunts is required for the BRTO procedure, which helps to reach and obliterate the cardiofundal varices through the femoral or jugular vein approach. The EUS guided coiling and glue injection have shown promising results, and further randomized controlled trials are required to establish their efficacy for refractory variceal bleeding., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Background/objectives: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry., Methods: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission., Results: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent., Conclusion: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP., (Copyright © 2021. Published by Elsevier B.V.)

Video 1Video demonstrating the EUS-rendezvous technique for biliary access and removal of a long biliary ascariasis., (© 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis., Methods: We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606., Findings: We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4-13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00-0·40), intramuscular diclofenac 75 mg (0·24, 0·09-0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16-0·55), intravenous high-volume Ringer's lactate (0·31, 0·12-0·78), 5-7 Fr pancreatic stents (0·35, 0·26-0·48), rectal diclofenac 100 mg (0·36, 0·25-0·52), 3 Fr pancreatic stents (0·47, 0·26-0·87), and rectal indometacin 100 mg (0·60, 0·50-0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5-7 Fr pancreatic stents (0·59, 0·41-0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26-0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00-0·66), and rectal diclofenac 100 mg (0·59, 0·40-0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons., Interpretation: This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis., Funding: None., Competing Interests: Declaration of interests JPHD reports grants from Gilead, outside the submitted work. BJE reports personal fees from Takeda Pharmaceuticals, outside the submitted work. MK is an advisory board member and consultant for Boston Scientific, outside the submitted work. ANK is an equity holder for Apollo Endosurgery, outside the submitted work. EJMvG reports grants from Mylan and Olympus and personal fees from MTW-Endoskopie, outside the submitted work. VKS reports personal fees from AbbVie, grants from Orgenesis and Theraly, and is an advisory board participant for Cook Medical, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF) has emerged to be a promising tool in quantification of liver fat. Aim of this study was to quantify liver fat using MRI-PDFF in patients with suspected non-alcoholic fatty liver disease (NAFLD) and to correlate it with the presence of metabolic syndrome (MetS), ultrasonography (USG) and liver function test (LFT)., Methods: We included 111 consecutive patients who were suspected to have NAFLD on the basis of clinical, laboratory or USG findings. A 3 Tesla Phillips MRI machine was used with a software named "mDixon Quant" for quantification of the liver fat., Results: MRI-PDFF revealed hepatic steatosis grading as Grade 0 in 31 patients (28%), Grade I in 40 (36%), Grade II in 19 (17.1%) and Grade III in 21 patients (18.9%). MetS patients had higher proportion of advanced steatosis (Grades II and III) as compared to those without MetS ( P  < 0.001). ALT (alanine transaminase) was found to be significantly elevated (>1.5 times) in the patients with advanced steatosis as compared to patients with Grades I and 0 fatty liver on MRI-PDFF ( P  < 0.001). The Kappa measure of agreement between USG and MRI-PDFF was found to be 0.2, which suggests a low level of agreement between the two tests., Conclusion: MetS patients have higher proportion of advanced steatosis (Grades II and III) at MRI-PDFF as compared to those without MetS. Patients with advanced steatosis at MRI-PDFF had higher proportion of abnormal LFTs as compared to those with Grades 0 and I hepatic steatosis. There was a dis-correlation between MRI-PDFF and USG in the evaluation of NAFLD., (© 2020 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)