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Abstract Background: Helicobacter pylori eradication is the mainstay in the treatment of H. pylori-associated peptic ulcer disease. Metronidazole is an important component in most eradication regimens. However, the presence of metronidazole-resistant H. pylori adversely affects the efficacy of such regimens. We aimed to study the prevalence of metronidazole resistance in our population, and the factors associated with its presence. Methods and Results: From September 1993 to September 1996, 459 H. pylori isolates were collected and analysed. The overall resistance rate was 62.7%. The rate was significantly higher among women compared with men (P < 0.05). When the results were analysed according to each year, there was a significant increase in the resistance rate from 50.5% in the first year to 72.7% in the third year (P = 0.0039). Conclusions: There was a significant rise in the prevalence of metronidazole resistance over a 3-year period. The presence of metronidazole resistance adversely affects the eradication rates of nitroimidazole-based regimens. Hence, in a population with a high prevalence of metronidazole resistance, the use of non-nitroimidazole-based therapy may be more efficacious. This information on resistance rates is important for the empirical choice of antibiotic against H. pylori in a population. [ABSTRACT FROM AUTHOR]

Background: Recent developments in artificial intelligence (AI) systems have enabled advancements in endoscopy. Deep learning systems, using convolutional neural networks, have allowed for real-time AI-aided detection of polyps with higher sensitivity than the average endoscopist. However, not all endoscopists welcome the advent of AI systems., Methods: We conducted a survey on the knowledge of AI, perceptions of AI in medicine, and behaviours regarding use of AI-aided colonoscopy, in a single centre 2 months after the implementation of Medtronic's GI Genius in colonoscopy. We obtained a response rate of 66.7% (16/24) amongst consultant-grade endoscopists. Fisher's exact test was used to calculate the significance of correlations., Results: Knowledge of AI varied widely amongst endoscopists. Most endoscopists were optimistic about AI's capabilities in performing objective administrative and clinical tasks, but reserved about AI providing personalised, empathetic care. 68.8% (n = 11) of endoscopists agreed or strongly agreed that GI Genius should be used as an adjunct in colonoscopy. In analysing the 31.3% (n = 5) of endoscopists who disagreed or were ambivalent about its use, there was no significant correlation with their knowledge or perceptions of AI, but a significant number did not enjoy using the programme (p-value = 0.0128) and did not think it improved the quality of colonoscopy (p-value = 0.033)., Conclusions: Acceptance of AI-aided colonoscopy systems is more related to the endoscopist's experience with using the programme, rather than general knowledge or perceptions towards AI. Uptake of such systems will rely greatly on how the device is delivered to the end user., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The development of deep learning systems in artificial intelligence (AI) has enabled advances in endoscopy, and AI-aided colonoscopy has recently been ushered into clinical practice as a clinical decision-support tool. This has enabled real-time AI-aided detection of polyps with a higher sensitivity than the average endoscopist, and evidence to support its use has been promising thus far. This review article provides a summary of currently published data relating to AI-aided colonoscopy, discusses current clinical applications, and introduces ongoing research directions. We also explore endoscopists' perceptions and attitudes toward the use of this technology, and discuss factors influencing its uptake in clinical practice.

Background: Colonoscopies have long been the gold standard for detection of pre-malignant neoplastic lesions of the colon. Our previous study tried real-time artificial intelligence (AI)-aided colonoscopy over a three-month period and found significant improvements in collective and individual endoscopist's adenoma detection rates compared to baseline. As an expansion, this study evaluates the 1-year performance of AI-aided colonoscopy in the same institution., Methods: A prospective cohort study was conducted in a single institution in Singapore. The AI software used was GI Genius™ Intelligent Endoscopy Module, US-DG-2000309 © 2021 Medtronic. Between July 2021 and June 2022, polypectomy rates in non-AI-aided colonoscopies and AI-aided colonoscopies were calculated and compared. Some of the AI-aided colonoscopies were recorded and video reviewed. A "hit" was defined as a sustained detection of an area by the AI. If a polypectomy was performed for a "hit," its histology was reviewed. Additional calculations for polyp detection rate (PDR), adenoma detection rate (ADR), and adenoma detection per colonoscopy (ADPC) were performed. Cost analysis was performed to determine cost effectiveness of subscription to the AI program., Results: 2433 AI-aided colonoscopies were performed between July 2021 and June 2022 and compared against 1770 non-AI-aided colonoscopies. AI-aided colonoscopies yielded significantly higher rates of polypectomies (33.6%) as compared with non-AI-aided colonoscopies (28.4%) (p < 0.001). Among the AI-aided colonoscopies, 1050 were reviewed and a final 843 were included for additional analysis. The polypectomy to "hit" ratio was 57.4%, PDR = 45.6%, ADR = 32.4%, and ADPC = 2.08. Histological review showed that 25 polyps (3.13%) were sessile-serrated adenomas. Cost analysis found that the increased polypectomy rates in AI-aided colonoscopes led to an increase in revenue, which covered the subscription cost with an excess of USD 20,000., Conclusion: AI-aided colonoscopy is a cost effective means of improving colonoscopy quality and may help advance colorectal cancer screening in Singapore., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Colonoscopy is a mainstay to detect premalignant neoplastic lesions in the colon. Real-time Artificial Intelligence (AI)-aided colonoscopy purportedly improves the polyp detection rate, especially for small flat lesions. The aim of this study is to evaluate the performance of real-time AI-aided colonoscopy in the detection of colonic polyps., Methods: A prospective single institution cohort study was conducted in Singapore. All real-time AI-aided colonoscopies, regardless of indication, performed by specialist-grade endoscopists were anonymously recorded from July to September 2021 and reviewed by 2 independent authors (FHK, JL). Sustained detection of an area by the program was regarded as a "hit". Histology for the polypectomies were reviewed to determine adenoma detection rate (ADR). Individual endoscopist's performance with AI were compared against their baseline performance without AI endoscopy., Results: A total of 24 (82.8%) endoscopists participated with 18 (62.1%) performing ≥ 5 AI-aided colonoscopies. Of the 18, 72.2% (n = 13) were general surgeons. During that 3-months period, 487 "hits" encountered in 298 colonoscopies. Polypectomies were performed for 51.3% and 68.4% of these polypectomies were adenomas on histology. The post-intervention median ADR was 30.4% was higher than the median baseline polypectomy rate of 24.3% (p = 0.02). Of the adenomas excised, 14 (5.6%) were sessile serrated adenomas. Of those who performed ≥ 5 AI-aided colonoscopies, 13 (72.2%) had an improvement of ADR compared to their polypectomy rate before the introduction of AI, of which 2 of them had significant improvement., Conclusions: Real-time AI-aided colonoscopy have the potential to improved ADR even for experienced endoscopists and would therefore, improve the quality of colonoscopy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Availability of transient elastography (TE) limits the application of Baveno-VI criteria. In a derivation study, the ABP criteria (Albumin >40 g/l, Bilirubin <22 μmol/l and Platelet >114,000/μl) had been shown to perform well in identifying compensated advanced chronic liver disease (cACLD) patients without high-risk varices (HRV). We aim to externally validate this novel ABP criteria for the exclusion of HRVs among cACLD patients., Methods: Data was retrospectively collected from consecutive cACLD patients with paired TE and esophagogastroduodenoscopy (EGD) performed between 2011 and 2017 in Changi General Hospital, Singapore. We estimate the discriminative ability of ABP criteria in validation cohort using AUROC and calibration-in-the-large. We subsequently compare the performance between ABP and Baveno-VI criteria in the validation cohort., Results: Among 314 patients included in our validation cohort, 32 (10.2%) had HRV on screening EGD. Application of ABP criteria within this validation cohort has increased discriminative ability than the derivation cohort. The AUROC of validation and derivation cohort were 0.68 (0.60-0.76) and 0.66 (0.60-0.76), respectively. The mean and standard error for calibration-in-the-large and calibration slope were -0.08 (0.22) and 0.93 (0.26) respectively. The ABP criteria had excellent performance in excluding HRV and will spare more screening EGDs than the Baveno-VI criteria (39.2% vs 27.4%, p < 0.001), without missing more HRVs., Conclusion: We validated the performance of ABP criteria for the exclusion of HRVs in cACLD patients. ABP criteria is superior to Baveno-VI criteria by sparing more screening EGD without the need of TE., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction and Aim: Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD., Methods: We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy., Result: From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27)., Conclusion: Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans., Methods: We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water., Results: ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo., Conclusions: ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes., Competing Interests: Sponsorship of this study by Elomart Pte Ltd does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background/aims: Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore., Methods: In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013-2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types., Results: A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001)., Conclusion: In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.

Aims: Advanced fibrosis (AF) and liver cirrhosis (LC) are important milestones in non-alcoholic fatty liver disease (NAFLD). FIB-4, NFS and BARD are validated scores with good accuracy in detecting AF and LC. APRI does not have similar predictive accuracy. While a modification (m-APRI) improves its use in viral hepatitis, this has yet to be evaluated in NAFLD. This study compares diagnostic performance of aforementioned scores in predicting AF and LC in NAFLD., Methods: Consecutive NAFLD patients undergoing Transient Elastography (TE) using Echosens® Fibroscan® for fibrosis staging were included. Cut-off liver stiffness measurements for AF and LC were 7.9 kPa and 11.5 kPa respectively. Anthropometric and laboratory tests done within 3 months were used. Diagnostic performances of scores were analyzed by standard statistical tests., Results: 161 patients qualified for the study. Mean age was 60.2 ± 14 years, BMI 26.8 ± 4.6 kg/m 2 . M-probe was used in 113, XL in 48. Optimal cut-offs of m-APRI for AF and LC were 5.84 and 9 respectively. Area under receiver operator characteristic curves (AUROC) for prediction of AF at optimal cut-off points were m-APRI 0.84, APRI 0.80, FIB-4: 0.77, NFS 0.77 and BARD 0.65. For prediction of LC, AUROC were m-APRI: 0.83, APRI: 0.76, FIB-4: 0.81, NFS: 0.77 and BARD: 0.66. m-APRI was significantly superior to all scores compared in detecting AF (p < 0.05 for all) and superior to APRI (p = 0.008) and BARD (p = 0.007) in predicting LC. There was no significant difference between m-APRI and FIB-4 or NFS in prediction of LC., Conclusions: For prediction of AF in NAFLD, m-APRI outperforms BARD, APRI, NFS and FIB-4, while for the prediction of cirrhosis, m-APRI is superior to APRI and BARD but comparable to NFS and FIB-4., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background and Aim: Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients., Methods: We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization., Results: A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed., Conclusion: The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction and Objectives: The novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19., Methods: We performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24 th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model., Results: Among 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I 2  = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I 2  = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I 2  = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I 2  = 71%) were higher subjects in critical COVID-19., Conclusion: COVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background and study aims  Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods  A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results  Two hundred and forty-seven colonoscopy procedures were analyzed. Baseline demographics and indications for colonoscopy of patients in both groups were similar. There were no significant differences in median TTC (10.0 vs 10.0 min, P  = 0.524) or total procedure time (22.5 vs 23.0 min, P  = 0.946) between colonoscopy performed in SPPE and EPPE. The ADR, PDR and CIR were also similar. Conclusion  Our findings suggest that use of EPPE does not affect colonoscopy performance., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Background and study aims  Published data on blue laser imaging (BLI) for detection and differentiation of colonic polyps are limited compared to narrow band imaging (NBI). This study investigated whether BLI can increase the detection rate of colonic polyps and adenomas when compared to white light imaging (WLI), and examined use of NICE (NBI International Colorectal Endoscopic) and JNET (Japan NBI Expert Team) classifications with BLI. Patients and methods  Patients aged 50 years and above referred for colonoscopy were randomized to BLI or WLI on withdrawal. Detected polyps were characterized using NICE and JNET classifications under BLI mode and correlated with histology. Primary outcome was adenoma detection rate. Secondary outcomes were utility of NICE and JNET classifications to predict histology using BLI. Results  A total of 182 patients were randomized to BLI (92) or WLI (90). Comparing BLI with WLI, the polyp detection rate was 59.8 % vs 40.0 %, P  = 0.008, and the adenoma detection rate was 46.2 % vs 27.8 %, P  = 0.010. NICE 1 and JNET 1 diagnosed hyperplastic polyps with sensitivity of 87.18 % and specificity of 84.35 %. NICE 2 diagnosed low- (LGD) or high-grade dysplasia (HGD) with sensitivity of 92.31 % and specificity of 77.45 %. JNET 2A diagnosed LGD with sensitivity of 91.95 %, and specificity of 74.53 %. Four cases of focal HGD all had JNET 2A morphology. Conclusion  BLI increased adenoma detection rate compared to WLI. NICE and JNET classifications can be applied when using BLI for endoscopic diagnosis of HP and LGD but histological confirmation remains crucial.

Background: Chronic hepatitis C infection is common among people with history of substance use. Liver fibrosis assessment is a barrier to linkage to care, particularly among those with history of substance users. The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination, especially in countries where transient elastography (TE) is not available. We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population., Methods: HCV patients with history of substance use between 2011 and 2016 were analyzed. All patients had TE for liver fibrosis assessment. Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared. Youden's index was used to determine optimal cut-off of the novel score., Results: A total of 579 patients were included. In multivariate logistic regression, cirrhosis on TE was associated with age (P = 0.002), aspartate aminotransferase (AST) (P = 0.004), and platelet count (P < 0.001), but not alanine aminotransferase (ALT) (P = 0.896). These form the components of modified AST-to-platelet ratio index (APRI) score. Modified APRI was superior to APRI in predicting cirrhosis (AUROC, 0.796 vs. 0.770, P = 0.007), but not fibrosis-4 score (FIB-4) (P = 1.00). Modified APRI at cut-off of 4 has sensitivity, specificity and negative predictive value (NPV) of 94.4%, 26.9% and 92.6%, respectively, and at 19, has sensitivity, specificity and positive predictive value (PPV) of 33.3%, 96.2% and 77.1%, respectively. FIB-4 has a NPV and PPV of 88.6%, 41.8% and 78.5%, 77.6%, at cut-off of 1.45 and 3.25, respectively. Using the cut-off of 4 and 14 for modified APRI, 32.5% of patients can be correctly classified and misses out only 5.6% of cirrhosis patients., Conclusions: Modified APRI score is superior in predicting cirrhosis in HCV population, with 32.5% of the population being correctly classified using cut-off of 4 and 14. Further studies are required to validate the findings., (Copyright © 2018. Published by Elsevier B.V.)

Background and Aim: The prohibitively high cost of direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection remains a barrier to treatment access in Singapore. We aimed to evaluate whether DAA as first-line therapy would be cost-effective for genotype 3 (GT3) HCV patients compared with pegylated interferon and ribavirin (PR)., Methods: A decision tree analysis was used to compare the costs and outcomes of DAA and PR as first-line therapy. Treatment effectiveness, defined as sustained virological response, was assessed using a retrospective cohort of treated GT3 HCV patients. Direct medical costs were estimated from the payer's perspective using billing information. We obtained health utilities from published literature. We performed extensive one-way sensitivity analyses and probabilistic sensitivity analyses to account for uncertainties regarding the model parameters., Results: In base case analysis, first-line therapy with DAA and PR yielded quality-adjusted life years (QALYs) of 0.69 and 0.62 at a cost of USD 54 634 and USD 23 857, respectively. The resultant incremental cost-effectiveness ratio (ICER) (USD 449 232/QALY) exceeded the willingness-to-pay threshold (USD 53 302/QALY). The ICER was robust for uncertainties regarding the model parameters. The cost of DAA is the key factor influencing the cost-effectiveness of HCV treatment. At current price, DAA as first-line therapy is not cost-effective compared with PR, with or without consideration of retreatment. Threshold analysis suggested that DAA can be cost-effective if it costs less than USD 17 002 for a 12-week treatment course., Conclusion: At current price, DAA as first-line therapy is not cost-effective compared with PR in GT3 HCV patients in Singapore.

Context: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and associated with significant morbidity and mortality. Thyroid hormone (TH) increases β-oxidation of fatty acids and decreases intrahepatic lipid content (IHLC) in rodents with NAFLD., Objective: We investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans., Design/setting: This was a phase 2b single-arm study in six hospitals in Singapore. Intrahepatic thyroid hormone concentrations were measured in rats with induced NAFLD., Patients: Euthyroid patients with T2DM and steatosis measured by ultrasonography., Intervention: Levothyroxine was titrated to reach a thyroid-stimulating hormone level of 0.34 to 1.70 mIU/L before a 16-week maintenance phase., Main Outcome Measures: The primary outcome measure was change in IHLC measured by proton magnetic resonance spectroscopy after treatment., Results: Twenty male patients were included in the per-protocol analysis [mean ± SD: age, 47.8 ± 7.8 years; body mass index (BMI), 30.9 ± 4.4 kg/m2; baseline IHLC, 13% ± 4%]. After treatment, IHLC was decreased 12% (±SEM, 26%) relative to baseline (absolute change, -2%; 95% CI, -3 to 0; P = 0.046). Small decreases in BMI (P = 0.044), visceral adipose tissue volume (P = 0.047), and subcutaneous adipose tissue volume (P = 0.045) were observed. No significant changes in glucose regulation or lipid profile occurred., Conclusion: This study demonstrated the efficacy and safety of low-dose TH therapy for NAFLD in men. TH or TH analogs may be beneficial for this condition.

Background and Aims: Wire-guided biliary cannulation has been demonstrated to improve cannulation rates and reduce post-ERCP pancreatitis (PEP), but the impact of wire caliber has not been studied. This study compares successful cannulation rates and ERCP adverse events by using a 0.025-inch and 0.035-inch guidewire., Methods: A randomized, single blinded, prospective, multicenter trial at 9 high-volume tertiary-care referral centers in the Asia-Pacific region was performed. Patients with an intact papilla and conventional anatomy who did not have malignancy in the head of the pancreas or ampulla and were undergoing ERCP were recruited. ERCP was performed by using a standardized cannulation algorithm, and patients were randomized to either a 0.025-inch or 0.035-inch guidewire. The primary outcomes of the study were successful wire-guided cannulation and the incidence of PEP. Overall successful cannulation and ERCP adverse events also were studied., Results: A total of 710 patients were enrolled in the study. The primary wire-guided biliary cannulation rate was similar in 0.025-inch and 0.035-inch wire groups (80.7% vs 80.3%; P = .90). The rate of PEP between the 0.025-inch and the 0.035-inch wire groups did not differ significantly (7.8% vs 9.3%; P = .51). No differences were noted in secondary outcomes., Conclusion: Similar rates of successful cannulation and PEP were demonstrated in the use of 0.025-inch and 0.035-inch guidewires. (Clinical trial registration number: NCT01408264.)., (Copyright © 2018. Published by Elsevier Inc.)

Background: There is no consensus on what constitutes adequate training for needle knife precut sphincterotomy., Objective: The purpose of this study was to determine the number of procedures required before effective and safe precut sphincterotomy can be achieved., Methods: This retrospective study examined the cumulative experience of a single endoscopist from January 2006-December 2015. Precut sphincterotomy success and complication rates were analyzed as a function of number of procedures performed. Acceptable success and complication rates were defined as 85% and 10% respectively. A one-sided binomial test was used to test success and complication rates of every 25 precut sphincterotomies performed., Results: The index endoscopic retrograde cholangiopancreatography was successful in 141/158 (89.2%) patients who underwent precut sphincterotomy. This increased to 148/158 (93.7%) when endoscopic retrograde cholangiopancreatography was repeated on another day. Six precut sphincterotomies were required to achieve an 85% success probability. This was maintained consistently above 85% after 13 precuts, and was significantly higher (91.2%; p  = 0.029) than 85% at the 125th precut. Bleeding and pancreatitis developed in 2/158 (1.3%) and 5/158 (3.2%). Probability of either complications remained below 5% after 50 precuts. No perforation occurred., Conclusion: At least 13 precut sphincterotomies were required to achieve a sustained success rate greater than 85%. The probability of bleeding or pancreatitis was less than 5% after 50 precut sphincterotomies.

Background and aim: Conventional hepatitis C treatment using pegylated interferon (PEG-IFN) and ribavirin is associated with significant side effects. IL28B polymorphism can predict response to treatment, with CC genotype having a better response. ITPA gene deficiency protects against clinically significant anaemia induced by treatment. The purpose of this study was to determine IL28B polymorphism and ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response (SVR). Methods: All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study. Blood samples for IL28B and ITPA genotyping were obtained. Medical records were reviewed for verification of treatment response, development of anaemia and if treatment reduction was required during the treatment. Results: A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin, of whom 42 agreed to participate in the study. Mean age was 45.6±12.9 years at time of treatment, and 83.3% of patients were males. Thirty-three (78.6%) had IL28B CC genotype, of whom 25 (75.8%) obtained SVR compared with only 3 of 9 (33.3%) non C/C genotype patients who achieved SVR ( P =0.041). Eleven (26.1%) patients had ITPA AC genotype, and 30 (71.4%) had CC genotype. There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia (45.5% vs 63.3%, P =0.302). Even among patients who developed anaemia, 70.8% still managed to achieve SVR. Treatment reduction also had no impact on SVR. Conclusion: Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.

Background: Antibiotic resistance is an important cause of H. pylori treatment failure. This study aimed to examine the change in H. pylori antibiotic resistance profile in Singapore over the course of 15 years., Materials and Methods: The study period was from 2000 to 2014. Gastric mucosal biopsies obtained from H. pylori-positive patients were cultured. Antibiotic susceptibility to metronidazole, clarithromycin, levofloxacin, tetracycline, and amoxicillin was tested. The change in resistance rates over time was analyzed., Results: A total of 708 H. pylori isolates were cultured. There was a significant increase in resistance rates for metronidazole (2000-2002: 24.8%; 2012-2014: 48.2%; p < .001), clarithromycin (2000-2002: 7.9%; 2012-2014: 17.1%; p = .022), and levofloxacin (2000-2002: 5%; 2012-2014: 14.7%; p = .007). The resistance rates for tetracycline (2000-2002: 5%; 2012-2014: 7.6%) and amoxicillin (2000-2002: 3%; 2012-2014: 4.4%) remained stable. Increase in dual (2000-2002: 6.9%; 2012-2014: 9.4%; p = .479) and triple antibiotic resistance rates (2000-2002: 0; 2012-2014: 7.6%; p < .001) were observed. Overall, the most common dual and triple resistance patterns were metronidazole/clarithromycin (4.4%) and metronidazole/clarithromycin/levofloxacin (1.8%), respectively., Conclusions: Over 15 years, H. pylori resistance rates to metronidazole, clarithromycin and levofloxacin had increased. There was increased resistance to multiple antibiotics., (© 2016 John Wiley & Sons Ltd.)

Cancers are among the leading causes of morbidity and mortality worldwide, with gastrointestinal (GI) luminal cancers accounting for a large proportion of cancer incidence. Chemoprevention of GI luminal cancers is important to reduce this cancer burden. Screening for and eradication of Helicobacter pylori (H. pylori) in areas with high gastric cancer incidence is a safe and effective strategy to decrease the incidence of gastric cancer. Eradication of H. pylori also seems to be effective in preventing metachronous cancer development after endoscopic resection of early gastric cancer. For the average risk individual, COX inhibitors may have a role in reducing the incidence of adenoma formation as well as colorectal cancer, bearing in mind its inherent risks. There is currently insufficient evidence to recommend a chemoprevention agent against esophageal and small intestine cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Narrow band imaging (NBI) is generally considered to be useful for lesion characterization, but not enhanced detection of gastric lesions, because of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI or 290-NBI), which is twice as bright as the previous version, would improve detection of premalignant gastric lesions compared with high-definition white light endoscopy (HD-WLE)., Patients and Methods: This was a multicenter prospective randomized study involving five tertiary institutions in the Asia-Pacific region. A total of 579 patients aged older than 50 years who underwent diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal gastric lesions, and gastric cancers., Results: Focal gastric lesions were detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI, respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and in 52/293 patients (17.7%) by NBI (P<0.001). Gastric cancer were found in 7/286 (2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189)., Conclusion: NBI increased the detection rate of IM compared with HD-WLE.

Aim: To examined the efficacy and safety of treatment with boceprevir, PEGylated-interferon and ribavirin (PR) in hepatitis C virus genotype 1 (HCVGT1) PR treatment-failures in Asia., Methods: The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures. Participating physicians were invited to contribute data from their patients: baseline characteristics, on-treatment responses, sustained virological response at week 12 (SVR12), and safety were collected and analysed. Multivariate analysis was performed to determine predictors of response., Results: 150 patients were enrolled from Australia, Malaysia, Singapore and Thailand (Asians = 86, Caucasians = 63). Overall SVR12 was 61% (Asians = 59.3%, Caucasians = 63.5%). SVR12 was higher in relapsers (78%) compared with non-responders (34%). On-treatment responses predicted SVR, with undetectable HCVRNA at week 4, 8 and 12 leading to SVR12s of 100%, 87%, and 82% respectively, and detectable HCVRNA at week 4, 8 and 12, leading to SVR12s of 58%, 22% and 6% respectively. Asian patients were similar to Caucasian patients with regards to on-treatment responses. Patients with cirrhosis (n = 69) also behaved in the same manner with regards to on-treatment responses. Those with the IL28B CC genotype (80%) had higher SVRs than those with the CT/TT (56%) genotype (P = 0.010). Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR. Serious adverse events occurred in 18.6%: sepsis (2%), decompensation (2.7%) and blood transfusion (14%). Discontinuations occurred in 30.7%, with 18.6% fulfilling stopping rules., Conclusion: Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80% if they have good on-treatment responses; however, discontinuations occurred in 30% because of virological failure or adverse events.

Background and Aim: Clarithromycin-based triple therapy (TT) is the first-line treatment for Helicobacter pylori infection in Singapore. There is awareness that TT may no longer be effective due to increased clarithromycin resistance rates. Sequential therapy (ST) and concomitant therapy (CT) are alternative treatment regimens. This study aimed to compare the efficacy of 10-day TT, ST, and CT as first-line treatment for H. pylori infection., Methods: A randomized study conducted in a teaching hospital. Patients aged 21 years and older with newly diagnosed H. pylori infection were randomized to 10-day TT, ST, or CT. Treatment outcome was assessed by 13-carbon urea breath test at least 4 weeks after therapy. Intention to treat (ITT), modified ITT (MITT), and per protocol (PP) analyses of the eradication rates were performed., Results: A total of 462 patients were enrolled (ST: 154; TT 155; CT 153). Patient demographics were similar. Eradication rates for ST versus TT versus CT: ITT analysis: 84.4% versus 83.2% versus 81.7% (P = not significant [NS]); MITT analysis: 90.3% versus 92.1% versus 94.7% (P = NS); PP analysis: 94.1% versus 92.8% versus 95.4% (P = NS). Antibiotic resistance rates for amoxicillin, clarithromycin, and metronidazole were 4.7%, 17.9%, and 48.1%, respectively. Dual clarithromycin and metronidazole resistance occurred in 7.5%. Dual resistance and lack of compliance were predictors of treatment failure., Conclusions: TT, ST, and CT all achieved eradication rates above 80% on ITT and above 90% on MITT and PP analyses. Dual resistance and lack of compliance were predictors of treatment failure (clinicaltrials.gov: NCT02092506)., (© 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Wireless oesophageal (Bravo) readings in healthy European and American subjects show varied results. Values in Asians remain unstudied., Aims: We performed Bravo studies in healthy Asians to determine if values differed from previously published and identified reflux parameters to differentiate healthy volunteers from patients., Methods: Fifty healthy volunteers were recruited between August 2009 and August 2011 to undergo 48 h wireless pH monitoring. Bravo capsule was introduced transorally and placed 6 cm above the squamocolumnar junction. Acid reflux parameters were compared against 41 patients previously evaluated for non-erosive reflux disease., Results: Five volunteers were excluded. Capsule dislodgement occurred in four and three volunteers on study days 1 and 2 respectively. Forty and 37 volunteers (73% male, mean age 33.0 ± 7.6 years) had interpretable readings at 24 and 48 h, respectively. Percentage of time oesophageal pH<4 in 37 volunteers who completed 48 h recordings was 1.6% (7.5%), 1.5% (6.3%) and 1.9% (5.8%) on days 1, 2 and overall study duration, respectively., Conclusion: Bravo readings in Asians differed from previously published. Percentage of time oesophageal pH<4 on day 2 and DeMeester score on day 2 (95th percentile 22.9) best discriminated healthy volunteers from patients., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Endoscopic transenteric stenting is the standard treatment for pseudocysts, but it may be inadequate for treating infected collections with solid debris. Surgical necrosectomy results in significant morbidity. Direct endoscopic necrosectomy (DEN), a minimally invasive treatment, may be a viable option. This study examined the efficacy and safety of DEN for the treatment of infected walled-off pancreatic necrosis and infected pseudocysts with solid debris., Methods: This study was a retrospective analysis of data collected from a prospective database of patients who underwent DEN in the presence of infected walled-off pancreatic necrosis or infected pseudocysts with solid debris from April 2007 to October 2011. DEN was performed as a staged procedure. Endoscopic ultrasonography-guided transgastric stenting was performed during the first session for initial drainage and to establish endoscopic access to the infected collection. In the second session, the drainage tract was dilated endoscopically to allow transgastric passage of an endoscope for endoscopic necrosectomy. Outcome data included technical success, clinical success and complication rates., Results: Eight patients with infected walled-off pancreatic necrosis or infected pseudocysts with solid debris (mean size 12.5 cm; range 7.8-17.2 cm) underwent DEN. Underlying aetiologies included severe acute pancreatitis (n = 6) and post-pancreatic surgery (n = 2). DEN was technically successful in all patients. Clinical resolution was achieved in seven patients. One patient with recurrent collection opted for surgery instead of repeat endotherapy. No procedural complications were encountered., Conclusion: DEN is a safe and effective minimally invasive treatment for infected walled-off pancreatic necrosis and infected pseudocysts.

Objective: This study was aimed to assess whether the efficacy of one-week triple therapy comprising of proton pump inhibitor, amoxicillin and clarithromycin (PPI/A/C) on Helicobacter pylori (H. pylori) infection in Singapore has decreased over the duration from 2005 to 2010., Methods: The clinical data of H. pylori-positive patients treated with one-week PPI/A/C in 2005 and 2010 were reviewed retrospectively using a registry database. The primary endpoint was the difference in treatment success rate., Results: A total of 465 patients (n = 174 in 2005 and n = 291 in 2010) were analyzed. In 2010, compared with 2005, the mean age of patients was younger (47 vs 56 years, P < 0.001) and the proportion of foreigners was higher (19.9% vs 5.7%, P < 0.001). The success rate of H. pylori eradication remained similar over the two time periods (90.2% in 2005 vs 88.7% in 2010, P = 0.597). Multinomial logistic regression revealed that mean age, gender, diagnosis and nationality had no impact on the success of H. pylori eradication., Conclusions: From 2005 to 2010, there was no significant decrease in the efficacy of one-week PPI/A/C for the treatment of H. pylori infection. This treatment regime remained an effective first-line therapy for H. pylori infection in Singapore., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background: Patients with recurrent nonvariceal upper gastrointestinal bleeding who have failed endoscopic therapy pose a challenge. Percutaneous transcatheter angiographic embolization (TAE) is an alternative to surgery but remains controversial. This study compares the treatment outcomes in patients with recurrent nonvariceal upper gastrointestinal bleeding., Methods: A retrospective single-centre study of consecutive patients who underwent TAE (January 2007-December 2010) compared with patients treated surgically (January 2004-December 2010) was conducted. Patient demographics, comorbidities, rebleeding rates, length of stay and mortality were compared., Results: Thirty [23 men; age (SD) 66.5±15.6 years] and 63 [41 men; age (SD) 68.2±15.0 years, NS] patients underwent TAE and surgery after a mean (SD) of 1.7±1.0 and 2.1±1.1 (NS) gastroscopies, respectively, for gastric ulcers (n=28), duodenal ulcers (n=53), small-bowel diverticuli (n=7), jejunal ulcer (n=1) and gastric Dieulafoy's lesions (n=2). Ten (33.3%) and 44 (69.8%) patients who underwent TAE and surgery, respectively, had an American Society of Anesthesiologists status of at least 2 (P=0.001). Higher rebleeding rates were observed after TAE compared with surgery [n=14 (46.7%) vs. 8 (12.7%), P=0.001]; however, there were no significant differences in 30-day mortality (16.7 vs. 19.0%, NS), complication rates (46.7 vs. 60.3%, NS) and length of stay (45.1±9.8 vs. 25.5±18.1 days, P=0.06). Twenty-four out of 30 patients (80%) who underwent TAE achieved haemostasis after a median (SD) of 2.0 (1.2) TAE procedures. Rebleeding occurred in five out of seven patients (71%) who underwent TAE for small-bowel diverticular bleeding., Conclusion: TAE averted the need for surgery in high-risk patients. Its role in low surgical risk patients or patients with small-bowel diverticular bleeding requires further study.