Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Seven-day vonoprazan-based triple therapy as first-lineHelicobacter pylori treatment in comparison with extended sequential therapy.

Background and Aim: Vonoprazan as a new acid blocker has more potency and longer lasting acid suppression than proton pump inhibitors. Whether the efficacy of vonoprazan-based triple therapy is comparable with or even better than that of currently recommended first-line therapies is still unknown. Our study aims to compare the eradication rate and major adverse effects between 7-day vonoprazan-based triple therapy with high-dose amoxicillin and 14-day extended sequential therapy. Methods: We performed a retrospective analysis from the database of 13C-urea breath test at Fu Jen Catholic University Hospital. All patients with a definite diagnosis of Helicobacter pylori infection by rapid urease test, urea breath test, stool antigen test, or pathology report were recruited. Patients receiving first-line regimens with vonoprazan-based triple therapy or extended sequential therapy were included. The respective eradication rate determined by 13C-urea breath test and major adverse effects were demonstrated. Results: Totally, 106 patients were recruited in the vonoprazan-based triple therapy group and 357 in the extended sequential therapy group. There was no significant difference in eradication rate between vonoprazan-based triple therapy with high-dose amoxicillin and extended sequential therapy (83.0 vs 88.8%, P = 0.12). Major adverse effects occurred in 13 of the extended sequential therapy group but none in the other group (0% vs 3.6%, P = 0.046). Conclusions: Seven-day vonoprazan-based triple therapy with high-dose amoxicillin is a potential first-line anti-Helicobacter pylori regimen alternative to current standard treatment, with the advantages of simplicity, short treatment duration, low pill burden, and fewer major adverse effects.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

BACKGROUND: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking. OBJECTIVE: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population. DESIGN: Multicenter randomized controlled study. (ClinicalTrials.gov: NCT03373136). SETTING: 6 sites in Taiwan, July 2018 through July 2020. PARTICIPANTS: Participants aged 40 years or older with polyps of 4 to 10 mm. INTERVENTION: CSP or HSP to remove polyps of 4 to 10 mm. MEASUREMENTS: The primary outcome was the delayed bleeding rate within 14 days after polypectomy. Severe bleeding was defined as a decrease in hemoglobin concentration of 20 g/L or more, requiring transfusion or hemostasis. Secondary outcomes included mean polypectomy time, successful tissue retrieval, en bloc resection, complete histologic resection, and emergency service visits. RESULTS: A total of 4270 participants were randomly assigned (2137 to CSP and 2133 to HSP). Eight patients (0.4%) in the CSP group and 31 (1.5%) in the HSP group had delayed bleeding (risk difference, -1.1% [95% CI, -1.7% to -0.5%]). Severe delayed bleeding was also lower in the CSP group (1 [0.05%] vs. 8 [0.4%] events; risk difference, -0.3% [CI, -0.6% to -0.05%]). Mean polypectomy time (119.0 vs. 162.9 seconds; difference in mean, -44.0 seconds [CI, -53.1 to -34.9 seconds]) was shorter in the CSP group, although successful tissue retrieval, en bloc resection, and complete histologic resection did not differ. The CSP group had fewer emergency service visits than the HSP group (4 [0.2%] vs. 13 [0.6%] visits; risk difference, -0.4% [CI, -0.8% to -0.04%]). LIMITATION: An open-label, single-blind trial. CONCLUSION: Compared with HSP, CSP for small colorectal polyps significantly reduces the risk for delayed postpolypectomy bleeding, including severe events. PRIMARY FUNDING SOURCE: Boston Scientific Corporation.

Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan.

BACKGROUND: Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. METHODS: Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. RESULTS: All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI) 92.1-99.0%) and 100% (95% CI 96.4-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. CONCLUSIONS: SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs. CLINICAL TRIALS REGISTRATION: The study was not a drug trial. There was no need for clinical trial registration.

Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters. METHODS: We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured by 13C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis. The microbiota composition and antibiotic resistome of faecal samples collected at baseline (before treatment) and at 2 weeks, 8 weeks, and 1 year after eradication therapy was profiled by shotgun metagenomic sequencing and 16S rRNA gene sequencing. The frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants with available data. The trial is complete and registered with ClinicalTrails.gov, NCT03148366. FINDINGS: Between Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10-10) at week 2, which were restored to pretreatment level by week 8. The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin-sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year. The frequency of any adverse effects was significantly higher after BQ10 therapy (211 [77%] of 273 participants) than after EAML14 therapy (134 [48%] of 277; p<0·0001). INTERPRETATION: We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy. FUNDING: The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Dedicated staff for patient education improves bowel preparation quality and reduces the cecal intubation time of colonoscopy: A single institution retrospective study.

Adequate bowel preparation is an essential part of a high-quality colonoscopy. Recent studies showed that the small-volume bowel cleansing agent Bowklean performs better in terms of tolerability and acceptability. However, its split-dose regimen is sometimes confusing to the patient. To promote Bowklean in Fu Jen Catholic University Hospital, dedicated staff for patient education on bowel preparation were provided by Universal Integrated Corporation (Taiwan), but not in every period because of the clinic room availability and manpower capacity. This provided us an opportunity to compare the quality of colonoscopy between those with and without the dedicated patient education. This study aimed to compare various quality indices between the two groups. We set bowel preparation quality as the primary endpoint, assessed by modified Aronchick scale, and other quality indices including procedure time and adenoma detection rate as the secondary endpoints. We performed a single institution retrospective study. All patients who received colonoscopy from an outpatient setting with Bowklean as the bowel cleansing agent from October 2020 to November 2020 were reviewed. Primary and secondary endpoints were then compared between the conventional group and the dedicated staff group, with StataSE 14 by Wilcoxon rank sum test or logistic regression. Four hundred ten patients were recruited, including 217 patients with dedicated patient education and 193 without. The proportion of bowel preparation quality "Excellent + Good + Fair" was significantly higher in dedicated staff group than conventional group (97.7% vs 93.3%, P = .03; logistic regression coefficient = 1.12). The cecal intubation time was significantly shorter in the dedicated staff group (3.68 ± 2.02 minutes vs 4.52 ± 3.25 minutes, P < .01). After excluding those with polypectomy or biopsy, the total procedure time tended to be shorter in the dedicated staff group (10.2 ± 3.35 minutes vs 9.40 ± 2.43 minutes, P = .06). There was no significant difference regarding adenoma detection rate between the two groups. Our study shows that patient education by dedicated staff can improve bowel preparation quality and has the potential to decrease procedure time. Further large-scale prospective trials are still needed to evaluate if it can also achieve a better adenoma detection rate.

Compositions of gut microbiota before and shortly after hepatitis C viral eradication by direct antiviral agents.

It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients (n = 42), with or without cirrhosis, and their age-and sex-matched controls (n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae, Peptostreptococcaceae, Staphylococcaceae, Morganellaceae, Pasteurellaceae, Succinivibrionaceae, and Moraxellaceae. Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.

Optimal Dietary Intake Composition of Choline and Betaine Is Associated with Minimized Visceral Obesity-Related Hepatic Steatosis in a Case-Control Study.

Few studies on humans have comprehensively evaluated the intake composition of methyl-donor nutrients (MDNs: choline, betaine, and folate) in relation to visceral obesity (VOB)-related hepatic steatosis (HS), the hallmark of non-alcoholic fatty liver diseases. In this case-control study, we recruited 105 patients with HS and 104 without HS (controls). HS was diagnosed through ultrasound examination. VOB was measured using a whole-body analyzer. MDN intake was assessed using a validated quantitative food frequency questionnaire. After adjustment for multiple HS risk factors, total choline intake was the most significant dietary determinant of HS in patients with VOB (Beta: -0.41, p = 0.01). Low intake of choline (<6.9 mg/kg body weight), betaine (<3.1 mg/kg body weight), and folate (<8.8 µg/kg body weight) predicted increased odds ratios (ORs) of VOB-related HS (choline: OR: 22, 95% confidence interval [CI]: 6.5-80; betaine: OR: 14, 95% CI: 4.4-50; and folate: OR: 19, 95% CI: 5.2-74). Combined high intake of choline and betaine, but not folate, was associated with an 81% reduction in VOB-related HS (OR: 0.19, 95% CI: 0.05-0.69). Our data suggest that the optimal intake of choline and betaine can minimize the risk of VOB-related HS in a threshold-dependent manner.

Risk of colonoscopy-related complications in a fecal immunochemical test-based population colorectal cancer screening program.

BACKGROUND: The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes. METHODS: Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy. RESULTS: 319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32). CONCLUSIONS: FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.

Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment.

OBJECTIVE: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5. DESIGN: 191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed. RESULTS: The SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations. CONCLUSION: SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis.

BACKGROUND/AIMS: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. METHODS: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. RESULTS: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). CONCLUSION: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Feasibility of Upper Gastrointestinal Examination in Home Care Setting with a Magnetically Assisted Capsule Endoscopy System: A Retrospective Study.

The magnetic assisted capsule endoscope (MACE) with a hand-held magnetic field navigator (MFN) for upper gastrointestinal examination achieved satisfactory results in a healthy volunteer study. We evaluated the feasibility of upper gastrointestinal examination in the home care setting with the MACE system. Home care patients with upper gastrointestinal symptoms that received an MACE exam were enrolled in the study. MACE procedure time; completeness of observation of important anatomical landmarks; endoscopic diagnosis; patient tolerance during the procedure; and patient data, including age, sex, comorbidities, symptoms, body weight, and height, were retrieved from hospital information system for data analysis. A total of 16 participants were enrolled with a mean age 74.3 ± 15.4 years (47 to 99 years). One patient failed to swallow the capsule and was excluded. The average procedure time was 23.7 ± 10.0 min (14.1 to 42.5 min) to complete each endoscopic exam for the remaining 15 patients. The overall maneuverability in the esophagus, stomach, and duodenum was 93.75%, 87.5%, and 75%, respectively. Overall completeness in the aforementioned regions was 93.75%, 81.25%, and 75%, respectively. No severe adverse events were noted. The results clearly demonstrate the promise of using this MACE system to perform endoscopic examination outside the hospital for patients confined to the community and home.

Multinational survey on the preferred approach to management of Barrett's esophagus in the Asia-Pacific region.

BACKGROUND: Major societies provide differing guidance on management of Barrett's esophagus (BE), making standardization challenging. AIM: To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists. METHODS: Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE. RESULTS: Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001). CONCLUSION: Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan.

BACKGROUND: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. METHODS: Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. RESULTS: The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6-96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8-99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. CONCLUSIONS: SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.

Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial.

BACKGROUND: Antiviral therapy for patients with non-cirrhotic chronic hepatitis B and minimally raised alanine aminotransferase (ALT) is controversial. We aimed to investigate the efficacy and safety of tenofovir disoproxil fumarate in reducing the risk of disease progression in this patient population. METHODS: TORCH-B is a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial done at six teaching hospitals in Taiwan that enrolled patients with chronic hepatitis B. Eligible patients were aged 25-70 years and had substantial viraemia (viral DNA >2000 IU/mL) and minimally raised serum ALT concentrations more than one-fold but less than two-fold the upper limit of normal (ULN). Exclusion criteria included liver cirrhosis and previous antiviral treatment. Eligible participants were randomly assigned (1:1), stratified by site with a fixed block size of ten, to receive either 300 mg of oral tenofovir disoproxil fumarate or placebo once daily for 3 years. The participants, investigators, research coordinators, pathologists, laboratory personnel, and staff involved in patient care or assessment were masked to treatment assignment. 0·5 mg/day of oral entecavir was added to rescue acute hepatitis flare. The coprimary outcomes were change in necroinflammation severity on the Knodell scale and change in fibrosis stage on the Ishak scale and were evaluated in the modified intention-to-treat population, which comprised all patients with paired liver biopsies. Safety was evaluated in all patients who were randomly assigned. This trial is registered at ClinicalTrials.gov, NCT01522625, and is completed. FINDINGS: From Jan 30, 2012, to Nov 10, 2015, 875 patients were screened and 160 were randomly assigned to receive either tenofovir disoproxil fumarate (n=79) or placebo (n=81). The coprimary outcomes were assessed in 146 patients (73 in each group). Liver fibrosis progressed (an increase of ≥1 stage) in 19 (26%, 95% CI 17-38) of 73 patients in the tenofovir disoproxil fumarate group and in 34 (47%, 35-59) of 73 patients in the placebo group (relative risk [RR] 0·56, 95% CI 0·35-0·88; p=0·013), whereas necroinflammation progressed (an increase of ≥2 points) in five (7%, 95% CI 2-15) patients in the tenofovir disoproxil fumarate group and in 12 (16%, 9-27) patients in the placebo group (RR 0·42, 95% CI 0·15-1·12; p=0·084). Two (3%) of 79 patients in the tenofovir disoproxil fumarate group and 13 (16%) of 81 patients in the placebo group had acute hepatitis flare requiring add-on entecavir (RR 0·16, 95% CI 0·04-0·68; p=0·013). The two groups were otherwise similar in occurrences of adverse events. No patients died. INTERPRETATION: Tenofovir disoproxil fumarate reduces the risk of progression in liver fibrosis in patients with chronic hepatitis B and minimally raised ALT, but its effect on necroinflammation is non-significant. FUNDING: The Taiwan Ministry of Science and Technology, E-Da Hospital, the Taipei Institute of Pathology, Gilead Sciences.

Comparison of the effect of clarithromycin triple therapy with or without N-acetylcysteine in the eradication of Helicobacter pylori: a randomized controlled trial.

BACKGROUND: Whether adjunctive N-acetylcysteine (NAC) may improve the efficacy of triple therapy in the first-line treatment of Helicobacter pylori infection remains unknown. Our aim was to compare the efficacy of 14-day triple therapy with or without NAC for the first-line treatment of H. pylori. MATERIAL AND METHODS: Between 1 January 2014 and 30 June 2018, 680 patients with H. pylori infection naïve to treatment were enrolled in this multicenter, open-label, randomized trial. Patients were randomly assigned to receive triple therapy with NAC [NAC-T14, dexlansoprazole 60 mg four times daily (q.d.); amoxicillin 1 g twice daily (b.i.d.), clarithromycin 500 mg b.i.d., NAC 600 mg b.i.d.] for 14 days, or triple therapy alone (T14, dexlansoprazole 60 mg q.d.; amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d.) for 14 days. Our primary outcome was the eradication rates by intention to treat (ITT). Antibiotic resistance and CYP2C19 gene polymorphism were determined. RESULTS: The ITT analysis demonstrated H. pylori eradication rates in NAC-T14 and T14 were 81.7% [276/338, 95% confidence interval (CI): 77.5-85.8%] and 84.3% (285/338, 95% CI 80.4-88.2%), respectively. In 646 participants who adhered to their assigned therapy, the eradication rates were 85.7% and 88.0% with NAC-T14 and T14 therapies, respectively. There were no differences in compliance or adverse effects. The eradication rates in subjects with clarithromycin-resistant, amoxicillin-resistant, or either clarithromycin/amoxicillin resistant strains were 45.2%, 57.9%, and 52.2%, respectively, for NAC-T14, and were 66.7%, 76.9%, and 70.0%, respectively, for T14. The efficacy of NAC-T14 and T14 was not affected by CYP2C19 polymorphism. CONCLUSION: Add-on NAC to triple therapy was not superior to triple therapy alone for first-line H. pylori eradication [ClinicalTrials.gov identifier: NCT02249546].

Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial.

BACKGROUND: In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4-86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7-88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6-92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters. METHODS: This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879. FINDINGS: Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p<0·0001), and BQ10 (p<0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p<0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% [15/127] to 66% [38/58] for T14, 7% [10/135] to 64% [28/44] for C10), cefazolin (13% [16/127] to 43% [25/58] for T14, 10% [13/135] to 41% [18/44] for C10), cefmetazole (8% [10/127] to 26% [15/58] for T14, 4% [5/135] to 18% [8/44] for C10), levofloxacin (8% [10/127] to 35% [20/58] for T14, 7% [10/135] to 32% [14/44] for C10), gentamicin (13% [19/146] to 47% [27/58] for T14, 15% [22/149] to 45% [20/44] for C10), and trimethoprim-sulfamethoxazole (33% [48/146] to 86% [50/58] for T14, 28% [42/148] to 86% [38/44] for C10; p<0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10. INTERPRETATION: Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk.

BACKGROUND: There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). AIM: To investigate if hepatitis B core-related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation. METHODS: This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score. RESULTS: During a median follow-up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5-year cumulative incidence of 56.1% (95% CI 46.7-66.0%) and 8.8% (95% CI 4.3-17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE-B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low-risk patients predicted by the score. CONCLUSIONS: Serum HBcrAg and HBsAg levels were independent predictors of off-NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.

The in vivo tissue effect of endoscopic balloon-based radiofrequency ablation in treating esophageal squamous cell neoplasia.

BACKGROUND: Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs). However, the in vivo tissue effects of RFA on the esophageal wall are uncertain. METHODS: We prospectively enrolled eight patients with flat-type early ESCNs who were treated with balloon-based RFA. We evaluated the in vivo tissue effect on the esophagus using endoscopic ultrasound (EUS) and the histology of retrieved coagulum. RESULTS: The mean tumor length was 6.1 cm, and six of the eight patients achieved a complete response after primary RFA. Real-time evaluation of the tissue effect showed that the mucosa and submucosal layer were more edematous and thicker after RFA than before the procedure (mean 4.89 vs. 2.04 mm, p<.001), suggesting that the thermal effect of RFA may injure the submucosa. Histological evaluation of retrieved coagulum showed a severe cauterization (burning) effect with extensive cell necrosis; however, four cases had some residual viable neoplastic cells. Even though there were viable cells in the sloughed coagulum, half of the patients still achieved complete remission after RFA. CONCLUSIONS: Our findings suggest that the thermal effect of RFA may injure the submucosal layer and enable neoplastic epithelium to slough off without "burning."