Hybrid, High-Dose Dual and Bismuth Quadruple Therapies for First-Line Treatment of Helicobacter pylori Infection in Taiwan: A Multicenter, Open-Label, Randomized Trial.

INTRODUCTION: The study aimed to compare the efficacies and safety of 14-day hybrid therapy, 14-day high-dose dual therapy, and 10-day bismuth quadruple therapy in the first-line treatment of Helicobacter pylori infections. METHODS: In this multicenter, open-label, randomized trial, we recruited adult H. pylori -infected patients from 9 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy. Eradication status was determined by the 13 C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS: Between August 1, 2018, and December 2021, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306; 95% confidence interval [CI] 88.4%-94.6%) for 14-day hybrid therapy, 83.3% (255/306; 95% CI 87.8%-95.0%) for 14-day high-dose dual therapy, and 90.2% (276/306; 95% CI 87.8%-95.0%) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference 8.2%; 95% CI 4.5%-11.9%; P = 0.002) and bismuth quadruple therapy (difference 6.9%; 95% CI 1.6%-12.2%; P = 0.012) were superior to high-dose dual therapy and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day high-dose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both P < 0.001). DISCUSSION: Fourteen-day hybrid therapy and 10-day bismuth quadruple therapy are more effective than 14-day high-dose dual therapy in the first-line treatment of H. pylori infection in Taiwan. However, high-dose dual therapy has fewer adverse effects than hybrid bismuth quadruple therapies.

REAP-HP survey 2020: Comparing the real-world practice and expectation in Helicobacter pylori eradication of the Taiwanese gastroenterologists in 2015 and 2020.

BACKGROUND: REAP-HP study (Real-world practice and Expectation of Asia-Pacific physicians and patients in Helicobacter Pylori eradication) was the pioneer study investigating the expectation and preference of physicians across Asia-Pacific in H. pylori eradication in 2015. This study is the first follow-up study of REAP-HP in Taiwan. AIMS: (1) To investigate the preference in regimens for the first-line anti-H. pylori therapy of Taiwanese gastroenterologist in 2020, (2) To survey the factor that cause the most concern when prescribing anti-H. pylori regimens in clinical practice, and (3) to compare REAP-HP survey data in 2020 and those surveyed in 2015 regarding the abovementioned end-points. METHODS: A questionnaire for H. pylori eradication survey of physicians was distributed to the gastroenterologists who attended the Taiwan Digestive Disease Week 2020. Data of most commonly used first-line anti-H. pylori regimens and concerned factors when prescribing anti-H. pylori regimens between 2015 and 2020 were compared. RESULTS: A total of 258 physicians from different districts of Taiwan participated in the REAP-HP Survey in 2020. The top three most commonly used anti-H. pylori regimens in Taiwan in 2020 were 14-day standard triple therapy (36.8%; 95% confidence interval [CI]: 30.9%-42.7%), 7-day standard triple therapy (17.8%; 95% CI: 13.1%-22.5%) and 14-day reverse hybrid therapy (14.7%; 95% CI: 10.4%-19.0%) respectively. The top two factors that cause the most concern during prescribing anti-H. pylori therapy were eradication rate (82.3%; 95% CI: 77.6%-87.0%) and side effect (10.4%; 95% CI: 6.7%-15.1%). In 2015, the top three most commonly used regimens in Taiwan were 7-day standard triple therapy (62%; 95% CI: 56.2%-67.8%), 14-day standard triple therapy (21%; 95% CI: 16.1%-25.9%) and 10-day sequential therapy (7%; 95% CI: 4%-10%). A remarkable difference of the most commonly used anti-H. pylori regimens between 2015 and 2020 existed (p < .001). The top two factors that cause the most concern during prescribing anti-H. pylori therapy in 2015 were eradication rate (84.1%) and side effect (7.0%). There were no differences in the factors that cause the most concern during prescribing anti-H. pylori regimens between 2015 and 2020. CONCLUSION: 14-day standard triple therapy has replaced 7-day standard triple therapy as the most commonly used first-line anti-H. pylori therapy among Taiwanese gastroenterologists in 2020. 14-day reverse hybrid therapy is on rise to the third place as the most commonly used anti-H. pylori regimen in Taiwan.

The efficacy of culture-guided versus empirical therapy with high-dose proton pump inhibitor as third-line treatment of Helicobacter pylori infection: A real-world clinical experience.

BACKGROUND AND AIM: Most consensuses recommend culture-guided therapy as third-line Helicobacter pylori treatment. This study aimed to investigate the efficacies of culture-guided therapy and empirical therapy with high-dose proton pump inhibitor (PPI) in the H. pylori third-line treatment. METHODS: Between August 2012 and October 2021, H. pylori-infected patients with at least two failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose rabeprazole and/or bismuth. They were categorized into three groups: patients who had positive results of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth quadruple therapy, patients who had positive results of culture with one or two susceptible antibiotics were treated by culture-guided bismuth-containing therapy, and patients who had a negative result of culture were treated by an empirical therapy with high-dose rabeprazole plus amoxicillin, tetracycline and levofloxacin. A post-treatment assessment was conducted at week 8. RESULTS: We recruited 126 patients. The eradication rates of culture-guided non-bismuth quadruple therapy (n = 50), culture-guided bismuth-containing therapy (n = 46) and empirical therapy (n = 30) were 84.0%, 87.0%, and 66.7% (95% confidence interval: 73.8-94.2%, 77.3-96.7%, and 49.8-83.6%), respectively. Overall, culture-guided therapy achieved a higher eradication rate than empirical therapy (85.4% vs 66.7%; 95% confidence interval, 0.4% to 37.0%, P = 0.022). CONCLUSIONS: Culture-guided therapy with high-dose PPI achieves a higher eradication rate than empirical therapy with high-dose PPI in the third-line treatment of H. pylori infection. The eradication rate of rescue therapy with bismuth plus two susceptible antibiotics is not inferior to that with three susceptible antibiotics.

Tailored susceptibility-guided therapy via gastric juice PCR for the first-line H. pylori eradication, a randomized controlled trial.

BACKGROUND/PURPOSE: Clarithromycin-based standard triple therapy is still commonly adopted by 81.4% of physicians in real-world practice but yields low eradication rates. Therefore, we conducted this study to compare the efficacy of gastric juice-guided therapy for first-line eradication with the standard triple therapy, in order to provide an alternative to real-world practice. METHODS: A total of 182 treatment-naïve Hp-infected patients were included and randomly allocated to either susceptibility-guided therapy (SGT) with gastric juice PCR or Clarithromycin-based standard triple therapy (STT) for 7 days. RESULTS: The intention-to-treat eradication rates were 89% (81/91) in SGT and 75.8% in STT (p < 0.031). The per-protocol eradication rates were 91.0% (81/89) in SGT and 79.3% (69/87) in STT (p < 0.034). Among the subgroups of different antibiotic resistance, patients with SGT demonstrated superior eradication rates (91.7% vs 45.5%, p < 0.027) in the subgroup of both clarithromycin resistance and levofloxacin resistance. CONCLUSION: This prospective randomized controlled trial demonstrated the reliable efficacy of susceptibility-guided therapy via gastric juice PCR for the first-line Hp eradication. In Asia-Pacific area, where standard triple therapy is still adopted by the majority of the physicians, it is a recommended alternative to overcome the increasing antibiotic resistance.

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users.

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Tetracycline-levofloxacin versus amoxicillin-levofloxacin quadruple therapies in the second-line treatment of Helicobacter pylori infection.

BACKGROUND: The Maastricht V/Florence Consensus Report recommends amoxicillin-fluoroquinolone triple or quadruple therapy as a second-line treatment for Helicobacter pylori infection. An important caveat of amoxicillin-fluoroquinolone rescue therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. The study aimed to investigate the efficacies of tetracycline-levofloxacin (TL) quadruple therapy and amoxicillin-levofloxacin (AL) quadruple therapy in the second-line treatment of H. pylori infection. METHODS: Consecutive H. pylori-infected subjects after the failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (tetracycline 500 mg QID, levofloxacin 500 mg QD, esomeprazole 40 mg BID, and tripotassium dicitrato bismuthate 300 mg QID) or AL quadruple therapy (amoxicillin 500 mg QID, levofloxacin 500 mg QD, esomeprazole 40 mg BID, and tripotassium dicitrato bismuthate 300 mg QID) for 10 days. Post-treatment H. pylori status was assessed 6 weeks after the end of therapy. RESULTS: The study was early terminated after an interim analysis. In the TL quadruple group, 50 out of 56 patients (89.3%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved only in 39 of 52 patients (69.6%) receiving AL quadruple therapy. Intention-to-treat analysis showed that TL quadruple therapy achieved a markedly higher eradication rate than AL quadruple therapy (95% confidence interval: 4.8% to 34.6%; p = 0.010). Further analysis revealed that TL quadruple therapy had a high eradication rate for both levofloxacin-susceptible and resistant strains (100% and 88.9%). In contrast, AL quadruple therapy yielded a high eradication for levofloxacin-susceptible strains (90.9%) but a poor eradication efficacy for levofloxacin-resistant strains (50.0%). The two therapies exhibited comparable frequencies of adverse events (37.5% vs 21.4%) and drug adherence (98.2% vs 94.6%). CONCLUSIONS: Ten-day TL quadruple therapy is more effective than AL quadruple therapy in the second-line treatment of H. pylori infection in a population with high levofloxacin resistance.

Taiwan nutritional consensus on the nutrition management for gastric cancer patients receiving gastrectomy.

Currently, consensus reports on the nutritional management for gastric cancer patients receiving gastric resection are lacking. The Gastroenterological Society of Taiwan therefore organized the Taiwan Gastric Cancer Nutritional Consensus Team to provide an overview of evidence and recommendations on nutritional support for gastric cancer patients undergoing gastrectomy. This consensus statement on the nutritional support for gastric cancer patients has two major sections:(1)perioperative nutritional support; and (2)long-term postoperative nutritional care. Thirty Taiwan medical experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. The key statements included that preoperative nutritional status affects the incidence of operative complications and disease-specific survival in gastric cancer patients undergoing gastrectomy. Following gastrectomy, both early oral and enteral tube feeding can result in a shorter stay than total parenteral nutrition. Compared to late oral feeding, early oral feeding can reduce hospital stay in gastric cancer patients receiving gastrectomy without an increase in complication rate. Routine supplementation with vitamin B12 is indicated for gastric cancer patients undergoing a total gastrectomy. Both high-dose oral vitamin B12 supplementation and intramuscular administration of vitamin B12 are equally effective in the treatment of vitamin B12 deficiency.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus.

OBJECTIVE: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. CONCLUSION: Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Severe acute exacerbation of HCV infection in cancer patients who undergo chemotherapy without antiviral prophylaxis.

No guidelines have been developed for the management of HCV-infected cancer patients receiving chemotherapy. The current study aimed to investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search for risk factors predicting severe acute exacerbation of HCV infection. This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analysed. Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = .003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV-infected haematological cancer patients was higher than that in those with HCC and non-HCC solid tumours (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and haematological malignancy were the risk factors related to the acute exacerbation (P < .001 and P = .004, respectively). None of the patients with severe acute HCV flares developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction. In conclusion, HCV infection increases the risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and haematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of haematological malignancy.

Detection and clinical characteristics of serrated polyps and conventional adenomas between patients in the outpatient and physical checkup unit receiving colonoscopy.

PURPOSE: The sessile serrated adenoma/polyp detection rate (SSA/PDR) among different colonoscopy indications from daily practice has not been fully understood. This study aimed to evaluate the detection and clinical characteristics of serrated polyps and conventional adenomas between outpatient department (OPD) and physical checkup unit (PCU) patients receiving colonoscopy. METHODS: The data for this retrospective study were collected between 2016 and 2017 at Kaohsiung Veterans General Hospital in Taiwan. A total of 7047 individuals were included, and information on polyp and adenoma detection was extracted from the colonoscopy reports. RESULTS: The adenoma detection rate, the SSA/PDR, and the detection rate of traditional serrated adenoma (TSA) were 32.2%, 0.60%, and 0.50%, respectively. Risk analysis revealed no significant difference (p = 0.095) in SSA/PDR between individuals < 50 years and ≥ 50 years, and no trend of increased SSA/PDR as age increased was observed (p = 0.320). SSA/P and TSA had higher risks for synchronous advanced neoplasia than conventional adenoma, but with proximal hyperplastic polyps lower (p < 0.001, respectively). No significant difference of SSA/PDR between OPD and PCU patients was observed (p = 1.000); however, the age of SSA/P was significantly older in OPD than in PCU patients (p = 0.048). CONCLUSION: The detection rates of CA and TSA were associated with age groups; however, SSA/PDR was insignificantly higher among individuals aged < 50 years than those with other age groups. In addition, SSA/PDR between OPD and PCU patients was not significantly found in daily practice of colonoscopies.

Equivalent efficacies of reverse hybrid and concomitant therapies in first-line treatment of Helicobacter pylori infection.

BACKGROUND AND AIM: Concomitant therapy is a recommended first-line treatment for Helicobacter pylori infection in most national or international consensuses. Reverse hybrid therapy is a modified 14-day concomitant therapy without clarithromycin and metronidazole in the final 7 days. This study aims to test whether 14-day reverse hybrid therapy is non-inferior to 14-day concomitant therapy in the first-line treatment of H. pylori infection. METHODS: Helicobacter pylori-infected adult patients were randomly assigned to receive either reverse hybrid therapy (dexlansoprazole 60 mg o.d. plus amoxicillin 1 g b.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.d. for initial 7 days) or concomitant therapy (dexlansoprazole 60 mg once o.d. plus amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg b.d. for 14 days). H. pylori status was assessed 6 weeks after the end of treatment. RESULTS: Helicobacter pylori-infected participants (n = 248) were randomized to receive either 14-day reverse hybrid therapy (n = 124) or 14-day concomitant therapy (n = 124). Intention-to-treat analysis demonstrated that the two therapies had comparable eradication rate (95.2% vs 93.5%; 95% confidence interval, -4.0% to 7.4%; P = 0.582). However, reverse hybrid therapy had a much lower frequency of adverse events than concomitant therapy (20.2% vs 38.7%, P = 0.001). The two therapies exhibited comparable drug adherence (93.5% vs 87.9%, P = 0.125). CONCLUSIONS: Fourteen-day reverse hybrid therapy and 14-day concomitant therapy are equivalent in efficacy for the first-line treatment of H. pylori infection. However, reverse hybrid therapy has fewer adverse events compared with concomitant therapy.

Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis.

BACKGROUND & AIMS: Gastric variceal bleeding (GVB) frequently recurs after hemostasis by gastric variceal obturation (GVO). We performed a multicenter, randomized controlled trial to determine the efficacy of carvedilol plus GVO in secondary prophylaxis of GVB. METHODS: We performed a prospective study of 121 patients with cirrhosis (ages 20-80 years) with GVB proven by endoscopy within 24 hours of bleeding and stable hemodynamics for at least 3 days after initial GVO. Patients were randomly assigned into a group that underwent repeated GVO (n = 61) or a group received repeated GVO plus carvedilol (n = 60). Recurrent GVB, upper gastrointestinal bleeding (UGIB), adverse events, and survival were compared between the groups. RESULTS: GVB recurred in 21 patients (34%) in the group that received repeated GVO and 14 patients (23%) in the group that received repeated GVO plus carvedilol (P = .18). Ascites (relative risk [RR], 2.69; 95% CI, 1.33-5.48; P = .006) and hepatoma (RR, 2.10; 95% CI, 1.03-4.28; P = .04) were associated with recurrent GVB. Twenty-nine patients (48%) in the group that received repeated GVO and 17 patients (28%) in the group that received repeated GVO plus carvedilol had recurrent UGIB (P = .03). Carvedilol (RR, 0.44; 95% CI, 0.24-0.80; P = .007) was associated with reduced risk of UGIB recurrence. Ascites (RR, 3.02; 95% CI, 1.59-5.73; P = .001) and hepatoma (RR, 2.07; 95% CI, 1.10-3.88; P = .02) were associated with recurrent UGIB. A higher proportion of patients in the group that received repeated GVO plus carvedilol (53%) had adverse events than the group that received repeated GVO (15%) (P < .001). Mean survival times were 21 ± 18 months in the group that received repeated GVO vs 25 ± 20 months in the group that received repeated GVO plus carvedilol (P = .30). CONCLUSION: In a randomized controlled trial, we found that addition of carvedilol to GVO did not decrease recurrence of GVB in patients with cirrhosis but was associated with decreased recurrence of UGIB. However, carvedilol plus GVO produced significantly more adverse events. Mean survival times did not differ significantly between groups. ClinicalTrials.gov no: NCT02504723.

Short-term and long-term impacts of Helicobacter pylori eradication with reverse hybrid therapy on the gut microbiota.

BACKGROUND AND AIMS: Anti-Helicobacter pylori therapy may lead to the growth of pathogenic or antibiotic-resistant bacteria in the gut. The study aimed to investigate the short-term and long-term impacts of H. pylori eradication with reverse hybrid therapy on the components and macrolide resistance of the gut microbiota. METHODS: Helicobacter pylori-related gastritis patients were administered a 14-day reverse hybrid therapy. Fecal samples were collected before treatment and at the end of week 2, week 8, and week 48. The V3-V4 region of the bacterial 16S rRNA gene in fecal specimens was amplified by polymerase chain reaction and sequenced on Illumina MiSeq platform. Additionally, amplification of erm(B) gene (encoding erythromycin resistance methylase) was performed. RESULTS: Reverse hybrid therapy resulted in decreased relative abundances of Firmicutes (from 62.0% to 30.7%; P < 0.001) and Actinobacteria (from 3.4% to 0.6%; 0.032) at the end of therapy. In contrast, the relative abundance of Proteobacteria increased from 10.2% to 49.1% (0.002). These microbiota alterations did not persist but returned to the initial levels at week 8 and week 48. The amount of erm(B) gene in fecal specimens was comparable with the pretreatment level at week 2 but increased at week 8 (0.025) and then returned to the pretreatment level by week 48. CONCLUSIONS: Helicobacter pylori eradication with reverse hybrid therapy can lead to short-term gut dysbiosis. The amount of erm(B) gene in the stool increased transiently after treatment and returned to the pretreatment level at 1-year post-treatment.

Fecal microbiota transplantation: Review and update.

Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.

Equivalent Efficacies of Reverse Hybrid and Bismuth Quadruple Therapies in Eradication of Helicobacter pylori Infection in a Randomized Controlled Trial.

BACKGROUND & AIMS: Bismuth quadruple therapy is recommended as a first-line treatment for Helicobacter pylori infection in the United States but hybrid therapy is an alternative option. Reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days, and clarithromycin plus metronidazole for the initial 7 days) is a simplified hybrid treatment. We aimed to assess the efficacies of reverse hybrid therapy vs bismuth quadruple therapy as first-line treatments for patients with H pylori infection in a randomized trial. METHODS: In a prospective study, patients with H pylori infection were randomly assigned to groups that received either reverse hybrid therapy (n = 176) or a bismuth quadruple therapy (pantoprazole, bismuth, tetracycline, and metronidazole for 14 days; n = 176). Patients were examined the end of therapy for adverse events. The study was performed from August 2015 through February 2017. The primary outcome was cure of H pylori infection, determined based on a negative result from the urea breath test, or negative results from histologic analysis, the urease test, and bacterial culture analyses. RESULTS: H pylori infection was eradicated from 96.6% of patients who received reverse hybrid therapy and 96.0% who received bismuth quadruple therapy-this difference was not significant in the intention-to-treat analysis (95% CI, 8.0% ∼ 2.2%; P = .281). There were no significant differences between therapies eradication of clarithromycin-resistant strains (88.2% with reverse hybrid therapy vs 92.3% with bismuth quadruple therapy) or metronidazole-resistant strains (100% vs 96.9%). However, reverse hybrid therapy was associated with fewer adverse events (18.7% of patients) than bismuth quadruple therapy (47.7%) (P < .001). CONCLUSIONS: In a randomized trial, we found 14-day reverse hybrid therapy to not be inferior to bismuth quadruple therapy as a first-line treatment for H pylori infection. Reverse hybrid therapy was associated with fewer adverse events. ClincialTrials.gov no: NCT02547038.

H. pylori infection and extra-gastroduodenal diseases.

Helicobacter pylori infection is the principal cause of peptic ulcer disease, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma. Recent studies have shown that it may interfere with many biological processes and determine or influence the occurrence of many diseases outside the stomach. Currently, the role of H. pylori in idiopathic thrombocytopenic purpura and iron deficiency anemia is well documented. Emerging evidence suggests that it may also contribute to vitamin B12 deficiency, insulin resistance, metabolic syndrome, diabetes mellitus and non-alcoholic liver disease. Additionally, it may increase the risk of acute coronary syndrome, cerebrovascular disease, neurodegenerative disease and other miscellaneous disorders. Different pathogenic mechanisms have been hypothesized, including the occurrence of molecular mimicry and the induction of a low-grade inflammation. This review summarizes the results of the most relevant studies on the extra-gastroduodenal manifestations of H. pylori infection.

The implementation of the consensus on the management of Helicobacter pylori and barriers to consensus.

BACKGROUND: A consensus on the management of Helicobacter pylori has been developed. We aimed to assess whether dissemination through continuing medical education (CME) could enhance the adoption of this consensus among clinicians and to explore potential barriers to acceptance. MATERIALS AND METHODS: Four CME courses were held to disseminate the consensus. Adoption surveys were performed to evaluate participants' behavior in the past and their commitment to adopt the consensus in future clinical practice after CME. The gaps and barriers to adoption were also surveyed. RESULTS: A total of 240 physicians had attended the CME courses and received surveys with the 22 statements/substatements of the consensus. Before CME, adoption was good in six, fair in ten, and poor in six. After CME, 21 statements had either an initial >90% adoption or improvement to good or fair (P < 0.001), but one still had poor even though it showed improvement (P = 0.02). Although commitment was good or fair after CME, there was a >20% gap between "commitment" and "no barrier" to adoption for 11 statements, ten of which had a main barrier of financial incentives. Among the statements with fair or poor commitment after CME, less commitment to adoption and more barriers related to financial incentives were pronounced in clinicians serving in regional/district hospitals or clinics compared to those serving in medical centers. CONCLUSIONS: Continuing medical education may improve the adoption of the H. pylori consensus. The financial incentives were shown to be a main barrier to adoption of the consensus and should be improved.

Helicobacter pylori eradication with bismuth quadruple therapy leads to dysbiosis of gut microbiota with an increased relative abundance of Proteobacteria and decreased relative abundances of Bacteroidetes and Actinobacteria.

BACKGROUND: Bismuth quadruple therapy is the treatment of choice for the first-line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the promising treatment on gut microbiota remains unclear. AIM: To investigate the short-term and long-term impacts of bismuth quadruple therapy on gut microbiota. METHODS: Adult patients with H. pylori-related gastritis were treated with 14-day bismuth quadruple therapy. Fecal samples were collected before treatment at week 2, week 8, and week 48. Nucleic acid extraction from fecal samples was performed. The V3-V4 region of the bacterial 16S rRNA gene was amplified by polymerase chain reaction and sequenced with the MiSeq followed by data analysis using Qiime pipeline. RESULTS: Eleven patients received complete follow-up. Before treatment, the most abundant phyla were Firmicutes (45.3%), Bacteroidetes (24.3%), Proteobacteria (9.9%), and Actinobacteria (5.0%). At the end of bismuth therapy, the relative abundances of Bacteroidetes and Actinobacteria decreased to 0.5% (P < .001) and 1.3% (P = .038), respectively. Additionally, the relative abundance of Verrucomicrobia also decreased from 3.2% to 1.11E-3% (P = .034). In contrast, the relative abundances of Proteobacteria and Cyanobacteria increased (P < .001 and P = .003, respectively). At week 8, the relative abundances of all phyla restored to the levels at baseline. The relative abundances of all phyla at week 48 also did not significantly differ from those at baseline. During eradication therapy, 6 patients (55%) reported at least 1 adverse event. The relative abundance of phylum Proteobacteria in patients with adverse effects was more than that in patients without adverse effects (68.7% ± 8.8% vs 43.4% ± 25.5%; P = .048). CONCLUSIONS: Bismuth quadruple therapy for H. pylori eradication can lead to short-term dysbiosis of gut microbiota. The increase in Proteobacteria in gut microbiota may attribute to the development of adverse effects during bismuth quadruple therapy.

Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment?

BACKGROUND: In patients with common bile duct stones (CBDS) and intact gallbladder, further management for the gallbladder after the CBDS clearance is still controversial. The relationship between gallbladder motility and the biliary complications were seldom discussed. Our study is to predict the subsequent biliary complications by gallbladder function test using fatty meal sonography (FMS) in patients with CBDS who had been treated by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients with an intact gallbladder and CBDS after endoscopic clearance of bile duct were enrolled. Patients received a fatty meal sonography after liver function returned to normal. The fasting volume, residual volume, and gallbladder ejection fraction (GBEF) in FMS were measured. Relationships of patients' characteristics, gallbladder function and recurrent biliary complication were analyzed. RESULTS: From 2011 to 2014, 118 patients were enrolled; 86 patients had calculus gallbladders, and 32 patients had acalculous gallbladders. After a mean follow- up of 33 months, 23 patients had recurrent biliary complications. Among 86 patients with calculus gallbladder, 15 patients had spontaneous clearance of gallbladder stones; 14 patients received cholecystectomy due to acute cholecystitis or recurrent colic pain with smooth postoperative courses. In the follow up period, six patients died of non-biliary causes. The GBEF is significant reduced in most patients with a calculus gallbladder in spite of stone color. Calculus gallbladder, alcohol drinking and more than one sessions of initial endoscopic treatment were found to be the risk factors of recurrent biliary complication. CONCLUSIONS: Gallbladder motility function was poorer in patients with a calculus gallbladder, but it cannot predict the recurrent biliary complication. Since spontaneous clearance of gallbladder stone may occur, wait and see policy of gallbladder management after endoscopic treatment of CBDS is appropriate, but regular follow- up in those patients with risk factors for recurrence is necessary.

Survey of the adherence to the consensus of gastroesophageal reflux disease before and after the implementation course.

BACKGROUND/PURPOSE: The prevalence of Gastroesophageal reflux disease (GERD) is increasing worldwide, including Asia. Although several consensus reports have been published, little is known regarding the adherence of the physicians on the consensus of GERD. We aimed to survey the agreements and adherence of physicians to the Taiwan GERD consensus before and after the continual medical education (CME) courses. METHODS: Two-hundred and twenty-seven physicians, including 81 fellows of gastroenterology, 135 qualified gastroenterologists, and 11 non-gastroenterologist attending physicians were invited to the CME course. Their agreements and adherence to the statements before and after the CME course were assessed by the pre-defined questionnaire with the aid of electronic keypads. The adherence rate before and after the CME course were compared by the McNemar test to indicate the changes in their willingness to follow the statements in clinical practice. RESULTS: The rates of agreement of the 227 participating physicians were uniformly greater than 80% for all of the 22 statements. However, the adherence rates were lower than 80% in 16 statements before the CME intervention. The adherence rates were significantly (p < 0.05) increased in 15 of these 16 statements after the CME intervention. The adherence rate can be improved to greater than 80% for those statements with high level of evidence. CONCLUSION: Although physicians agreed with the statements, the pre-CME survey disclosed limited adherence rates to the statements. The education intervention through the CME courses can improve the adherence of consensus statement, especially for those with higher level of evidence.