Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors.

BACKGROUND: The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. METHODS: Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. RESULTS: Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. CONCLUSION: In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Propranolol use in patients with cirrhosis and refractory ascites: A nationwide study.

Background: The impact of propranolol on patients with cirrhosis and refractory ascites is controversial. We conducted a nationwide longitudinal cohort study to compare the survival between patients with cirrhosis and refractory ascites, with and without using propranolol. Methods: Data of patients with cirrhosis and refractory ascites using propranolol, and controls matched by age and gender, were extracted from The National Health Insurance Research Database of Taiwan. The baseline demographic characteristics were compared between groups. Cox regression analysis was used to examine the predictors of mortality. Results: In this study, 1788 patients were enrolled in each group; 1304 patients (72.9%) in the propranolol group and 1445 patients (80.8%) in the control group died (P < 0.001). The mean survival was 34.3 ± 31.2 months in the propranolol group and 20.8 ± 26.6 months in the control group (P < 0.001). Propranolol (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.55-0.64, P < 0.001), statins (HR: 0.43, 95% CI: 0.34-0.56, P < 0.001), age (HR: 1.02, 95% CI: 1.01-1.02, P < 0.001), and diabetes mellitus (HR: 1.14, 95% CI: 1.05-1.24, P = 0.002) were the independent predictors for mortality. Conclusions: Use of propanolol was associated with reduced mortality, compared with controls, in this nationwide cohort of patients with cirrhosis and refractory ascites.

Human Papillomavirus Infection Is Associated with Decreased Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients: Taiwan Nationwide Matched Cohort Study.

Background: Hepatitis C virus (HCV) has been shown to be associated with human papillomavirus (HPV)-positive head and neck cancers. However, studies regarding HPV infection and the risk of new-onset hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients are limited. We examined the risk of HCC in CHC patients with or without HPV infection. Methods: In total, 9905 CHC patients from 2000 to 2016 constituted the whole cohort. HPV was defined as being diagnosed after HCV. The CHC cohort with HPV (N = 1981) and age-, sex-, inception point-, comorbidity-, and medication-matched non-HPV (N = 7924) were followed up until HCC, death, or 2018. HCC patients were extracted from the Taiwan Registry for Catastrophic Illness Database. We adopted the propensity score match and inverse probability of treatment weighting (IPTW) to eliminate bias. Cox proportional hazard regression analyses were performed to calculate HCC risk. Results: After a full adjustment, HPV was not associated with HCC risk (aHR, 0.74; 95% CI, 0.58−0.96 in the main model, and aHR, 0.76; 95% CI, 0.66−0.87 in IPTW, respectively). Almost all subgroup analyses verified this finding (HRs < 1.0). Conclusions: Among CHC patients older than 18 years old, those with HPV infection were associated with a lower risk of subsequent HCC.

Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B.

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) has the advantages of low price, quick onset, good efficacy, and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks, followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM-TDF groups died or received liver transplantation (P = 0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24, and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE. (This study has been registered at ClinicalTrials.gov under identifier NCT01848743).

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.

Hepatitis B Virus Screening Before Cancer Chemotherapy in Taiwan: A Nationwide Population-Based Study.

Background: Reactivation of the hepatitis B virus (HBV) during cancer chemotherapy is a severe and sometimes fatal complication. In 2009, the National Health Insurance (NHI) in Taiwan recommended and reimbursed screening for HBV infection and prophylactic antiviral therapy before cancer chemotherapy. In this study, we determined the HBV screening rate in patients with cancer undergoing chemotherapy in Taiwan. Methods: We retrospectively collected data from the National Health Insurance Research Database on patients who received systemic chemotherapy for solid or hematologic cancers from January 2000 through December 2012. We defined HBV screening based on testing for serum HBsAg within 2 years of the first chemotherapy commencement. We calculated overall and annual HBV screening rates in all patients and subgroups of age, gender, cancer type, hospital level, physician's department, and implementation of NHI reimbursement for HBV screening before cancer chemotherapy. Results: We enrolled 379,639 patients. The overall HBV screening rate was 45.9%. The screening rates were higher in males, those with hematological cancer, those at non-medical centers and medical departments. The HBV screening rates before (2000-2008) and after the implementation of NHI reimbursement (2009-2012) were 38.1 and 57.5%, respectively (p < 0.0001). The most common practice pattern of HBV screening was only HBsAg (64.6%) followed by HBsAg/HBsAb (22.1%), and HBsAg/HBcAb/HBsAb (0.7%) (p < 0.0001). The annual HBV screening rate increased from 31.5 to 66.3% (p < 0.0001). The screening rates of solid and hematological cancers significantly increased by year; however, the trend was greater in solid cancer than in hematological cancer (35.9 and 26.2%, p < 0.0001). Conclusions: The HBV screening rate before cancer chemotherapy was fair but increased over time. These figures improved after implementing a government-based strategy; however, a mandatory hospital-based strategy might improve awareness of HBV screening and starting prophylactic antiviral therapy before cancer chemotherapy.

Omeprazole vs famotidine for the prevention of gastroduodenal injury in high-risk users of low-dose aspirin: A randomized controlled trial.

BACKGROUND: Low-dose aspirin is widely used in the prevention of cardiovascular diseases. However, the use of aspirin is associated with an increased risk of gastrointestinal injury. METHODS: Low-dose aspirin users with a history of peptic ulcers who did not have gastroduodenal mucosal breaks at initial endoscopy were randomly assigned to receive famotidine (20 mg bid) or omeprazole (20 mg qd) for 6 months. Follow-up endoscopy was performed at the end of the sixth month and whenever epigastric discomfort, hematemesis, or melena occurred. The primary end point was the occurrence of gastroduodenal mucosal breaks. The secondary end points were (1) the occurrence of gastroduodenal ulcers and (2) the occurrence of gastroduodenal bleeding. RESULT: Between November 2013 and June 2018, 170 patients were randomly assigned to receive either famotidine (n = 84) or omeprazole (n = 86). The incidence of gastroduodenal mucosal breaks was 33.8% among the patients receiving famotidine, and 19.8% among those receiving omeprazole (95% CI: 0.4%-27.5%; p = 0.045). The two patient groups had comparable incidence rates of gastroduodenal ulcers (20.0% vs 9.8%; p = 0.071), and gastroduodenal bleeding (2.5% vs 0%; p = 0.243). Multivariate analysis showed that use of the proton pump inhibitor was an independent protective factor (odds ratio: 0.47; 95% CI: 0.23-0.99; p = 0.047), and that smoking was a risk factor for mucosal breaks (odds ratio: 3.84; 95% CI: 1.52-9.71; p = 0.004). CONCLUSION: Proton pump inhibitor was superior to histamine-2 receptor antagonist in the prevention of gastroduodenal mucosal breaks in high-risk users of low-dose aspirin, and smoking was an independent risk factor for developing gastroduodenal mucosal breaks.

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.

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.

Reverse hybrid therapy achieves a similar eradication rate as standard hybrid therapy for Helicobacter pylori infection.

BACKGROUND: Reverse hybrid therapy is a simplified hybrid treatment for Helicobacter pylori infection. It achieves a higher eradication rate than standard triple therapy. This study aimed to compare the efficacies of reverse hybrid and hybrid therapies in the treatment of H. pylori infection. METHODS: From September 2008 to September 2017, 490 H. pylori-infected patients who received 14 days of reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the initial 7 days; n = 252) or hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the final 7 days; n = 238) were included in this retrospective cohort study. Helicobacter pylori status was examined 6-8 weeks after therapy. RESULTS: The eradication rates of the reverse hybrid and hybrid therapies by modified intention-to-treat analysis were comparable (96.4% vs 96.6%; p = 0.899). There were no differences in the efficacy of eradication between therapies for clarithromycin-resistant strains (87.0% vs 90.0%) or metronidazole-resistant strains (97.7% vs 100.0%). In addition, there were comparable frequencies of adverse events for both treatments (18.7% vs 13.0%) and treatment adherence (94.4% vs 97.1%). CONCLUSION: Reverse hybrid therapy can achieve a similar eradication rate to hybrid therapy for H. pylori infection.

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.

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.

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.

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.

A Randomized Controlled Trial Shows that both 14-Day Hybrid and Bismuth Quadruple Therapies Cure Most Patients with Helicobacter pylori Infection in Populations with Moderate Antibiotic Resistance.

Hybrid therapy is a novel two-step treatment achieving a high eradication rate for Helicobacter pylori infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of H. pylori infection. From July 2013 to June 2015, eligible H. pylori-infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). H. pylori status was examined 6 weeks after the end of treatment. Three hundred thirty H. pylori-infected participants were randomized to receive 14-day bismuth quadruple therapy (n = 164) or 14-day hybrid therapy (n = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], -4.3% to 5.4%; P = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; P = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; P < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; P = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with H. pylori infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.).

Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial.

OBJECTIVES: Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection. METHODS: Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment. RESULTS: The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003). CONCLUSIONS: Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

Histamine-2 Receptor Antagonist Cannot Prevent Recurrent Peptic Ulcers in Patients With Atherosclerotic Diseases Who Receive Platelet ADP Receptor Antagonist Monotherapy: A Randomized-Controlled, Double-Blind, and Double-Dummy Trial.

OBJECTIVES: Proton pump inhibitor can effectively prevent recurrent peptic ulcers among atherosclerotic patients receiving clopidogrel monotherapy. However, the interaction between proton pump inhibitors and clopidogrel has raised concerns over the safety of combined use of the two medicines in clinical practice. The aims of this randomized-controlled, double-blind and double-dummy trial were to investigate the efficacy of histamine-2 receptor antagonist (H2RA) in the prevention of recurrent peptic ulcer in patients undergoing thienopyridine monotherapy. METHODS: From January 2012 to 2016, long-termed thienopyridine users with a peptic ulcer history who did not have peptic ulcers at initial endoscopy were randomly assigned to receive either famotidine (40 mg, before bedtime) or placebo (before bedtime) for 6 months. Follow-up endoscopy was performed at the end of the 6th month and whenever dyspepsia, hematemesis, or melena occurred. RESULTS: The cumulative incidence of recurrent peptic ulcer during the 6-month period was 7.0% in famotidine group (n=114) and 11.4% in the placebo group (n=114). The two patient groups had comparable cumulative incidence of peptic ulcer (difference, 4.4%; 95% confidence interval (CI), -11.7 to 2.9%; P=0.239). Additionally, there was no difference in the cumulative incidence of ulcer bleeding (2.6% vs. 1.8%; difference, 0.8%; 95% CI, -0.6 to 2.4%, P=1.000) between famotidine and placebo groups. However, the former had a lower incidence of gastroduodenal erosion than the latter (21.1% vs. 36.8%; difference, 15.7%; 95% CI, -27.3 to -4.1%; P=0.013). CONCLUSIONS: Famotidine cannot decrease the incidence of peptic ulcer or ulcer bleeding in thienopyridine users with atherosclerotic disease and a history of peptic ulcer.

Is endoscopic treatment beneficial in patients with clinically suspicious of common bile duct stones but no obvious filling defects during the ERCP examination?

BACKGROUND: Sometimes, no definite filling defect could be found by cholangiogram (ERC) during the endoscopic retrograde cholangio-pancreatiographic (ERCP) exam; even prior images had evidence of common bile duct stones (CBDS). We aimed in estimating the positive rate of extraction of CBDS who had treated by endoscopic sphincterotomy/endoscopic papillary balloon dilation (EST/EPBD) with negative ERC finding. METHODS: One hundred forty-one patients with clinically suspicious of CBDS but negative ERC, who had received EST/EPBD treatments was enrolled. Potential factors for predicting CBDS, as well as the treatment-related complications were analyzed. RESULTS: Nearly half of the patients with negative ERC, had a positive stone extraction. Only patients with high probability of CBDS were significantly associated with positive stone extraction. Moreover, patients with intermediate probability of CBDS had higher rates of overall complications, including post-ERCP pancreatitis. In addition, no significant difference of post-ERCP pancreatitis was found between EST and EPBD groups in any one group of patients with the same probability of CBDS. CONCLUSIONS: Regarding patients with negative ERC, therapeutic ERCP is beneficial and safe for patients present with high probability of CBDS. Moreover, under the same probability of CBDS, there was no significance difference in post-ERCP pancreatitis between EST and EPBD.