Intraluminal Therapy for Helicobacter pylori Infection-Comparison of Medicament Containing Tetracycline, Metronidazole, and Bismuth versus Amoxicillin, Metronidazole, and Clarithromycin: A Randomized Controlled Study.

Helicobacter pylori (H. pylori) can be eradicated immediately via local application of single-dose medicament on endoscopic examination. In our previous report, "the eradication rate of intraluminal therapy for H. pylori infection (ILTHPI) is 53.7% (51/95) using medicament containing amoxicillin, metronidazole, and clarithromycin". We aimed to evaluate the efficacy and adverse events of medicament containing tetracycline, metronidazole, and bismuth and to improve the efficacy of stomach acid control before ILTHPI. After usage of dexlansoprazole (60 mg b.i.d.) or vonoprazan (20 mg q.d.) for 3 days before ILTHPI, 103 of 104 (99.1%) symptomatic H. pylori-infected treatment-naïve patients achieved levels of stomach pH ≥ 6. Patients were randomized to receive ILTHPI with medicaments containing tetracycline, metronidazole, and bismuth (Group A, n = 52) or amoxicillin, metronidazole, and clarithromycin (Group B, n = 52). The eradication rate of ILTHPI was similar between Group A (76.5%; 39/51) and Group B (84.6%, 44/52) (p = 0.427) and the adverse event was mild diarrhea (2.9%; 3/104). The eradication rate significantly increased from 53.7% (51/95) to 84.6% (44/52) after acid control (p = 0.0004) for Group B patients. The overall eradication rates of successful ILTHPI plus 7-day non-bismuth (Group A) or 7-day bismuth (Group B) oral quadruple therapy for ILTHPI failure patients were both excellent (96.1% for Group A and 98.1% for Group B).

Factors Affecting the Intraluminal Therapy for Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) can be eradicated immediately while conducting an endoscopic examination. The eradication rate of intraluminal therapy for H. pylori infection (ILTHPI) is 53.7% (51/95) via local application of single-dose medicament containing amoxicillin, metronidazole, and clarithromycin. We aimed to evaluate factors affecting ILTHPI and to assess the efficacy among single antibiotics, and compared our results with combined antibiotics. We enrolled H. pylori-infected treatment-naïve symptomatic patients; 95 completed triple-antibiotic ILTHPI were evaluated for risk factors, along with 60 completed mono-antibiotic ILTHPI containing amoxicillin, clarithromycin, or metronidazole in each of the 20 patients. Univariate analysis revealed the significant influence of BMI (OR: 1.15; 95% CI: 1.03-1.27, p = 0.011) and gastric juice pH (OR: 1.35; 95% CI: 1.16-1.58, p = 0.0001). Logistic regression analysis also showed significant influence of gastric juice pH (OR: 1.30; 95% CI: 1.10-1.54, p = 0.002). The eradication rate of mono-antibiotic ILTHPI is significantly lower than triple-antibiotic ILTHPI (11.7% vs. 53.7%; p < 0.0001; α = 0.05, power = 1.0). The efficacy was 20% (4/20) for metronidazole, 10% (2/20) for amoxicillin, and 5% (1/20) for clarithromycin. In conclusion, the level of gastric juice pH is a crucial factor affecting the ILTHPI. The detection of gastric juice pH and selection of optimal intraluminal medicaments are important. Further studies with combined antibiotics for ILTHPI, perhaps metronidazole-containing medicaments, are recommended.

The Impact of Gastric Juice pH on the Intraluminal Therapy for Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori (H. pylori) can be topically eradicated in stomach lumen on endoscopic examination. The procedures of intraluminal therapy for H. pylori infection (ILTHPI) include the control of intragastric pH, mucolytic irrigation of the gastric mucosal surface, and a single-dose medicament containing antimicrobial agents. AIMS: To detect gastric juice pH and evaluate its impact on the success rate of ILTHPI. METHODS: We enrolled 324 patients with upper abdominal discomfort for endoscopic examinations. Among them, 13C-urea breath test was positive in 218 patients, where 100 underwent ILTHPI, and negative in 106. All patients had their gastric juice pH detected and set into three ranges, including normal acidity (pH < 4.0), low-level hypoacidity (pH 4.0-5.5), and high-level hypoacidity (pH ≥ 6.0). The impact of gastric juice pH on the success rate of ILTHPI was evaluated. RESULTS: Distribution of pH level showed no significant difference between two groups of H. pylori-infected patients (p = 0.942). The eradication rate of ILTHPI is significantly lower in patients with gastric juice pH below 4 (p < 0.001). CONCLUSIONS: Detection of gastric juice pH in ILTHPI is extremely important. Rapid control of stomach pH at or above 4 for patients prior to ILTHPI is strongly recommended. (NCT03124420).

Intraluminal therapy for Helicobacter pylori infection.

BACKGROUND AND AIM: Several strategies have been proposed to increase the eradication rate of Helicobacter pylori. However, the widespread increasing resistance rates to current multiple-dose oral antibiotic therapies call for alternative therapeutic approaches. We aim to develop a novel intraluminal therapy for H. pylori infection (ILTHPI). METHODS: From April 2017 to December 2017, 100 H. pylori-infected treatment-naïve patients with upper abdominal pain or discomfort underwent endoscopic examinations and concomitant ILTHPI, which comprised the control of intragastric pH, the irrigation of gastric mucosal surface with a mucolytic agent, and the application of single-dose medicaments containing antibiotic powders. The safety profiles while conducting ILTHPI and adverse events after ILTHPI were evaluated. The success of eradication was assessed based on the result of the 13 C-urea breath test 6 weeks after ILTHPI. In addition, a patient with successful ILTHPI was reconfirmed by a negative H. pylori stool antigen test four to 6 months after ILTHPI to exclude short-term recurrence. RESULTS: All the 100 enrolled patients completed the ILTHPI with good safety profiles and mild adverse events (6%). Five patients dropped out, and 51 of 95 patients (53.7%) achieved successful eradication immediately after endoscopic examinations. All 51 patients revealed negative stool H. pylori antigen tests four to 6 months after successful ILTHPI. No short-term recurrence was observed. CONCLUSIONS: We have developed a novel therapeutic approach. With the ILTHPI, H. pylori can be eradicated immediately by administrating a single-dose regimen while conducting an endoscopic examination. CLINICAL TRIALS NUMBER: NCT03124420.

Colonization of Helicobacter pylori in the gastric cardia: A comparison between the UFT300 and CLO tests.

BACKGROUND AND AIM: To assess the detection rates of Helicobacter pylori colonization in the gastric cardia with two commercial kits of rapid urease test: 5 min UFT300 and 24 h CLO test in H. pylori-infected patients. METHODS: Eighty consecutive dyspeptic patients with confirmed H. pylori infection (serology and 13C-urea breath test) were prospectively studied. During endoscopy, tissue samples using separate biopsy forceps from the cardia were taken for the UFT300 and CLO tests. The results of the UFT300 were read at 5 and 30 min, and those of the CLO test were read at 24 h. RESULTS: Of 80 enrolled patients, 17 (21.3%) and 44 (55%) had positive findings with the UFT300 at 5 and 30 min, respectively, while 72 (90%) had positive findings with the CLO test at 24 h. The CLO test is significantly more sensitive than the UFT300 in evaluating H. pylori status in the cardia. On comparing patients with and without carditis, the detection rates of the CLO test were similar (91.1% vs 88.6%; P = 0.724), and the rates of the UFT300 were also similar at 5 and 30 min. CONCLUSIONS: The rate of H. pylori colonization in the gastric cardia was 90% in H. pylori-infected patients detected with the CLO test. Although the UFT300 provides a more rapid reading of H. pylori status, the diagnostic yield of the CLO test is much higher than that of the UFT300. However, a positive result of the UFT300 may indicate a higher bacterial load in the cardia, which warrants a more effective therapeutic strategy.

Off-treatment efficacy of 3-year nucleos(t)ide analogues in chronic hepatitis B patients.

Lamivudine, telbivudine, and entecavir are the first-line drugs covered by the Taiwan National Health Insurance as 3-year treatments for patients with chronic hepatitis B virus (HBV), but the optimal treatment duration of each remains unclear. We aimed to detect HBV treatment-cessation durability, and compare the predictors in patients with and without clinical relapse. In this retrospective cohort study, 210 patients with chronic HBV who tested hepatitis B e-antigen positive or hepatitis B e-antigen negative were treated for 3 years with a nucleos(t)ide analogue. Of these, 102 patients continued therapy after 3 years, while 88 patients stopped treatment and were followed for 1 year due to financial difficulties. Efficacy was assessed in terms of alanine aminotransferase (ALT) level normalization, HBV DNA clearance, virus breakthrough, clinical relapse, and liver decompensation. The durability predictors were evaluated by host factors, HBV DNA, and drug differences. Eighty patients (14 on lamivudine, 19 on telbivudine, and 47 on entecavir) were recruited. There was no difference in clinical-relapse rate among lamivudine, telbivudine, and entecavir (35.7% vs. 36.8% vs. 31.9%, respectively; p = 0.916), and liver decompensated hepatitis was absent. In baseline clinical characteristics, there were no differences between the clinical-relapse and nonrelapse groups in age, sex, cirrhosis, prior treatment, HBV DNA, pretreatment ALT, or hepatitis B e-antigen (HBeAg). The mean 3(rd) year serum ALT level differed significantly between clinical-relapse and nonrelapse patients (37.5 U/L vs. 27.7 U/L, respectively; p = 0.044). The 3-year nucleos(t)ide analogue off-treatment in patients with chronic HBV delivered according to the Taiwan National Health Insurance guidelines had an overall 33.8% 1-year clinical-relapse rate without any decompensated hepatitis flare-ups.

Sequential therapy for 10†days versus triple therapy for 14†days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial.

OBJECTIVE: Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10 days (S10) versus triple therapy for 14 days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. DESIGN: We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS: The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. CONCLUSIONS: S10 was not superior to T14 in areas with low clarithromycin resistance. TRIAL REGISTRATION NUMBER: NCT01607918.

The Role of Liver in Determining Serum Colon-Derived Uremic Solutes.

Evidence has shown that indoxyl sulfate (IS) and p-cresyl sulfate (PCS) may be alternative predictors of clinical outcomes in chronic kidney disease (CKD). Both toxins are derived from the gastrointestinal tract and metabolised in the liver. However, it is unclear whether the liver affects the production of IS and PCS. Here, we explore the association between IS and PCS levels in liver cirrhosis and a CKD-based cohort (N = 115). Liver and kidney function was assessed and classified by a Child-Pugh score (child A-C) and a modified version of the Modification of Diet in Renal Disease (MDRD) equation (Stages 1-4), respectively. An animal model was also used to confirm the two toxin levels in a case of liver fibrosis. In patients with early liver cirrhosis (child A), IS and PCS were significantly associated with CKD stages. In contrast, serum IS and PCS did not significantly change in advanced liver cirrhosis (child C). A stepwise multiple linear regression analysis also showed that T-PCS was significantly associated with stages of liver cirrhosis after adjusting for other confounding factors (B = -2.29, p = 0.012). Moreover, the serum and urine levels of T-PCS and T-IS were significantly lower in rats with liver failure than in those without (p<0.01, p<0.05 and p<0.01, p<0.05, respectively). These results indicated that in addition to the kidneys, the liver was an essential and independent organ in determining serum IS and PCS levels. The production rate of IS and PCS was lower in patients with advanced liver cirrhosis.

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

OBJECTIVE: The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance. METHODS: The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method. RESULTS: The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance. CONCLUSIONS: The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

Large-volume endoscopic injection of epinephrine plus normal saline for peptic ulcer bleeding.

BACKGROUND AND AIM: Large-volume endoscopic injection of epinephrine has been proven to significantly reduce rates of recurrent peptic ulcer bleeding. Injection of normal saline may be equally effective for the similar hemostatic effect of local tamponade. The aim of our study was to compare the therapeutic effects of large-volume (40 mL) endoscopic injections of epinephrine, normal saline and a combination of the two in patients with active bleeding ulcers. METHOD: A total of 216 patients with actively bleeding ulcers (spurting or oozing) were randomly assigned to three groups (1:10,000 epinephrine, normal saline or diluted epinephrine plus normal saline). The hemostatic effects and clinical outcomes were compared between the three groups. RESULTS: The initial hemostatic rate was significantly lower in the normal saline group (P < 0.05). The volume of injected solution required for the arrest of bleeding was significantly larger in the normal saline group (P < 0.01). Mean duration for arrest of bleeding was significantly longer in the normal saline group (P < 0.01). There were no significant differences between the three groups with respect to the rates of recurrent bleeding, surgical intervention, 30-day mortality, amount of transfusion and duration of hospitalization. Significant elevation of systolic blood pressure (P < 0.05) and persistent high pulse rate after endoscopic injection were observed in the epinephrine group. CONCLUSIONS: For patients with active bleeding ulcers (spurting or oozing), we recommend a large-volume (40 mL) combination injection using diluted epinephrine to cease bleeding, followed by injection of normal saline to achieve sustained hemostasis.

Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleeding.

AIM: To define the optimal injection volume of epinephrine with high efficacy for hemostasis and low complication rate in patients with actively bleeding ulcers. METHODS: This prospective, randomized, comparative trial was conducted in a medical center. A total of 228 patients with actively bleeding ulcers (spurting or oozing) were randomly assigned to three groups with 20, 30 and 40 mL endoscopic injections of an 1:10000 solution of epinephrine. The hemostatic effects and clinical outcomes were compared between the three groups. RESULTS: There were no significant differences in all background variables between the three groups. Initial hemostasis was achieved in 97.4%, 98.7% and 100% of patients respectively in the 20, 30 and 40 mL epinephrine groups. There were no significant differences in the rate of initial hemostasis between the three groups. The rate of peptic ulcer perforation was significantly higher in the 40 mL epinephrine group than in the 20 and 30 mL epinephrine groups (P < 0.05). The rate of recurrent bleeding was significantly higher in the 20 mL epinephrine group (20.3%) than in the 30 (5.3%) and 40 mL (2.8%) epinephrine groups (P < 0.01). There were no significant differences in the rates of surgical intervention, the amount of transfusion requirements, the days of hospitalization, the deaths from bleeding and 30 d mortality between the three groups. The number of patients who developed epigastric pain due to endoscopic injection, was significantly higher in the 40 mL epinephrine group (51/76) than in the 20 (2/76) and 30 mL (5/76) epinephrine groups (P < 0.001). Significant elevation of systolic blood pressure after endoscopic injection was observed in the 40 mL epinephrine group (P < 0.01). Significant decreasing and normalization of pulse rates after endoscopic injections were observed in the 20 mL and 30 mL epinephrine groups (P < 0.01). CONCLUSION: Injection of 30 mL diluted epinephrine (1:10000) can effectively prevent recurrent bleeding with a low rate of complications. The optimal injection volume of epinephrine for endoscopic treatment of an actively bleeding ulcer (spurting or oozing) is 30 mL.

Clinical features of human intestinal capillariasis in Taiwan.

Human intestinal capillariasis is a rare parasitosis that was first recognized in the Philippines in the 1960 s. Parasitosis is a life threatening disease and has been reported from Thailand, Japan, South of Taiwan (Kaoh-Siung), Korea, Iran, Egypt, Italy and Spain. Its clinical symptoms are characterized by chronic diarrhea, abdominal pain, borborygmus, marked weight loss, protein and electrolyte loss and cachexia. Capillariasis may be fatal if early treatment is not given. We reported 14 cases living in rural areas of Taiwan. Three cases had histories of travelling to Thailand. They might have been infected in Thailand while stayed there. Two cases had the diet of raw freshwater fish before. Three cases received emergency laparotomy due to peritonitis and two cases were found of enteritis cystica profunda. According to the route of transmission, freshwater and brackish-water fish may act as the intermediate host of the parasite. The most simple and convenient method of diagnosing capillariasis is stool examination. Two cases were diagnosed by histology. Mebendazole or albendezole 200 mg orally twice a day for 20-30 d is the treatment of choice. All the patients were cured, and relapses were not observed within 12 mo.