The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is ...generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori.
We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes.
In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval CI, 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence.
HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.
Study Objective. To determine the factors that may influence Helicobacter pylori eradication in patients receiving omeprazole‐amoxicillin dual therapy.
Design. Prospective, randomized study.
Setting. ...University‐affiliated hospital in Taiwan.
Patients. A total of 128 adults (age range 20–75 yrs) with H. pylori‐positive duodenal ulcer were enrolled; 121 completed the final evaluation.
Intervention. Patients were randomly assigned to one of four omeprazole‐amoxicillin treatment groups, with each treatment administered for 2 weeks: O2A2 group (33 patients)—omeprazole 20 mg twice/day plus amoxicillin 500 mg 4 times/day; O2A1 group (32 patients)—omeprazole 20 mg twice/day plus amoxicillin 250 mg 4 times/day; O1A2 group (32 patients)—omeprazole 20 mg once/day plus amoxicillin 500 mg 4 times/day; and O1A1 group (31 patients)—omeprazole 20 mg once/day plus amoxicillin 250 mg 4 times/day
Measurements and Main Results. Data were collected on H. pylori status, histologic parameters, antibiotic resistance, intragastric pH, cytochrome P450 (CYP) 2C19 genotype, and adverse reactions. The intent‐to‐treat cure rates (95% confidence interval CI) in groups O2A2, O2A1, O1A2, and O1A1 were 76% (95% CI 59–87%), 72% (95% CI 54–84%), 50% (95% CI 34–66%) and 52% (95% CI 35–68%), respectively. Eradication of H pylori infection was statistically significantly dependent on omeprazole dosage, CYP2C19 genotype, age, gastritis status, and H. pylori density. All CYP2C19 poor metabolizers were cured, whereas the H pylori cure rate in CYP2C19 extensive metabolizers varied from 44–76% in the different treatment groups. Eradication of H. pylori was favored in the omeprazole higher dose groups versus the lower dose groups (79% vs 53%, p=0.004). No secondary antibiotic resistance was found. Thirty‐seven (95%) of 39 patients who failed with the initial treatment were cured by subsequent antibiotic susceptibility‐driven proton pump inhibitor‐based triple therapy.
Conclusion. Provided a maintenance dose of amoxicillin is given every 6 hours, eradication of H pylori infection was significantly dependent on omeprazole dosage, CYP2C19 genotype, age, gastritis status, and H pylori density.
The increasing emergence of Helicobacter pylori strains resistant to antibiotics may cause unsuccessful treatment. An alternative agent or mixture with anti-H. pylori effect is urgently required to ...reduce H. pylori infection. We explored the preventive and therapeutic potential of a combination of catechins and sialic acid on H. pylori-infected human gastric cells in vitro and in mice in vivo. We evaluated the anti-H. pylori activity of catechins and/or sialic acid using the agar dilution and checkerboard methods. The effect of catechins and/or sialic acid on H. pylori infection-induced oxidative stress and apoptosis/autophagy in cell culture was explored using an ultrasensitive chemiluminescence analyzer, immunocytochemistry, and Western blotting. Specific pathogen-free BALB/c mice were divided into uninfected control, infected control, pretreated, and post-treated groups. The effects of catechins/sialic acid were determined by histology and immunocytochemistry. The combination of catechins and sialic acid showed synergistic or additive anti-H. pylori activity and significantly reduced inducible nitric oxide synthase expression and Bax/Bcl-2-mediated apoptosis but enhanced Beclin-1-mediated autophagy. All mice infected with H. pylori displayed gastritis and accumulation of 3-nitrotyrosine and 4-hydroxynonenal. Pretreatment with catechins/sialic acid completely prevented H. pylori infection and resulted in normal histology. Post-treatment with catechins/sialic acid decreased the bacterial load and gastritis score and eradicated up to 60% of H. pylori infections in a dose-dependent manner. This is the first demonstration to our knowledge of a nonprobiotic, nonantibiotic treatment that is 100% effective in preventing and has promising possibilities for treating H. pylori infection. Further studies are needed to confirm this result in humans.
The inflammasome/caspase-1 signaling pathway in immune cells plays a critical role in bacterial pathogenesis; however, the regulation of this pathway in the gastric epithelium during Helicobacter ...pylori infection is yet to be elucidated. Here, we investigated the effect of catechins (CAs), sialic acid (SA), or combination of CA and SA (CASA) on H. pylori-induced caspase-1-mediated epithelial damage, as well as H. pylori colonization in vitro (AGS cells) and in vivo (BALB/c mice). Our results indicate that the activity of caspase-1 and the expression of its downstream substrate IL-1β were upregulated in H. pylori-infected AGS cells. In addition, we observed increased oxidative stress, NADPH oxidase gp91phox, CD68, caspase-1/IL-1β, and apoptosis, but decreased autophagy, in the gastric mucosa of H. pylori-infected mice. We have further demonstrated that treatment with CASA led to synergistic anti-H. pylori activity and was more effective than treatment with CA or SA alone. In particular, treatment with CASA for 10 days eradicated H. pylori infection in up to 95% of H. pylori-infected mice. Taken together, we suggest that the pathogenesis of H. pylori involves a gastric epithelial inflammasome/caspase-1 signaling pathway, and our results show that CASA was able to attenuate this pathway and effectively eradicate H. pylori infection.
BACKGROUND : By NAT, HBV DNA is occasionally detectable in blood donors with past HBV infection but negative for HBsAg. Whether or not these donors can cause transfusion‐transmitted HBV infections is ...uncertain.
STUDY DESIGN AND METHODS : To determine whether or not donors with past HBV infection but negative for HbsAg can cause HBV transfusion‐transmitted infections, recipients followed for blood transfusion in a university medical center in Taiwan were studied. HBV DNA and serologic markers were tested in donors and recipients.
RESULTS : Of 1038 enrolled recipients, 910 completed the 6‐month post‐transfusion follow‐up visit. Of these, only 39 patients (4.3%) tested negative on the pretransfusion sample for HBsAg, anti‐HBs, anti‐HBc, and HBV DNA by PCR. These 39 HBV‐naive recipients had been transfused with blood from 147 donations for which stored samples were available for HBV DNA testing by PCR; 11 of these HBsAg‐negative samples tested positive for HBV DNA and anti‐HBc. Two of the 11 patients who received the HBV‐DNA‐positive donations (18%) became positive for HBV DNA, and one seroconverted to anti‐HBc and finally to anti‐HBs, with a mild transient elevation of serum ALT activities. Based on the one confirmed case of HBV transmission, a projection was made that approximately 200 post‐transfusion HBV infections could occur in one million units of transfused blood in Taiwan.
CONCLUSIONS : In HBV‐endemic areas like Taiwan, where blood donors are screened for HBsAg only, the risk of transfusion‐transmitted HBV appears to be substantial. Implementation of NAT for blood screening in these settings warrants consideration.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Asians have a higher percentage of CYP2C19 poor metabolizers (PMs) and a high percentage of Helicobacter pylori infection compared with Whites.
• Although ...rabeprazole has been suggested to be least affected by CYP2C19 genotype, the pharmacokinetic properties of rabeprazole have been shown to correlate with the CYP2C19 genotype.
• Short‐term (i.e. <7 days) rabeprazole‐based triple therapy has been suggested for its use in eradicating H. pylori, whereas the eradication rate has been reported variously as 90–27% without CYP2C19 genotyping.
WHAT THIS STUDY ADDS
• Population pharmacokinetic–pharmacodynamic analysis showed that the plasma rabeprazole levels, the values of keo (the first‐order rate constant for drug dissipation from the effect compartment), and the predicted gastrin‐time profile were higher in CYP2C19 PMs than in extensive metabolizers (EMs) after multiple dosing.
• Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain, whereas the eradication rates ranged from 58 to 85% in CYP2C19 EMs.
AIMS The aim was to explore the role of CYP2C19 polymorphism in short‐term rabeprazole‐based triple therapy against Helicobacter pylori infection.
METHODS Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1–4, days 4–7, or days 1–7. A direct link model with an effect compartment was used in the population pharmacokinetic–pharmacodynamic analysis. The status of H. pylori infection was evaluated.
RESULTS Rabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7 vs. 16.8 l h−1 in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC50 and keo of gastrin response increased with multiple doses of rabeprazole. The keo values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 × 10−4 l min−1), and higher than in EMs on day 4 (0.804 vs. 0.169 × 10−4 l min−1) of rabeprazole treatment. The predicted gastrin‐time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7. Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%.
CONCLUSIONS CYP2C19 genotypes play a role in H. pylori eradication therapy. Rabeprazole‐based short‐term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication.
Background/Aims: To evaluate ultrasound-guided cutting biopsy for hepatocellular carcinoma, we report findings from 10 years of experience.
Methods: We performed 455 ultrasound-guided cutting ...biopsies of hepatic tumors in 420 patients with hepatocellular carcinoma from 1981 to 1990.
Results: Liver tissues were adequately sampled for a histological diagnosis of hepatocellular carcinoma in the initial biopsy in 391 sessions. The remaining 64 were proved to have hepatocellular carcinoma after subsequent studies. Ultrasound-guided biopsy changed the initial diagnosis in 9 of the 420 patients: three had been diagnosed with liver abscess, and six with metastatic liver tumors. Complications of the biopsy were rare: the tumor had spread to the chest wall in nine, and internal bleeding was noted in five patients. There was no mortality and no other sequelae.
Conclusions: Ultrasound-guided biopsy of hepatic tumors is important in the diagnosis of liver cancer, but this technique should be applied only when the image diagnosis and results of fine needle biopsy are equivocal to minimize possible complications. For patients with small HCCs, who are candidates for surgical resection of hepatocellular carcinoma or liver transplantation, it should not be considered as a first-step invasive procedure.
Objective: Gastroesophageal flap valve (GEFV) grade predicts severe gastroesophageal reflux disease in Caucasians, but its role in other populations is unclear. This study evaluated the significance ...of endoscopic grading of the GEFV in Taiwanese subjects.
Methods: Five hundred and six consecutive patients undergoing routine check‐ups at the National Taiwan University Hospital were enrolled. Symptoms of upper gastrointestinal disease and endoscopic severity of esophageal mucosal injury were correlated to GEFV grades according to the Hill classification.
Results: The frequency of abnormal valves (Hill grades III or IV) was 27.3%. Of these, 42.7% had erosive esophagitis (EE). The majority of patients with EE were classified as Los Angeles grades A and B (79.7 and 16.9%, respectively). The prevalence of EE, hiatal hernia and, to a lesser degree, non‐erosive reflux disease, increased with altered GEFV. Patients with abnormal valves were younger and more likely to be male, overweight, and to have atypical and extraesophageal symptoms.
Conclusions: Taiwanese patients with abnormal GEFVs share similar characteristics and risk factors with the patients who have EE. Endoscopic grading of the GEFV is highly associated with GERD, and in particular EE, in subjects undergoing routine endoscopy.
Study Objectives. To determine the pharmacokinetic and pharmacodynamic rationale for the optimum regimen of rabeprazole in the treatment of Helicobacter pylori infection in patients who are ...cytochrome P450 (CYP) 2C19 poor metabolizers or extensive metabolizers.
Design. Prospective, multiple‐dose pharmacokinetic and pharmacodynamic study.
Setting. University‐affiliated medical center in Taiwan.
Subjects. Twelve healthy volunteers (aged 20–30 yrs) who were identified as CYP2C19 poor metabolizers (six subjects) or extensive metabolizers (six).
Intervention. Each subject received rabeprazole 20 mg twice/day for 3 consecutive days and once/day on the fourth day.
Measurements and Main Results. Pharmacokinetic and pharmacodynamic parameters were compared between CYP2C19 poor and extensive metabolizers on day 1 and day 4 of dosing. The mean ± SD values of area under the concentration‐time curve of rabeprazole and rabeprazole thioether were significantly higher in poor metabolizers than in extensive metabolizers on day 1 (5357 ± 883 vs 1131 ± 512 ng·hr/ml and 1703 ± 432 vs 561 ± 358 ng·hr/ml, respectively; p<0.001) and on day 4 (5601 ± 669 vs 1619 ± 778 ng'hr/ml and 1914 ± 378 vs 511 ± 360 ng·hr/ml, respectively; p<0.001). However, no significant difference was noted between day 1 and day 4 of dosing within the same genotype groups. Only CYP2C19 poor metabolizers had significantly higher plasma gastrin levels on day 4 compared with those levels on day 1 (p<0.05). The pharmacokinetic‐pharmacodynamic relationship of rabeprazole appears to be time dependent.
Conclusion. The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.
A different spectrum of genetic changes including p53, c-erbB-2, c-met, adenomatous polyposis coli (APC), and deleted in colorectal cancer (DCC) is involved in gastric cancer (GC). The aim of this ...study was to correlate these alterations with histological subtypes, tumor stages, and Helicobacter pylori infection.
Specimens of 163 patients with GC were immunostained for p53, c-erbB-2, and c-met, and polymerase chain reaction was performed in them to determine loss of heterozygosity (LOH) of APC and DCC.
Overexpression of p53 was more frequent in early intestinal than early diffuse GC and was noted in the stage progression of diffuse but not intestinal GC. Overexpression of c-erbB-2 occurred more commonly in intestinal GC and advanced GC of both types. Overexpression of c-met was greater in diffuse GC, particularly at advanced stage. LOH of APC was more common in intestinal GC irrespective of the stage but rarely in diffuse GC. LOH of DCC occurred primarily in advanced intestinal GC and infrequently in early GC or advanced diffuse GC. Alterations of these five genes were not correlated with H. pylori infection.
A distinct genetic pathway exists in gastric carcinogenesis of different histological subtypes and their tumor progression, in which H. pylori infection may play an equal role or no role.
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