Once-daily rabeprazole, levofloxacin, clarithromycin-MR, and bismuth for Helicobacter pylori eradication: A randomized study of 7 or 14 days (ONCE study).

OBJECTIVE: Most therapies for Helicobacter pylori eradication utilize multiple drugs given 2-4 times daily. Patient adherence has been an impediment to reliably achieving high success. This study evaluated a once-daily dosing H pylori eradication regimen. METHODS: A prospective randomized pilot study of H pylori eradication compared once-daily treatment regimen containing levofloxacin (750 mg), clarithromycin-MR (1 g), rabeprazole (60 mg), and bismuth subsalicylate (1,048 mg) for a 7 or 14 days. CYP2C19 genotype and antibiotic susceptibility tests were performed. Successful eradication was defined as negative 13C-urea breath test at least 4 weeks after completion of treatment. RESULTS: 100 subjects were randomized (40 men, 60 women with mean age =54 years). The eradication rates were as follows: 94% (47/50; 95%CI 0.87-1.01) and 84% (42/50; 95%CI 0.73-0.95) with 14-day and 7-day therapy (OR 0.34; 95%CI 0.08-1.35, P = 0.06), respectively. Resistance rates were as follows: 13.0% for clarithromycin, 26.0% for fluoroquinolone, 2.9% for dual clarithromycin-fluoroquinolone resistance, and 62.8% for metronidazole. The 14-day regimen provided 100% eradication in patients with levofloxacin susceptible strain irrespective of the presence of clarithromycin resistance. CYP2C19 genotypes had no effect on cure rates. CONCLUSIONS: The once-daily 14-day rabeprazole-, levofloxacin-, clarithromycin-MR-, and bismuth-containing therapy provided high eradication rate suggested that triple therapies with a PPI, bismuth, and clarithromycin-MR or levofloxacin would be highly effective for once-a-day tailored therapy or as empiric therapy for first-line regimen.

Helicobacter pylori management in ASEAN: The Bangkok consensus report.

Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.

High Effective of 14-Day High-Dose PPI- Bismuth-Containing Quadruple Therapy with Probiotics Supplement for Helicobacter Pylori Eradication: A Double Blinded-Randomized Placebo-Controlled Study.

Background: Helicobacter pylori (H. pylori) infection is important risk factors for chronic gastritis, peptic ulcer and gastric cancer. Bismuth-containing quadruple therapy has recently been the first-line regimen recommended in many European countries but has limited efficacy in ASEAN especially Thailand. This study was aim to evaluate efficacy of high dose PPI Bismuth-containing quadruple therapy with probiotics supplement for H. pylori eradication. Methods: In this double-blind randomized placebo-controlled study, H. pylori infected patients were randomized to receive 7-or 14-day high dose PPI- bismuth-containing quadruple therapy with or without probiotics supplement. Probiotic was 37.5 mg Lactobacillus reuteri (Biogaia®) in tablet twice daily. CYP2C19 genotyping and antibiotic susceptibility tests were also done. H. pylori eradication was defined as a negative 13C-urea breath test at least 4 weeks after treatment. Results: 100 subjects were enrolled (72 females, 28 males, mean age=54 years). Antibiotic resistance was 15.6% for clarithromycin, 34.1% for metronidazole. CYP2C19 genotyping was performed in both group and revealed 13%, 50% and 37% for poor, intermediate and rapid metabolizers, respectively. Overall eradication rates of 7-day and 14-day regimens with probiotic were 68% and 96%; P value=0.027. The eradication rate for all patients with poor and rapid metabolizers were 100% with 14-day regimen. 14-day regimen with probiotics can provide 100% eradication with clarithromycin resistance, metronidazole resistance or dual clarithromycin and metronidazole resistance group. Furthermore, the incidence of nausea and vomiting, abdominal discomfort, and bitter taste were significantly lower in patients with probiotics group compared with placebo (6%vs.26%, P=0.002,OR=0.126,95% CI=0.03-0.53; 4%vs.18.0%, P=0.017, OR= 0.155,95% CI=0.03-0.81 and 4%vs.26%, P= 0.001,OR= 0.08, 95%CI= 0.016-0.41, respectively). Conclusions: The 14-day high dose PPI- bismuth-containing quadruple therapy with probiotic can provide an excellent cure rate for H. pylori infection as first line treatment irrespective of CYP2C19 and antibiotic resistance pattern. Adding probiotic also significantly reduced treatment-related adverse events and improve the patients' compliance.

CYP2C19 Genotype, CagA Genotype and Antibiotic Resistant Strain of Helicobacter pylori Infection

Background: H. pylori is a class I carcinogen and major cause of gastric cancer. Few previous studies reported relationship between H. pylori infection, CYP2C19 genotype and functional dyspepsia (FD) subtype. The aim of this study was to determine relationship between CYP2C19 genotype and FD subtype patients(host factor) with antibiotic resistant strains of H. pylori infection and CagA genotype(bacterial factor). Methods: FD patients who were investigated with gastroscopy at Thammasat University Hospital, Thailand during March 2017-November 2017 were enrolled. Two antral gastric biopsies were obtained for rapid urease test, E-test and cultures. CagA genotypes (CagA1a and CagA2a) were determined by PCR and CYP2C19 genotype was determined by PCR-RFLP. FD patients were categorized as epigastric pain syndrome(EPS) and postprandial distress syndrome (PDS). Results: 93 FD patients with H. pylori infection were enrolled (37 male, 56 female, mean age 54.5 years). There were 33 patients with EPS and 60 patients with PDS. CYP2C19 genotype revealed 55.9% rapid metabolizer (RM), 40.9% intermediate metabolizer (IM) and 3.2% poor metabolizer (PM) genotypes. Antibiotics susceptibility tests demonstrated 62.8% resistant to metronidazole, 12.9% resistant to clarithromycin and 27.1% resistant to fluoroquinolone. CagA 1a and CagA 2a were demonstrated in 6 patients(11.5%) and 46 patients(88.5%). CagA2a genotype was more prevalent in PDS than EPS patients (94.3%vs.76.5%; P =0.08) without significance. In intermediate metabolizer (IM), CagA2a genotype was significant higher in PDS than EPS(100% vs.25%; P=0.004). Conclusions: PDS, CYP2C19 RM genotype and CagA 2a gene of H. pylori infection were the predominant type of FD in Thailand. Metronidazole remain the most common antibiotic resistant strain of H. pylori infection in FD patients. PDS (host factor) was significantly related to CagA2a genotype (bacterial factors) only in patients with intermediate metabolizer. Appropriate dose of proton pump inhibitor (PPI) and correct regimens for H. pylori eradication in FD patients should be consider to improve clinical outcomes.

High Efficacy of Rapid Urine Test for Diagnosis of Helicobacter pylori Infection in Thai People

Background: Accurate diagnosis of Helicobacter pylori (H. pylori) infection plays an important role in further effective treatment. Rapid urine test (RAPIRUN) is a test developed for qualitative detection of urine H. Pylori antibody and use for determine the sensitivity, specificity and accuracy. However, the test needs validation in Thai population before using in clinical practice. Objective: This study aimed to compare performance of different diagnostic tests on H. pylori detection in Thai population. Methods: Total of 94 patients with dyspepsia who referred to Thammasat University Hospital, Pathumthani, Thailand, between December 2012 and April 2013 were enrolled in this study. All patients underwent gastroscopy. Then, 3 biopsies at antrum were taken for H. pylori diagnosis. including rapid urease test (Pronto Dry, Eisai, Thailand), H. pylori culture, and histopathology. Urine samples were also collected at the same time for rapid urine test (RAPIRUN H. pylori Antibody, Otsuka Pharmaceutical Co., Ltd.). Patients were diagnosed with H. pylori-positive if their culture or rapid urease tests plus histopathology yielded positive results. Results: Total of 29 patients (30.9%) were infected with H. pylori. Prevalence of H. pylori infection by rapid urease test, histopathology, culture and rapid urine test were 25.5%, 28.7%, 29.8%, and 32.9% respectively. We observed that rapid urease test, histopathology, culture, and rapid urine test had sensitivity of 82.8%, 93.1%, 93.1% and 86.2%; specificity of 100%, 100%, 100%, and 90.8%; and accuracy of 95.7%, 97.9%, 97.9%, and 89.4%, respectively. Conclusion: Rapid urine test (RAPIRUN) provided a reliable result for diagnosis of H. pylori infection. Furthermore, this rapid urine test demonstrated high accuracy, reliable, safe handle and easy to use. We suggested rapid urine test for diagnosis of H. pylori infection in Thai population since we found it less invasive and with higher reliable efficacy.

Colorectal Cancer and Precancerous Lesions Associated with Ulcerative Colitis in Thailand

Background: Ulcerative colitis(UC) is important risk factor of colorectal cancer. Many evidences from western countries confirmed this relationship but limited studies were reported in ASEAN. This study was aimed to investigate prevalence, clinical presentations, endoscopic findings, histopathology, disease progression and risk for colorectal cancer(CRC) of UC patients in Thailand. Methods: We conducted a retrospective cohort study using computer data base from Thammasat University Hospital, Pathumthani, Thailand between September 2011 and December 2015, follow-up through May 2016. Diagnosis of UC was confirmed by histopathology and whole clinical course. Results: We identified 6,082 patients who diagnosed with colitis during the study period. Of whom, only 22 patients(<1%) was confirmed of UC. Male to female ratio was 13:9 (mean age of 47.2 years). Clinical presentations were bloody diarrhea in 86.4%, watery diarrhea in 31.8% and abdominal pain in 59.1%. According to Montreal classification, disease extensions were ulcerative proctitis in 22.7%, distal UC in 50%, and pancolitis in 27.3%. Disease grading was mild in 31.8%, moderate in 9.1%, and severe in 59.1%. The prevalence of precancerous lesions were 2/22 patients(9.1%). There was no definite invasive colorectal cancer patient during study period. However, history of malnutrition was significantly higher in patients with dysplasia than those without dysplastic lesions(50%vs.0%, P-value=0.045). There was no difference in duration and disease extension between 2 groups. Interestingly, subgroup analysis demonstrated that pancolitis was significantly more common in female than male (55.6%vs.7.7%,P-value=0.02,OR=15.0, 95%CI=1.3- 169.9). Furthermore, patients' age> 35 years had significantly more severe colitis than younger group (81.25%vs.0%, P-value=0.0006) Conclusions: Although UC is rare disease in ASEAN, precancerous lesions for CRC were not uncommon. UC with pancolitis was common in female whereas severe colitis was common in elderly patients. Proper screening program and careful surveillance for precancerous lesions in patients at risk might be appropriate approach for early detection and improvement the treatment outcome.

Effectiveness of 7-Day and 14-Day Moxifloxacin-Dexlansoprazole Based Triple Therapy and Probiotic Supplement for Helicobacter Pylori Eradication in Thai Patients with Non-Ulcer Dyspepsia: A Double-Blind Randomized Placebo-Controlled Study

Background: Helicobacter pylori (H. pylori) is important cause of peptic ulcer and gastric cancer. Moxifloxacin is effective antibiotic for treatment for H. pylori. However, there were limited studies as first line therapy. Probiotics had been shown to decrease therapy-related side-effect and increase eradication rate. Aim of this study was to evaluate the efficacy of moxifloxacin-dexlansoprazole based triple therapy with probiotic for H. pylori treatment in Thailand. Methods: Patients with H. pylori infected gastritis were randomized to receive 7- or 14-day moxifloxacin-dexlansoprazole based triple therapy with probiotic or placebo. Regimen consisted of 60 mg dexlansoprazole twice daily, 400mg moxifloxacin once daily, 1g clarithromycin MR once daily. Probiotic used in this study was 282.5mg Saccharomyces boulardii (S. boulardii) in capsule prescribed twice daily. CYP2C19 genotyping, antibiotic susceptibility tests, and CagA genotyping were also done. Successful eradication was defined as a negative 13C-urea breath test at least 4 weeks after treatment. Results: Total of 108 subjects was enrolled (27 each to 7-and 14-day regimens with probiotic or placebo). Antibiotic susceptibility tests showed 29% fluoroquinolone, 19% metronidazole and 4% clarithromycin resistance. CYP2C19 genotyping demonstrated 43%, 47% and 11% were rapid, intermediate and poor metabolizers, respectively. CagA genes were positive in all patients. Eradication rates of 7-day and 14-day regimens with probiotic were 100%, and 93% respectively. There were no significant differences between eradication rate of 7-day and 14-day regimen with or without probiotics. Regarding side-effects, incidence of nausea, abdominal discomfort, bitter taste, and diarrhea were significantly lower in regimen with probiotic group compared with placebo(7.4%vs. 22.2%; p=0.028, 0.00%vs.14.8%; p=0.003, 35.2%vs.70.4%; p=0.0002, and 0.00%vs.9.3%; p=0.028, respectively). Conclusions: 7-day moxifloxacindexlansoprazole therapy plus S. boulardii provide an reliable cure rate of H. pylori in non-ulcer dyspeptic patients in Thailand, independent of CYP2C19 genotype. Probiotic adding also decreased side effects during the treatment.

Gastric Cancer and Gastrointestinal Stromal Tumors Could be Causes of non-Helicobacter Pylori non-NSAIDs Peptic Ulcers in Thailand

Background and aim: H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) remain the major causes of peptic ulcer disease. Nevertheless, non- H. pylori non-NSAIDs peptic ulcers or idiopathic peptic ulcer disease (IPUD) constitute a growing problem associated with many complications. Gastric cancer and gastrointestinal stromal tumor (GIST) have also been reported as a cause of IPUD. This study was aimed to investigate prevalence and clinical characteristics of IPUD in Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings, history of H. pylori status and NSAIDs usage were collected for patients diagnosed with PUD in Thammasat University Hospital during January 2003 ­ December 2013. Results: Total of 1,310 patients was diagnosed with PUD in our institution during the study period, of which 71 (5.4%) had a definitive diagnosis of IPUD (45 men and 26 women, mean age of 59±16.5 years). Common locations were gastric antrum (43.7%), duodenum (25.3%) and gastric body (12.7%). Common causes of IPUD were idiopathic (43.7%) and alcohol consumption (39.4%). Gastric cancer and GIST were also demonstrated in 1(1.4%) and 1(1.4%) respectively. Major complications were upper GI bleeding (73.2%) and peptic perforation (2.8%). Recurrent upper GI bleeding was detected in 23.9%. Interestingly, male patients aged<50 years with alcohol related peptic ulcer were significantly more common than female patients aged ≥ 50 years (57.8% vs 7.7%;P-value= 0.00002, OR= 16.4, 95%CI= 3.5-78 and 68.4% vs 28.9%); P-value= 0.002, OR= 5.3, 95% CI= 1.7-16.7). Conclusion: Common causes of IPUD in Thailand are idiopathic followed by alcohol consumption and steroid usage. Gastric cancer and GIST are also possible causes of IPUD. These particular ulcers had a high likelihood of developing severe complications. Appropriate screening and high level of suspicion of fatal causes eg. gastric cancer and GIST should be appropriate ways to reduce complications and improve the treatment outcome.

Low Re-infection Rate of Helicobacter pylori after Successful Eradication in Thailand: A 2 Years Study

Background: H. pylori is an important cause of chronic gastritis, peptic ulcers and gastric cancer. Re-infection rates after successful eradication vary in different regions of the world but only limited studies have been performed in ASEAN Countries to clarify this important issue. The present study was designed to evaluate the H. pylori re-infection rate and predictors of re-infection in Thailand. Methods: We recruited patients with chronic gastritis after 1 and 2 years successful H. pylori eradication from Thammasat University Hospital, Pathumthani (Central urban area) and Maesod district, Tak (Northern rural area), Thailand. 13C-UBT was performed to evaluate re-infection status after cessation of PPI, H2 blocker and antibiotics for at least 4 weeks. Statistical analysis was performed using SPSS for Windows Version 22.0 (IBM Corp., Armonk, NY). Results: A total of 105 subjects were enrolled (40 M and 65F with a mean age of 53.1 years). The overall re-infection rate was 6/105 (5.7%). The 1-year and 2-year H. pylori re-infection rates after successful eradication were only 5.1% (2/39) and 6.1% (4/66). 1-year and 2-year reinfection rates in urban areas were 2/39 (5.1%) and 1/26 (3.8%), while the 2-year reinfection rate in rural areas was 3/40 (7.5%). Location (urban vs rural area) and sex did not show any association with either 1-year or 2-year H. pylori re-infection. With 2-year reinfection, the mean age of H. pylori re-infected patients was significantly higher than those who remained cured (63.0 years vs. 51.6 years, p-value = 0.01). The annual H. pylori infection rate was 2.9%. Conclusions: 1-year and 2-year H. pylori re-infection rates after successful eradication in Thailand appear low in both rural and urban areas. H. pylori eradication for prevention of significant upper GI disease should be recommended and confirmation of successful eradication should be the aim. Patients at higher risk such as the elderly should be monitored for possible risk of H. pylori re-infection.

High Prevalence of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Thailand.

BACKGROUND: Chronic hepatitis B (CHB) infection is one of the important causes of hepatocellular carcinoma (HCC) in Thailand, involved in the pathogenesis and leading to a development of HCC with or without cirrhotic changes of the liver. This study was aimed to investigate the predictive factors for HCC among CHB patients in a tertiary care center in Thailand. MATERIALS AND METHODS: We conducted a retrospective study of CHB patients with or without HCC during the period of January 2009 and December 2014 at Thammasat University Hospital, Pathumthani, Thailand. Data on clinical characteristics, biochemical tests and radiologic findings were collected from review of medical records. RESULTS: A total of 266 patients were diagnosed with CHB in Thammasat university hospital during the study period. However, clinical information of only 164/266 CHB patients (98 males, 66 females with mean age of 49.4 years) could be completely retrieved in this study. The prevalence of HCC in CHB infection in this study was 38/164 (23.2%). CHB patients with HCC had a mean age older than those without HCC (59.5 vs 47 years, P-value = 0.01). Furthermore, history of upper GI bleeding, tattooing, blood transfusion, and chronic alcoholism were significantly more common in CHB patients with HCC than patients without HCC (13.2% vs 3.2% P-value 0.03, OR = 4.6, 95%CI = 1.2-18.1, 20% vs 3.9%, P-value = 0.01, OR= 6.1, 95% CI= 1.6-23.6, 20% vs 6.3%, P-value = 0.03, OR = 3.8, 95%CI =1.1-12.7, 62.2% vs 30.3%, P-value <0.0001, OR = 3.7, 95%CI= 1.7-8.1 respectively). Interestingly, more CHB patients with HCC had evidence of cirrhosis than those without HCC (78.9% vs 20.4%, P-value <0.0001, OR = 14.6, 95%CI = 5.8-36.7). In CHB patients with HCC, surgical therapy provided longer survival than radiofrequency ablation (RFA) (72 vs 46.5 months, P-value= 0.04). The mean survival time after HCC diagnosis was 17.2 months. CONCLUSIONS: HCC remains a major problem among patients with CHB infection in Thailand. Possible risk factors are male gender, history of upper GI bleeding, chronic alcoholism, tattooing, blood transfusion and evidence of cirrhosis. For early stage HCC patients, surgical treatment provided longer survival time than RFA. Most HCC patients presented with advanced disease and had a grave prognosis. Appropriate screening of CHB patients at risk for HCC might be an appropriate approach for early detection and improvement of long-term outcomes.