In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4–86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, ...amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7–88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6–92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters.
This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879.
Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 33% per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p<0·0001), and BQ10 (p<0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p<0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% 15/127 to 66% 38/58 for T14, 7% 10/135 to 64% 28/44 for C10), cefazolin (13% 16/127 to 43% 25/58 for T14, 10% 13/135 to 41% 18/44 for C10), cefmetazole (8% 10/127 to 26% 15/58 for T14, 4% 5/135 to 18% 8/44 for C10), levofloxacin (8% 10/127 to 35% 20/58 for T14, 7% 10/135 to 32% 14/44 for C10), gentamicin (13% 19/146 to 47% 27/58 for T14, 15% 22/149 to 45% 20/44 for C10), and trimethoprim–sulfamethoxazole (33% 48/146 to 86% 50/58 for T14, 28% 42/148 to 86% 38/44 for C10; p<0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10.
Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy.
National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
2.
Right upper quadrant abdominal pain with fever Lin, I‐Tsung; Bair, Ming‐Jong
Journal of the American College of Emergency Physicians Open,
December 2023, Volume:
4, Issue:
6
Journal Article
Peer reviewed
Open access
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background & Aims
Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long‐term entecavir therapy in ...reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB‐related cirrhosis patients.
Methods
The C‐TEAM (Cirrhosis‐Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment‐naïve patients with CHB‐related cirrhosis and baseline HBV‐DNA≥2000 IU/mL receiving long‐term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort.
Results
In total, 1315 entecavir‐treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow‐up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28‐0.57. Additionally, an older age, the male gender, HBeAg positivity, alpha‐fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver‐related and all‐cause mortality. These findings were confirmed by propensity score‐matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1‐year virological response were predictive of HCC development.
Conclusions
Four‐year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB‐related cirrhosis.
See Editorial on Page 1752
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Summary Background Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly ...understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. Methods In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive13 C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01906879. Findings Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 95% CI 87·6–92·6) for 10-day bismuth quadruple therapy, 85·9% (464/540 82·7–88·6) for 10-day concomitant therapy, and 83·7% (452/540 80·4–86·6) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% 95% CI 2·7–10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. Interpretation Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. Funding National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Understanding the prescribing patterns could better inform irritable bowel syndrome (IBS) management and health policy. However, there is no study on prescribing patterns of IBS in Taiwan. This study ...was conducted to evaluate the epidemiology, clinical features, and prescribing patterns of IBS in Taiwan.
This population-based cross-sectional study was performed by retrieving claim data from National Health Insurance Research Database (NHIRD) between 2011 and 2018 in Taiwan. Patients who were diagnosed with IBS during 2012-2018 and more than 20 years old were included. The annual incidence and prevalence of IBS were estimated. The characteristics and prescribing pattern were evaluated among IBS population. The population with IBS were followed from index date until 1 year after or death.
A total of 1691596 patients diagnosed with IBS were identified from 2012 to 2018. The average annual incidence and prevalence of IBS in Taiwan were calculated as 106.54 and 181.75 per 10,000 population. The incidence and prevalence showed a decreasing trend from 2012 to 2018. Hypertension, dyslipidemia, chronic liver disease, peptic ulcer, gastroesophageal reflux disease (GERD), anxiety, and sleep disorder were the prevalent comorbidities in IBS population. At 1 year after IBS diagnosis, the rates of peptic ulcer and GERD; the utilizations of abdominal ultrasonography, upper gastrointestinal (GI) endoscopy, and lower GI endoscopy; the prescribing rate of propulsives, simethicone, antacids, H2-blockers, and proton pump inhibitors significantly increased. Approximately 70% of participants received IBS-related treatment. Antispasmodics was the most frequently prescribed medication class, followed by laxatives and antidiarrheals. Only 48.58% of patients made return visit for IBS at 1 year after IBS diagnosis. Consequently, the proportion of consultation for IBS and the prescribing rates of all medications were decreased considerably after IBS diagnosis.
The incidence and prevalence of IBS showed a decreasing trend from 2012 to 2018. More than two-third of patients received treatment for IBS. Antispasmodics was widely used for IBS management. However, patients may have a short symptom duration or receive a short course of IBS-related treatment in Taiwan. These findings provided the whole picture of the epidemiology and prescribing pattern of the IBS population in Taiwan.
Antiviral therapy for patients with non-cirrhotic chronic hepatitis B and minimally raised alanine aminotransferase (ALT) is controversial. We aimed to investigate the efficacy and safety of ...tenofovir disoproxil fumarate in reducing the risk of disease progression in this patient population.
TORCH-B is a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial done at six teaching hospitals in Taiwan that enrolled patients with chronic hepatitis B. Eligible patients were aged 25–70 years and had substantial viraemia (viral DNA >2000 IU/mL) and minimally raised serum ALT concentrations more than one-fold but less than two-fold the upper limit of normal (ULN). Exclusion criteria included liver cirrhosis and previous antiviral treatment. Eligible participants were randomly assigned (1:1), stratified by site with a fixed block size of ten, to receive either 300 mg of oral tenofovir disoproxil fumarate or placebo once daily for 3 years. The participants, investigators, research coordinators, pathologists, laboratory personnel, and staff involved in patient care or assessment were masked to treatment assignment. 0·5 mg/day of oral entecavir was added to rescue acute hepatitis flare. The coprimary outcomes were change in necroinflammation severity on the Knodell scale and change in fibrosis stage on the Ishak scale and were evaluated in the modified intention-to-treat population, which comprised all patients with paired liver biopsies. Safety was evaluated in all patients who were randomly assigned. This trial is registered at ClinicalTrials.gov, NCT01522625, and is completed.
From Jan 30, 2012, to Nov 10, 2015, 875 patients were screened and 160 were randomly assigned to receive either tenofovir disoproxil fumarate (n=79) or placebo (n=81). The coprimary outcomes were assessed in 146 patients (73 in each group). Liver fibrosis progressed (an increase of ≥1 stage) in 19 (26%, 95% CI 17–38) of 73 patients in the tenofovir disoproxil fumarate group and in 34 (47%, 35–59) of 73 patients in the placebo group (relative risk RR 0·56, 95% CI 0·35–0·88; p=0·013), whereas necroinflammation progressed (an increase of ≥2 points) in five (7%, 95% CI 2–15) patients in the tenofovir disoproxil fumarate group and in 12 (16%, 9–27) patients in the placebo group (RR 0·42, 95% CI 0·15–1·12; p=0·084). Two (3%) of 79 patients in the tenofovir disoproxil fumarate group and 13 (16%) of 81 patients in the placebo group had acute hepatitis flare requiring add-on entecavir (RR 0·16, 95% CI 0·04–0·68; p=0·013). The two groups were otherwise similar in occurrences of adverse events. No patients died.
Tenofovir disoproxil fumarate reduces the risk of progression in liver fibrosis in patients with chronic hepatitis B and minimally raised ALT, but its effect on necroinflammation is non-significant.
The Taiwan Ministry of Science and Technology, E-Da Hospital, the Taipei Institute of Pathology, Gilead Sciences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and Aim
Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux ...disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms.
Methods
This study enrolled 303 consecutive patients with proton pump inhibitor treatment‐naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non‐dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances.
Results
There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms.
Conclusions
Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tenofovir and entecavir demonstrated substantial effectiveness in the reversion of fibrosis and reversed cirrhosis in patients with hepatitis B virus (HBV)-related cirrhosis. However, there has not ...been a definitive conclusion regarding the association between entecavir and tenofovir on the risk of cirrhosis-related complications. Therefore, this study aimed to investigate the comparative effectiveness between tenofovir and entecavir in HBV-related cirrhosis patients.
This was a retrospective study using Taiwan's Health Insurance Research Database. We enrolled newly diagnosed HBV-related cirrhosis patients who initiated entecavir and tenofovir between 2011 and 2019. Treatment groups were determined by the initial HBV antiviral medication prescribed. The primary composite outcome was the development of hepatocellular carcinoma (HCC), death from any causes, and liver transplantation. The secondary outcomes included all the individual components of the primary outcome. The incidence rate was calculated for each outcome for both treatment groups using the Fine-Gray subdistribution hazard models. Propensity score adjustment was used to balance treatment groups.
A total of 7,316 propensity score-matched treatment-naïve patients and 3,524 propensity score-matched treatment-experienced patients were included. Within treatment-naïve patients, those receiving tenofovir showed significantly lower hazards of developing the composite outcome (HR, 0.79;
< 0.0001), hepatocellular carcinoma (HR, 0.86;
= 0.027), mortality (HR, 0.75;
< 0.0001), and liver transplantation (HR, 0.70;
= 0.0189) than those receiving entecavir. As for treatment-experienced patients, tenofovir was associated with a significantly lower risk of the composite outcome (HR, 0.82;
= 0.0033) and hepatocellular carcinoma (HR, 0.60;
< 0.0001), but it did not show a significantly different risk of all-cause mortality (HR, 0.93;
= 0.3374) or liver transplantation (HR, 1.17;
= 0.5112) compared to entecavir.
Tenofovir presented a significantly lower incidence of cirrhosis-related complications than entecavir in patients with hepatitis B virus-related cirrhosis. However, no statistically significant difference in death and liver transplantation was seen in treatment-experienced patients.
Background
We aimed to assess the latest prevalence and secular trend of Helicobacter pylori infection and its association with the incidence and mortality of gastric cancer in Taiwan.
Materials and ...Methods
Adults naive to H. pylori eradication received 13C‐urea breath test (13C‐UBT), H. pylori stool antigen test, and serology test during 2019–2020 in this prospective screening program. Children and adolescent aged between 7 and 19 years received 13C‐UBT for H. pylori screening. We also conducted a systematic review and meta‐analysis to assess the secular trend of prevalence of H. pylori from 1990 to 2020 in Taiwan. The secular trends of age‐standardized incidence and mortality of gastric cancer were obtained from the Taiwan Cancer Registry.
Results
A total of 1494 participants were enrolled, including 294 children or adolescents and 1200 adults. The overall prevalence of active H. pylori infection by 13C‐UBT was 26.6% (397/1494), which was 30.8% in adults and 9.5% in adolescents/children. The age‐standardized prevalence of active H. pylori infection was 32.3% in adults after adjustment of the population structure in Taiwan. Of the 29 studies including 38,597 subjects eligible for the meta‐analysis, the pooled prevalence of H. pylori infection decreased from 63.8% (95% CI: 55.9%–71%) in 1990–2000 to 28.2% (95% CI:21.8%–35.6%) in 2016–2020. The age‐standardized incidence and mortality of gastric cancer have also declined from 15.2 to 10.75 per 100,000, respectively, in 1999 to 9.29 and 5.4 per 100,000, respectively, in 2019.
Conclusions
The prevalence of H. pylori infection has declined in Taiwan, which correlates with the declining trends of age‐standardized incidence and mortality of gastric cancer in Taiwan.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Lifestyle modification is the standard of care for nonalcoholic fatty liver disease (NAFLD) patients. We aimed to investigate the efficacy of a short‐term lifestyle modification program in the ...disease course of Taiwanese nonalcoholic steatohepatitis (NASH) patients with paired biopsies. All patients received a 6‐month, strict multidisciplinary program of lifestyle modifications led by physicians, dieticians, and nursing staff. The histopathological and clinical features were assessed. The endpoints were normalization of transaminase levels, metabolic parameters, a decrease in the NAFLD activity score (NAS) ≥1, and a decrease in the fibrosis stage ≥1. We also aimed to elucidate the predictors associated with disease progression. A total of 37 patients with biopsy‐proven NASH were enrolled. The normalization of transaminase levels increased from 0% to 13.5%. There were also significantly increased proportions of patients with normal total cholesterol, triglyceride, and hemoglobin A1c levels. Fifteen (40.5%) patients had an increased NAS ≥1, whereas 10 (27.0%) patients had NAS regression. Twelve (32.4%) patients had increased fibrosis ≥1 stage. Only 2 (5.4%) patients experienced fibrosis regression. A high fasting plasma glucose (FPG) level was associated with NAS progression. Older age and higher transaminase and FPG levels were factors associated with fibrosis progression. Seven (18.9%) patients achieved a body weight reduction >3%, and 4 (57.1%) of them experienced NAS regression. No significant effect of weight reduction on the progression of fibrosis was observed. The short‐term lifestyle modification program significantly decreased liver enzymes and metabolic parameters in NASH patients. A more precise or intensive program may be needed for fibrosis improvement.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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