Yao-Chun Hsu

Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial

BACKGROUND Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. METHODS For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. FINDINGS Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4-94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2-90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0-86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 [95% CI 7·2-34·5]; p=0·003) and PP analyses (13·7 [8·3-40], p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. INTERPRETATION Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. FUNDING National Taiwan University Hospital and National Science Council.

Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients

Hepatitis C virus (HCV) infection is causally associated with insulin resistance and diabetes mellitus. This population‐based cohort study aimed to investigate whether antiviral therapy for HCV infection was associated with improved clinical outcomes related to diabetes. From the Taiwan National Health Insurance Research Database, 2,267,270 Taiwanese residents diagnosed with diabetes mellitus were screened for eligibility. HCV infection was defined by a specific diagnosis code and measurement of serum antibody. After excluding patients with serious comorbidity, we enrolled a total of 1,411 eligible patients who received pegylated interferon plus ribavirin (treated cohort), and matched them 1:1 with 1,411 untreated controls by propensity scores (untreated cohort). We also matched the treated cohort 1:4 with 5,644 diabetic patients without HCV infection (uninfected cohort). Participants were followed up for the occurrence of endstage renal disease (ESRD), ischemic stroke, and acute coronary syndrome (ACS) after receiving antiviral treatment or the corresponding calendar date. From 2003 to 2011, the 8‐year cumulative incidences of ESRD in the treated, untreated, and uninfected cohorts were 1.1% (95% confidence interval [CI], 0.3‐2.0%), 9.3% (95% CI, 5.9‐12.7%), and 3.3% (95% CI, 2.3‐4.3%), respectively (P < 0.001); those of stroke were 3.1% (95% CI, 1.1‐5.0%), 5.3% (95% CI, 3.0‐7.5%), and 6.1% (95% CI, 4.8‐7.4%), respectively (P = 0.01); and those for ACS were 4.1% (95% CI, 2.1‐6.1%), 6.6% (95% CI, 3.7‐9.5%), and 7.4% (95% CI, 5.9‐9.0%), respectively (P = 0.05). As compared with the untreated cohort, antiviral treatment was associated with multivariate‐adjusted hazard ratios of 0.16 (95% CI, 0.07‐0.33%) for ESRD, 0.53 (95% CI, 0.30‐0.93) for ischemic stroke, and 0.64 (95% CI, 0.39‐1.06) for ACS. Conclusion: Antiviral treatment for HCV infection is associated with improved renal and cardiovascular outcomes in diabetic patients. (Hepatology 2014;59:1293‐1302)

Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection

Objective To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV. Methods This nationwide cohort study screened 293 480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12 384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24 768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute coronary syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were calculated after adjustment for competing mortality. Results The treated and untreated cohorts were followed up for a mean (±SD) duration of 3.3 (±2.5) and 3.2 (±2.4) years, respectively, until 31 December 2011. The calculated 8-year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune catastrophes between treated and untreated patients were 0.15% vs 1.32% (p<0.001), 2.21% vs 2.96% (p=0.027), 1.31% vs 1.76% (p=0.001) and 0.57% vs 0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07 to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune catastrophes. These favourable associations were invalid in incompletely treated patients with duration <16 weeks. Conclusions Antiviral treatment for HCV is associated with improved renal and circulatory outcomes, but unrelated to catastrophic autoimmune diseases.

Postoperative peg‐interferon plus ribavirin is associated with reduced recurrence of hepatitis C virus‐related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) frequently recurs after surgical resection. This population‐based research aimed to investigate the association between postoperative antiviral treatment and risk of recurrent HCC in patients with hepatitis C virus (HCV) infection. By analyzing the Taiwan National Health Insurance Research Database, we initially screened a total of 100,938 patients diagnosed with HCC for the first time between October 2003 and December 2010. Among 2,237 antiviral‐naïve HCV‐infected patients with curatively resected HCC, there were 213 patients receiving antiviral treatment with pegylated interferon plus ribavirin for 16 weeks or more after surgery (treated cohort). These treated patients were matched 1:4 with 852 controls who were never treated for HCV infection (untreated cohort) by age, gender, cirrhosis, and the elapsed time between surgery and antiviral therapy. Cumulative incidences of and hazard ratios for recurrent HCC were calculated after adjusting for competing mortality. The recurrence rate of HCC was significantly lower in the treated than untreated cohort, with 52.1% (95% confidence interval [CI], 42.0‐62.2%) and 63.9% (95% CI, 58.9‐68.8%) after 5 years of follow‐up, respectively (P = 0.001). The number needed to treat for one fewer recurrent HCC at 5 years was 8. The association between postoperative antiviral treatment and risk of recurrent HCC was independent of adjustment for multiple covariates, with an adjusted hazard ratio of 0.64 (95% CI, 0.50‐0.83). Stratified analyses revealed that the attenuation in recurrence risk was greater in patients younger than 60 years and those without cirrhosis or diabetes. Conclusion: Postoperative pegylated interferon plus ribavirin is associated with reduced recurrence of HCC in patients with HCV infection. Age, liver cirrhosis, and diabetes mellitus appear to modify this association. (HEPATOLOGY 2013)

Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial

OBJECTIVES The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.

Delayed endoscopy as a risk factor for in-hospital mortality in cirrhotic patients with acute variceal hemorrhage

Background and Aims:  Risk factors for mortality in acute variceal hemorrhage remain incompletely understood. Whether endoscopy timing is associated with risk of mortality has not been investigated. We aimed to investigate risk factors for in‐hospital mortality in cirrhotic patients with acute variceal hemorrhage, with emphasis on endoscopy timing.

Long‐term risk of recurrent peptic ulcer bleeding in patients with liver cirrhosis: A 10‐year nationwide cohort study

Peptic ulcer bleeding leads to substantial morbidity and mortality in patients with liver cirrhosis, but their long‐term risk of recurrent bleeding remains elusive. This nationwide cohort study aimed to elucidate the association between cirrhosis and recurrent peptic ulcer bleeding by analyzing the Taiwan National Health Insurance Research Database. We enrolled a total of 9,711 patients who had cirrhosis with clinical complications of portal hypertension from all patients (n = 271,030) hospitalized for peptic ulcer bleeding between January 1997 and December 2006, along with 38,844 controls who were matched at a 1:4 proportion for age, sex, and antisecretory agents. We accounted for death as the competing cause of risk when calculating the cumulative incidences and hazard ratios of recurrent bleeding during the 10‐year study period. Overall, patients with cirrhosis had a significantly higher death‐adjusted rebleeding rate compared with controls (1 year, 14.4% versus 11.3%; 5 years, 26.1% versus 22.5%; 10 years, 28.4% versus 27.1%; P < 0.001). The modified Cox proportional hazard model verified that cirrhosis was significantly associated with peptic ulcer rebleeding (adjusted hazard ratio, 3.19; 95% confidence interval, 2.62‐3.88), but also uncovered a seemingly paradoxical interaction between cirrhosis and age. Multivariate stratified analysis further revealed that the rebleeding risk after adjustment for death diminished with age in patients with cirrhosis, whose risk of death far exceeded that of rebleeding when they grew old. Conclusion: Liver cirrhosis is associated with long‐term risk of recurrent peptic ulcer bleeding, although the risk declines with age because of death being the competing cause. Effective therapy should be sought to reduce this excessive risk in these critically ill patients, particularly for those at younger age with longer life expectancy. (HEPATOLOGY 2012)

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.

Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria

Background and objective Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population. Methods Patients with dyspepsia and healthy subjects who underwent gastric cancer screening were enrolled in this multicentre study from 2010 to 2012. All patients were evaluated by questionnaire, oesophagoduodenoscopy, histological examination and Helicobacter pylori tests. Subgroups of FD were classified according to the Rome III criteria. Psychiatric stress was assessed by the short form Brief Symptom Rating Scale. CagA and VacA genotypes were determined by PCR. Results Of 2378 patients screened for eligibility, 771 and 491 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. 298 (60.7%) and 353 (71.9%) individuals were diagnosed with EPS and PDS, respectively, whereas 169 (34.4%) had the overlap syndrome. As compared with 1031 healthy controls, PDS and EPS shared some common risk factors, including younger age (OR 0.95; 99.5% CI 0.93 to 0.98), non-steroidal anti-inflammatory drugs (OR 6.60; 99.5% CI 3.13 to 13.90), anxiety (OR 3.41; 99.5% CI 2.01 to 5.77) and concomitant IBS (OR 6.89; 99.5% CI 3.41 to 13.94). By contrast, H. pylori (OR 1.86; 99.5% CI 1.01 to 3.45), unmarried status (OR 4.22; 99.5% CI 2.02 to 8.81), sleep disturbance (OR 2.56; 99.5% CI 1.29 to 5.07) and depression (OR 2.34; 99.5% CI 1.04 to 5.36) were associated with PDS. Moderate to severe antral atrophy and CagA positive strains were also more prevalent in PDS. Conclusions Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies.

Intestinal Infestation with Ancylostoma ceylanicum

Under magnifying endoscopy, a worm is seen hooking its head into the intestinal mucosa. The parasite was removed and identified as Ancylostoma ceylanicum, a nematode that is endemic to Southeast Asia.