Cheng-Hao Tseng

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.

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.

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.

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.

Endoscopic submucosal dissection for early esophageal neoplasia: A single center experience in South Taiwan

BACKGROUND/PURPOSE Endoscopic submucosal dissection (ESD) is an advanced endoscopic procedure to resect early gastrointestinal neoplasm. It is technically more difficult and risky when used to treat early esophageal tumors. We report our experiences related to performing ESD for early esophageal neoplasia. The efficacy, complications, and outcome were also analyzed. METHODS From December 2007 to April 2010, 22 patients with documented early esophageal neoplasm underwent ESD. All patients completed a meticulous endoscopic examination using conventional endoscopy followed by narrow-band imaging. Lugols staining was performed to identify the margin of the suspicious lesion. Insulation-tipped diathermic knife 2 was used for ESD. RESULTS A total of 26 neoplastic lesions (including 13 tumors with high-grade dysplasia, 12 tumors with squamous cell carcinoma, and one tumor with adenocarcinoma) in 22 patients were enrolled. All patients were men. The mean age was 47.6 ± 8.6 years (range, 30-68 years). The mean size of tumors was 33.7 ± 21.7 mm (range, 8-80 mm). ESD was performed for 24 lesions in 20 patients. The mean size of resected specimens was 43.1 ± 19.2 mm (range, 15-90 mm). The mean operation time was 92.7 ± 69 minutes (range, 30-310 minutes). There were three ESD-related complications, including one with delayed bleeding, one with subcutaneous emphysema, and one with perforation. Two patients received additional operations after ESD due to deep submucosal invasion by cancer. Three lesions in two patients (12.5%) developed post-ESD esophageal stricture that needed repeated endoscopic bougination. There was no procedure-related mortality. No local recurrence was found during the follow-up period. CONCLUSION ESD is a promising local curative treatment option for early esophageal neoplasia in Taiwan. However, this procedure may result in complications that are worth noting, especially post-ESD esophageal stricture. Education regarding this procedure and more hands-on training will facilitate endoscopists to improve the outcomes of patients undergoing this procedure.

Cryptococcal meningitis in pediatric systemic lupus erythematosus

Cryptococcal meningitis is an uncommon but often fatal complication of systemic lupus erythematosus (SLE). We report on a 13‐year‐old girl with SLE using high‐dose prednisolone for several months, presented to us with low grade fever, intermittent vomiting and headache. Physical examination, including papilloedema and meningeal irritation, was unremarkable. Serum and cerebrospinal fluid (CSF) cryptococcal antigen titer was 1 : 128 by latex agglutination method. CSF culture yielded Cryptococcus neoformans. We used amphotericin B deoxycholate (a cumulative dose of 1.95 gm) and fluconazole (200 mg day−1) for 6 weeks. Clinical response was good. Then, we continued fluconazole 200 mg per qd as suppressive therapy for thirty‐four months. There were no neurological sequelae or relapse after 20‐month follow‐up. Timely diagnosis and effective antifungal therapy could improve the prognosis of cryptococcal meningitis in SLE patients.

The benefit of pretreatment esophageal screening with image-enhanced endoscopy on the survival of patients with hypopharyngeal cancer.

BACKGROUND Synchronous esophageal cancers can suppress the survival of patients with hypopharyngeal cancers. Esophageal screening with the image-enhanced endoscopy may identify more synchronous cancers while there is no evidence to support its benefit on survival. METHODS A total of 281 and 320 patients were diagnosed with hypopharyngeal cancer before and after the policy of routine esophageal screening. Primary outcome measures were overall survival. RESULTS Among those who received screening, 49 patients (49/180, 27.2%) had synchronous esophageal cancers; treatment planning was changed in 42 (23.3%). Before and after the policy, percentages of stage I-II synchronous cancers were 20% (3/15) and 53.1% (26/49), respectively. Adjunctive therapies for synchronous cancers have led to a better survival after the policy than before (P = 0.002). The Cox regression model quantified a survival benefit of 29% (95% CI: 11-43%) when adjusting for TNM stage of hypopharyngeal cancer. In post-policy period, the survival was better for those who chose screening than those who did not (HR: 0.57, 95% CI: 0.41-0.79). Among those without screening, there was no difference between the pre- and post-policy periods (HR: 0.96, 95% CI: 0.74-1.26). CONCLUSIONS Patients with hypopharyngeal cancers may benefit from the esophageal screening with image-enhanced endoscopy through the better detection of early-stage synchronous cancers.

Entecavir versus lamivudine in the treatment of chronic hepatitis B patients with hepatic decompensation.

BACKGROUND Lamivudine has been widely used in chronic hepatitis B patients with hepatic decompensation, but its use is limited by drug resistance. This outcome research aimed to investigate the comparative efficacy and safety of entecavir versus lamivudine in decompensated patients. METHODS Between November 2004 and February 2010, 126 consecutive treatment-naive patients received either entecavir (n=53) or lamivudine (n=73) for decompensated chronic hepatitis B. All patients presented with both hyperbilirubinaemia and coagulopathy. Primary outcome was mortality within 1 year; secondary outcomes included liver-related mortality, biochemical and virological response, and improvement of hepatic dysfunction. RESULTS Both treatment groups were comparable in baseline characteristics. A total of 19 (35.8%) entecavir and 33 (45.2%) lamivudine receivers expired within 1 year, respectively (P=0.29, log rank test). Age (hazard ratio [HR] 1.04 per year, 95% CI 1.01, 1.06), cirrhosis (HR 2.07, 95% CI 1.02, 4.23), and international normalized ratio for prothrombin time (HR 1.44, 95% CI 1.20, 1.74) were independent baseline predictors for all-cause mortality. Antiviral therapy was also unrelated to liver-specific death. However, more patients taking entecavir tended to attain aminotransferase normalization (76.5% versus 52.5%; P=0.05) and viral DNA undetectability (100% versus 58.3%; P=0.06). Moreover, entecavir was associated with significantly greater reduction of the model for end-stage liver disease scores (median 10.0 versus 4.3; P=0.02). Overall, 3 (7.5%) lamivudine but no entecavir users acquired drug resistance in 1 year (P=0.25). CONCLUSIONS Entecavir as compared with lamivudine is similar in the effect on short-term mortality but is associated with greater clinical improvement among chronic hepatitis survivors who recovered from hepatic decompensation.

Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B

OBJECTIVES We aimed to identify determinants of hepatocellular carcinoma (HCC) in cirrhotic patients who received nucleos(t)ide analogues for chronic hepatitis B (CHB). PATIENTS AND METHODS This retrospective-prospective study screened all patients (n = 1630) who received antiviral therapy for CHB between 1 September 2007 and 31 March 2013 at the E-Da Hospital and enrolled 210 consecutive cirrhotic patients with pretreatment viral DNA >2000 IU/mL. Those who developed HCC within 3 months of treatment were excluded. All participants were observed until occurrence of HCC, death or 1 January 2014. The incidence and determinants of HCC were estimated using competing risk analyses adjusted for mortality. RESULTS Thirty-five (16.7%) patients developed HCC during a median follow-up of 25.2 months (IQR, 16.3-37.3 months), with a cumulative incidence of 24.1% (95% CI, 16.3%-32.0%) at 5 years. Multivariate-adjusted analyses identified age >55 years [adjusted hazard ratio (HR), 2.19; 95% CI, 1.03-4.66], male gender (adjusted HR, 3.07; 95% CI, 1.05-9.02), model for end-stage liver disease (MELD) score >12 points (adjusted HR, 2.16; 95% CI, 1.10-4.23) and diabetes mellitus (DM; adjusted HR, 3.49; 95% CI, 1.54-7.91) as independent risk factors after adjusting for multiple covariates, including antidiabetes medication. A scoring formula that used information on age, gender, MELD score, DM and antidiabetes regimen significantly discriminated patients at high or low risk of HCC, with sensitivity and specificity of 82.9% and 62.3%, respectively. CONCLUSIONS Age, gender, hepatic dysfunction, DM and medication for DM are baseline factors that stratify the risk of HCC in cirrhotic patients who receive nucleos(t)ide analogues for CHB.