Background & Aims The efficacy of treatment of Helicobacter pylori infection has decreased steadily due to 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. Methods We performed a large-scale, multi-hospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naïve (n=450) or treatment-experienced (n=168) patients with H pylori infection. Treatment-naïve 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 using the 13C–urea breath test. We evaluated factors associated with treatment outcomes. Results In the intention-to-treat 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%). 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. Conclusions HDDT is superior to standard regimens as empiric first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov no: NCT01163435.

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Contrast-enhanced ultrasound (CEUS) imaging has been a reliable clinical method of detecting three vascular contrast phases and characterizing focal liver lesions. Previous results were all from human (i.e., clinical studies). The main purpose of this study was to extend this to small animals and to investigate the feasibility of using CEUS in preclinical research. Specifically, high-frequency (40 MHz) ultrasound liver imaging with albumin-shelled microbubbles was employed to detect the three vascular contrast phases and characterize focal liver lesions that developed in thirteen Hepatitis B virus X (HBx) transgenic mice at around 14 to 16 months of age. Previous studies indicated that 90-100% incidence of hepatocellular carcinoma (HCC) was observed in HBx transgenic male mice. After injecting the contrast agent, the time-intensity curves (TICs) of focal liver lesions, vessels in focal liver lesions and surrounding liver parenchyma tissues were measured for 30 minutes. The peak of mean intensity relative to the baseline increased 7.36 dB (p < 0.02). On the other hand, the mean contrast between the focal liver lesion and the liver parenchyma increased by 7.74 (p < 0.05) dB, thus allowing clear detection ofthe lesion margin. Histopathology investigations confirmed the development of the lesion in these mice. In addition, guidelines of European Federation of Societies for Ultrasound in Medicine and Biology were followed as an attempt to characterize features of the TICs in mice. The arterial phase was defined as 2 to 60 seconds post contrast injection, and the parenchyma phase was defined as the time period from 10 to 30 minutes post contrast injection. Comparing the imaging with the pathology results, the sensitivity, specificity and accuracy of CEUS for the detection of malignant focal liver lesion in HBx transgenic mice were 91%, 100% and 92%. These results demonstrated that high-frequency CEUS imaging potentially can be used for detecting the three vascular contrast phases of malignant focal liver lesions and characterizing malignant focal liver lesions in mice. Thus can be a valuable tool in preclinical research.