Race affects healing of erosive oesophagitis in patients treated with proton pump inhibitors.

BACKGROUND: Erosive oesophagitis appears to be more common in white vs. nonwhite patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the association between race and erosive oesophagitis healing in patients with GERD treated with once-daily proton pump inhibitors (PPIs). METHODS: Data from five double-blind trials of once-daily treatment with esomeprazole 40mg vs. omeprazole 20mg or lansoprazole 30mg for erosive oesophagitis healing (evaluated at weeks 4 and 8 by endoscopy) were pooled and stratified by baseline race and Los Angeles (LA) severity grade. Multiple logistic regression models were fit with erosive oesophagitis healing (dependent variable) and race (independent variable), with adjustments for treatment, study, baseline LA grade, age, gender, BMI, Helicobacter pylori status, hiatal hernia and interactions of these factors with race. RESULTS: Of 11,027 patients, 91% were white. Nonwhite (n=978) and black (n=613) patients were less likely to have severe baseline erosive oesophagitis (LA grade C or D) than white patients [adjusted OR: 0.69 (95% CI, 0.61-0.79) and 0.67 (0.57-0.78), respectively; P<0.0001]. At week 8, nonwhite and black patients had lower healing rates than white patients [OR: 0.75 (0.63-0.89) and 0.67 (0.54-0.83), respectively; P≤0.001]. Greater odds of healing were associated with less severe baseline LA grade, increasing age, hiatal hernia, esomeprazole treatment (vs. lansoprazole or omeprazole) and lansoprazole treatment (vs. omeprazole) (all P≤0.0009); no factor interacted significantly with race. CONCLUSIONS: Nonwhite patients with GERD had less severe baseline erosive oesophagitis, but were less likely than white patients to have erosive oesophagitis healing after 8-week PPI therapy.

Clinical trial: gastric acid suppression in Hispanic adults with symptomatic gastro-oesophageal reflux disease - comparator study of esomeprazole, lansoprazole and pantoprazole.

BACKGROUND: Hispanic-Americans are a rapidly growing population in the United States, yet gastro-oesophageal reflux disease (GERD) is not well studied in this population. AIM: To compare the efficacy of esomeprazole, lansoprazole and pantoprazole in suppressing gastric acid, including the area of the 'acid pocket,' in Hispanics with GERD. METHODS: In this open-label, 3-way crossover study, 83 Hispanics with symptomatic GERD were randomized to 1 of 6 possible treatment sequences of three 5-7-day dosing periods with esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg daily separated by 10-17-day washout periods. Intragastric pH was measured for 24 h using dual probes with a distal and proximal (area of the 'acid pocket') electrode. RESULTS: Esomeprazole suppressed intragastric acid (pH >4.0) significantly longer over 24 h (primary end point) compared with lansoprazole and pantoprazole (P < 0.0001), and proximal gastric acid (pH >4.0) significantly longer over 24 h compared with lansoprazole (P < 0.05) and pantoprazole (P < 0.0001). CONCLUSIONS: Esomeprazole was more effective than lansoprazole and pantoprazole in suppressing gastric acidity at both intragastric distal and proximal (area of the acid pocket) sites in Hispanics with GERD. Future studies are warranted to understand better the role of the acid pocket in GERD (Clinical trial numbers: D9612L00106; ClinicalTrials.gov: NCT00410592).

Objective ranking of fibrosis in standard histologic sections of human neonatal liver: applicability to alpha1-antitrypsin deficiency.

BACKGROUND: The etiologic heterogeneity of fibrotic liver disease has resulted in the formulation of diverse, often disease-specific, classification systems for biopsy assessment, based on tissue morphology and staining. Their qualitative nature and observer dependency remain a concern, and no classification exists for several significant conditions--for example, alpha1-antitrypsin deficiency (alpha1-ATD). The authors propose a disease- and morphology-independent numeric ranking system to objectively quantify fibrosis in a standard histologic section, based on its content of protein amino acids. This PNC system is applied to two cases of alpha1-ATD liver fibrosis. METHODS: High-performance liquid chromatography separation of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)-labeled acid hydrolysate of an individual needle biopsy section, followed by the calculation of specific amino acid ratios to eliminate confounding variables. RESULTS: As required by the PNC system, three numeric values were identified per tissue section, one increasing (P quotient), one decreasing (N quotient), one constant (C quotient) as fibrosis progresses, assessed by calibration against Knodell-staged samples. Generated for the alpha1-ATD sections, these three coordinates numerically referenced the degree of fibrosis in a manner that in each case was consistent with the histologic evaluation, the laboratory values, and the clinical course. CONCLUSIONS: Numeric, objective referencing of the degree of fibrosis in routine liver biopsy sections, based on the PNC system, is technically possible.

Mosaic trisomy 14 with hepatic involvement.

Mosaic trisomy 14 in liveborns is rare and may be accompanied by uniparental disomy in the euploid cell line. We report the case of a 6 month old male with growth failure, microcephaly, macroglossia, developmental delay, hypotonia, congenital heart disease, neonatal hepatitis, cryptorchidism, talipes equinovarus, limb length asymmetry, bilateral overriding of 1st by 2nd toe, and extended abnormal pigmentation in a linear-whorl distribution. The proband's karyotype in peripheral lymphocytes and skin fibroblasts was mos47,XY,+14/46,XY. Parental blood chromosomes were normal. Molecular analysis excluded uniparental disomy in the euploid cell line of the proband.