PREVALENCE OF OESOPHAGEAL EOSINOPHILS AND EOSINOPHILIC OESOPHAGITIS IN ADULTS: THE POPULATION-BASED KALIXANDA STUDY
Eosinophilic oesophagitis is an important condition, but its prevalence in the general population remains unknown. Ronkainen
et al determined the prevalence of eosinophilic oesophagitis and its association with upper gastrointestinal symptoms and gastro-oesophageal
reflux disease in an adult Swedish population (the Kalixanda study). A random sample of 2860 adults was surveyed using the
validated Abdominal Symptom Questionnaire. An upper gastrointestinal endoscopy was performed in a representative sample of
1000 of the responders to the questionnaire. Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1), just over
half of whom had no troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95%
CI 0.01 to 0.80) (see fig). Erosive oesophagitis (odds ratio (OR) = 2.99) and absence of dyspepsia (OR = 0.23) and Helicobacter pylori infection (OR = 0.41) were independent predictors for the presence of eosinophils in the oesophagus. This study provides
the first robust current community prevalence estimates, which appear higher than previously appreciated.
See p 615
GASTRITIS STAGING IN CLINICAL PRACTICE: THE OLGA STAGING SYSTEM
Existing gastritis classification systems lack simplicity and prognostic information. An international group, the Operative
Link on Gastritis Assessment (OLGA) proposed the OLGA staging system for reporting gastric histology. This staging system
integrates the atrophy score and the atrophy topography (see fig). Rugge et al tested in a prospective, cross-sectional study whether OLGA staging consistently stratified patients according to their cancer
risk and provided clear prognostic/therapeutic information. OLGA staging for gastric cancer risk (0–IV) and gastritis grading
(overall score of the inflammatory infiltrate, grade 1–4) were applied to 439 prospectively-enrolled, consecutive patients
with dyspepsia who underwent endoscopy with standardised biopsy sampling. All significant lesions were recorded. Results were
presented as stage, including antral (A) and corpus (C) atrophy scores, and Helicobacter pylori status (eg, A = 3; C = 2: stage IV; Hp+ve). Benign conditions (including duodenal ulcers, p<0.001) consistently clustered
in stages 0–II, whereas all neoplastic (invasive and non-invasive) lesions clustered in stages III–IV (p<0.001). The OLGA
staging system combined with H pylori status provides useful prognostic data that could aid the treatment and management of patients.
See p 631
NEONATAL FAECAL ESCHERISCHIA COLI AND CLOSTRIDIUM DIFFICILE ASSOCIATED WITH DEVELOPMENT OF ECZEMA
The bacterial flora in neonates is believed to play an important role in the development of the immune system. This study
is part of a large prospective birth cohort study in the Netherlands examining the causes of atopy. Stool samples were analysed
for bacterial DNA to assess total bacterial numbers and numbers of Bifidobacteria spp, Bacteroides fragilis, Escherischia coli, Clostridium difficile and Lactobacillus spp. At 1 month old most infants had detectable Bifidobacteria, E coli and B fragilis but only one third had Lactobacilli spp and one quarter had C difficile. By 2 years old, 30% had experienced eczema (defined as an itchy rash, excluding nappy rash or rash around the eyes/scalp).
There was an increased risk of eczema in those with C difficile and E coli, which showed a dose–response (see fig). The cause of the link is uncertain, but could reflect bacterial induced alterations
in gut permeability leading to a breach of immune tolerance.
See p 661
MODELLING COST EFFECTIVENESS OF COLORECTAL CANCER SCREENING
Colorectal cancer (CRC) is expensive both in healthcare costs and human suffering. As most European countries start to develop
population-based screening programmes, there are considerable uncertainties about the optimal methods and timing for the screening
test. This paper models the impact of screening by faecal occult blood testing (FOBT) and/or flexible sigmoidoscopy using
existing data. The model shows that at best deaths from CRC could be reduced by 33%. As there is considerable uncertainty
about many parameters in the model, including the rates of transition from adenoma to carcinoma, the authors produce a range
of possible values for each screening method. Flexible sigmoidoscopy once at 60 years, together with biennial FOBT from age
61–70, appears the most cost–effective (see fig). However, there is considerable uncertainty in the likely gain in QALY (quality
adjusted years) compared with no screening and plainly there is a need for more adequate data to allow better prediction of
the optimum techniques.
See p 677
IMPORTANCE OF HEPATITIS B VIRUS (HBV) GENOTYPE FOR PREDICTING RESPONSE TO PEGINTERFERON α-2A, LAMIVUDINE OR COMBINATION TREATMENT
HBV e antigen (HBVeAg) negative infection, which is an important cause of death from cirrhosis and hepatoma, is characterised
by progressive, silent liver damage associated with continued viral replication. While the success of antiviral treatment
for HBeAg-positive patients is associated with low serum HBV DNA levels and high serum alanine aminotransferase (ALT), whether
this is true for patients who are HBVeAg negative is uncertain. The current paper analysed predictors of response in a randomised
trial of 537 such patients, treated with either peginterferon α-2a and/or lamivudine. As expected, high ALT, female gender,
younger age and low levels of HBV DNA all predicted better response. The new finding was that geneotype D did significantly
worse with either monotherapy. Overall, combination therapy was not significantly better than monotherapy, but subgroup analysis
showed the combination improved genotype D response from 16% to 37%. If these findings are replicated, they suggest that genotype
should strongly influence choice of treatment for HBVeAg negative patients.
See p 699
ADENOVIRUS-MEDIATED EXPRESSION OF BMP-7 SUPPRESSES THE DEVELOPMENT OF LIVER FIBROSIS IN RATS
Accumulation of extracellular matrix materials is the basis of liver cirrhosis and this is particularly driven by transforming
growth factor β (TGFβ). The fibrogenic effects of TGFβ could be antagonised by bone morphogenetic factor 7 (BMP-7), which
is a member of the TGFβ superfamily and has essential roles during embryogenesis. Kinoshita et al examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGFβ in vitro and in vivo.
They used primary cultured rat stellate cells and the LX-2 human stellate cell line, in addition to a liver fibrosis model
induced by repetitive intraperitoneal injection of thioacetamide. Induction of BMP-7 by Ad-BMP-7 infection decreased the expression
of collagen 1A2 messenger RNA and smooth muscle α-actin via Smad 1/5/8 phosphorylation. In rats administered Ad-BMP-7 via
the tail vein, hydroxyproline content and the areas stained by Sirius red dye in the liver were significantly reduced compared
with controls (see fig). The approach is hoped to ultimately contribute towards gene therapy for hepatic fibrosis.
See p 706