Helicobacter pylori infection and associated stomach pathology in the adult general population

The discovery of H. pylori infection has had a tremendous impact on the understanding and treatment of upper gastrointestinal diseases. It causes gastritis, sometimes developing to atrophy and intestinal metaplasia (IM), both considered as premalignant conditions and it is an important risk factor for peptic ulcer and non-cardia gastric cancer. The purpose of this thesis was to explore aspects of the infection in the general adult population. A random sample of 3,000 adults aged 20-80 years (mean age 50.4), from two Swedish municipalities (n=21,610) was surveyed using a validated postal abdominal symptom questionnaire with a response rate of 74%. A representative sub-sample of the responders (n=1,000) was investigated, in random order, by upper endoscopy and histology. Blood samples were drawn for H. pylori serology and assessment of other biomarkers. Medical history was taken and repeated recording of symptoms were made.

Diagnosis of current infection can be made by histology and/or culture, while serology also detects past infection. The diagnosis of atrophic gastritis and IM is based on histology. We found that 43.0% of all individuals were positive on H. pylori serology, 33.9% had signs of current infection on either histology or culture, and 9.3% were seropositive but negative on histology and culture. Corpus atrophy and IM was found in 10% and 13%, respectively, in those with current infection, and in a significantly higher proportion, 17% and 21%, respectively, in those with only serological evidence of past infection. Among those who were sero-negative, the corrsponding proportion of individuals were 1% and 2%, respectively.

Gastric precancerous lesions (atrophy and IM) are often found in the junctional (incisura and gastro-esophageal junction ) mucosa. Non-cardia gastric cancer is most common in the antral mucosa, and thus a proximal antralization might imply increased cancer risk. We found antralization at the incisura in 45% of all 1000 subjects and it was significantly more common in H. pylori infected and in smokers. Atrophy and/or IM were present in 9.8% of those with antralization. In the cardia, 7.3% had corpus mucosa and 92.7 % had cardia mucosa. Among the latter subjects, 10.3 % had atrophy/IM compared to 2.8 % among the former, p=0.04.

Diagnosing H. pylori infection and atrophy by means of serological biomarkers has some advantages. The overall agreement between histology and serological biomarkers for diagnosing corpus atrophy in this study was 96%. The sensitivity and specificity of markers for atrophic gastritis were 71% and 98%, respectively, and the Positive Likelihood ratio was 35.5. Only 0.8% of individuals with no histological evidence of corpus atrophy were positive for atrophy based on biomarker assessment. Biomarkers detected corpus atrophy in 6.6% of all study subjects. Triple therapy for H. pylori eradication includes two antimicrobials and a proton pump inhibitor. Knowledge of antimicrobial resistance is crucial. We found that 16.2 % of the H. pylori strains were resistant to metroniazole, 1.5 % to clarithromycin, 0 % to amoxicillin and 0.3 % to tetracycline.

Conclusions: The prevalence of current H. pylori infection in a random sample of an adult population in two municipalioties in Sweden, was 33.9% and a further 9.3% had serological evidence of past H pylori infection. The prevalence of corpus atrophy and/or IM was higher among the latter. We found that Antralization is related to H. pylori infection and smoking. Serological biomarkers for current and past H pylori-infection are useful for corpus atrophy detection. Antibiotic resistance to H. pylori was low in the study population.

List of scientific papers

I. Storskrubb T, Aro P, Ronkainen J, Vieth M, Stolte M, Wreiber K, Engstrand L, Nyhlin H, Bolling-Sternevald E, Talley NJ, Agréus L (2005). A negative Helicobacter pylori serology test is more reliable for exclusion of premalignant gastric conditions than a negative test for current H. pylori infection: a report on histology and H. pylori detection in the general adult population. Scand J Gastroenterol. 40(3): 302-11.
https://pubmed.ncbi.nlm.nih.gov/15932171

II. Storskrubb T, Talley NJ, Walker MM, Aro P, Ronkainen J, Sipponen P, Vieth M, Stolte M, Agréus L (2008). Cancer risk factors in gastric incisura and cardia: An adult endoscopic population based study (Kalixanda). [Submitted]

III. Storskrubb T, Aro P, Ronkainen J, Sipponen P, Nyhlin H, Talley NJ, Engstrand L, Stolte M, Vieth M, Walker MM ,Agréus L (2008). Serum biomarkers provide an accurate and non-invasive screening method for diagnosis of atrophic gastritis compared with gold standard histology in a large population sample. The Kalixanda study. [Submitted]

IV. Storskrubb T, Aro P, Ronkainen J, Wreiber K, Nyhlin H, Bolling-Sternevald E, Talley NJ, Engstrand L, Agréus L (2006). Antimicrobial susceptibility of Helicobacter pylori strains in a random adult Swedish population. Helicobacter. 11(4): 224-30.
https://pubmed.ncbi.nlm.nih.gov/16882324