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Hypochlorhydria (gastric pH >4) increases susceptibility to diarrhoea, iron deficiency, and gastric cancer. We sought to clarify the prevalence of this condition and its predisposing factors in Zambia by pooling data from previous studies conducted in hospital and community settings. Gastric pH was measured in participants from five separate studies by collecting gastric aspirate from fasted adults and children under 3 years of age undergoing gastroscopy. Gastric pH was correlated with serological testing for Human Immunodeficiency Virus (HIV) and Helicobacter pylori (H. pylori) infections. We studied 597 individuals (487 adults and 110 children). Hypochlorhydria was present in 53% of adults and 31% of children. HIV infection was detected in 41% of adults and 11% of children. H. pylori serology was available for 366 individuals: 93% of adults and 6% of children were seropositive. In univariate analysis, hypochlorhydria was significantly associated with HIV seropositivity (OR 1.7; 95% CI 1.2-2.4; p = 0.004) and H. pylori antibody seropositivity (OR 4.9; 95% CI 2.8-8.6; p<0.0001), and with advancing age in HIV negative individuals (p = 0.0001). In multivariable analysis, only H. pylori was associated with hypochlorhydria (OR 4.0; 95% CI 2.2-7.2; p<0.0001) while excluding possible exposure to proton pump inhibitors. Hypochlorhydria is common in our population, with H. pylori being the dominant factor. Only young HIV seronegative individuals had a low prevalence of hypochlorhydria. This may have implications for the risk of other health conditions including gastric cancer.

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

With the exception of South Africa, inflammatory bowel disease (IBD) has long been considered uncommon in sub-Saharan Africa (SSA) with a dearth of peer-reviewed publications from the subcontinent. This most likely reflects underreporting as some cases may be missed due to the high burden of infectious diseases which may closely mimic IBD. In addition, many countries in SSA have limited endoscopic capacity, inadequate access to diagnostic imaging and a notable scarcity of histopathologists, radiologists and gastroenterologists. Beyond these obstacles, which significantly impact patient care, there are many other challenges in SSA, particularly the unavailability of key IBD therapies. In this review, we discuss barriers in diagnosing and managing IBD in SSA, as well as some of the initiatives currently in place to address these short comings.

ObjectivesEnvironmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE.MethodsWe optimized a 13C-sucrose breath test (13C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE.ResultsFully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2–3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13C-sucrose digestion, reducing 4 h 13CO2 breath recovery by > 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13CO2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height ( r = 0.72; P < 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13C-SBT and villus height or measured sucrase activity in pinch biopsies.ConclusionA 13C-SBT was developed which was easy to perform, generated clear enrichment of 13CO2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.

IntroductionScarcity of IBD in sub-Saharan Africa may reflect both differing population genetic disposition and exposure to environmental factors, however, little data relating to this has been published to date. Our aim was to perform genetic analyses of IBD in Zambian subjects.MethodsSaliva was collected in Oragene DNA collection tubes (DNAGenotek, Ottawa, Canada) from IBD cases and controls in the GI clinic of a tertiary hospital in Zambia and stored at 4C. DNA was extracted using the NucleoSpin Tissue kit (Macherey-Nagel) and genotyped using the H3Africa Consortium Array (Illumina). Genetic association for genotyped and imputed SNPs case-control binary variable was performed using logistic regression including principal components for population sub-structure as covariates (PLINKv1.9). Variant effect prediction and functional analysis were performed using the Ensembl platform and ClueGO software.ResultsGenotyping was performed on 16 cases (14 UC, 2 Crohn’s) and 29 controls. Variants were present on LSAMP and ELMO1 which have previously been described as novel risk loci for UC and IBD respectively in African American cohorts.(1, 2) A variant on IL23R (rs790631:G>A, allele frequency 8.6% cases and 25% controls, (p=3.44 x10-2, OR 0.283)) has previously been associated with increased risk of Crohn’s in a Caucasian population (3). No variants on NOD2, ATG16L1 or CARD9 were present.The SNP with the strongest association with IBD (OR 9.51) was rs3763236:G>A (allele frequency 63.8% cases and 15.6% controls), an intron variant on CNPY3, which encodes a toll-like receptor-specific chaperone protein and has not previously been identified as a risk locus for IBD. Functional pathway analysis (figure 1) shows pathways with significant enrichment which included Type 1 diabetes and the extra-cellular matrix which have previously been implicated in IBD.ConclusionsIBD risk loci that have previously been identified as African specific in African American cohorts are reflected in this small cohort of sub-Saharan African patients. These findings suggest that additional and larger studies are needed to determine the genetic architecture of under researched populations in which IBD is emerging.ReferencesBrant SR, Okou DT, Simpson CL, Cutler DJ, Haritunians T, Bradfield JP, et al. Genome-wide association study identifies African-specific susceptibility loci in African Americans with inflammatory bowel disease. Gastroenterology. 2017;152(1):206–17.e2.Cordero RY, Cordero JB, Stiemke AB, Datta LW, Buyske S, Kugathasan S, et al. Trans-ancestry, bayesian meta-analysis discovers 20 novel risk loci for inflammatory bowel disease in an African American, East Asian, and European cohort. Hum Mol Genet. 2022.Taylor KD, Targan SR, Mei L, Ippoliti AF, McGovern D, Mengesha E, et al. IL23R haplotypes provide a large population attributable risk for Crohn’s disease. Inflamm Bowel Dis. 2008;14(9):1185–91.Abstract P62 Figure 1Functional pathways with significant associations[Figure omitted. See PDF]

BackgroundAdipose tissue has a regulatory role in innate and adaptive immune processes and obesity has been linked to non-response to medical therapies and disease progression in patients with IBD.1 Few studies have estimated the prevalence of obesity in patients with IBD in the UK and none have assessed associations with geographical determinants of health.We sought to define in adult patients with IBD treated with infliximab and vedolizumab who were recruited to the UK CLARITY IBD2 study the:Prevalence of overweight and obesityDemographic, geographic and disease factors associated with obesityInfluence of obesity on mood and anxietyRelationship between obesity and geographical determinants of healthMethodsObesity was defined according to World Health Organisation body mass index (BMI) definitions for adults. Mood and anxiety disorders were assessed using the Patient Health Questionnaire (PHQ-8) and General Anxiety Disorder Assessment (GAD-7). We collapsed postcodes to Level Super Output Areas and extracted income decile from the index of multiple deprivation. We extracted geographical determinants of health data from the Access to Healthy Assets and Hazards [AHAH] (Version 3).3 Statistical analyses were undertaken comparing patients with obesity with those who were overweight or had a normal BMI. Multivariable analyses were restricted to patients living in England.ResultsBMI data was available in 98.3% (6664/7020). Overall, 32.3% (2083/6664 [95% CIs 31.1-33.4%]) and 25.9% (1672/6664 [95% CIs 24.8-27.0%]) were overweight and obese, respectively. The highest prevalence of obesity was observed in the West Midlands and the lowest prevalence in London and Scotland.Multivariable logistic regression analysis demonstrated that obesity was independently associated with female sex, older age, non-Asian ethnicity, non-smoking and active IBD. Obesity was associated with all severities of depression but not anxiety. Obesity did not vary by urban or rural location. Obesity was significantly associated with higher deprivation scores and the overall AHAH score. Factors associated with obesity are shown in figure 1.Abstract O18 Figure 1ConclusionsObesity is common in UK patients living with IBD and is independently associated with female sex, older age, non-Asian ethnicity, geographical region, non-smoking, active IBD and deprivation.ReferencesKennedy NA, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol. 2019 May;4(5):341-353.Kennedy NA, et al. Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab. Gut 2021;70:865-875.Access to Healthy Assets & Hazards (AHAH) Version 3. Consumer Data Research Centre, 2024 [cited 2024 Nov 18].

IntroductionOesophageal varices develop as a consequence of portal hypertension in patients with cirrhosis and account for around 10% of admissions with acute GI bleeding in the UK with a significant in-hospital mortality rate of 15%.1 In 2015–2016 the BSG and NICE published new guidance recommending endoscopic variceal band ligation for primary prevention of bleeding.2 3 A subsequent change in local policy sees patients with grade 2 or 3 varices identified during elective upper GI (UGI) endoscopy offered endoscopic variceal band ligation routinely. We aimed was to assess the impact of this policy change on the rate of variceal haemorrhages.MethodsElectronic endoscopy records at Gloucestershire Hospitals NHS Foundation Trust were interrogated to identify procedures performed for variceal surveillance (VS) or UGI bleeding and where the diagnosis was variceal bleeding over two periods: Jan-May 2015 and Oct 2017 to Mar 2018.ResultsOf the 92 VS procedures performed in the first period, 53 had varices, of which 9 (17%) underwent prophylactic banding.Of the 246 VS procedures performed in the second period, 166 had varices, of which 52 (31.3%) underwent prophylactic banding.The proportionate number of variceal bleeds in the first and second period was 8.8% (n=10) and 6% (n=17) respectively.ConclusionsThe increase in prophylactic banding since the policy change appears to have reduced the proportionate number of variceal bleeds by 2.6%. This is seen alongside a significantly increased number of patients attending for VS, for unclear reasons. This could simply reflect the increasing burden of chronic liver disease.4 However, given the short interval period it could reflect an improvement in identifying patients suitable for variceal screening.ReferencesJairath V, et al. Acute variceal haemorrhage in the United Kingdom: patient characteristics, management and outcomes in a nationwide audit. Dig Liver Dis 2014;46:419–26.Tripathi D, et al. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut 2015;0:1–25.Cirrhosis in over 16s: assessment and management. NICE [NG50].Pimpin L, et al. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J Hepatol 2018;69(3):718–35.

Background There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. Methods Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn’s disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. Results Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. Conclusions The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

Most African populations are regularly exposed to biomass smoke, but knowledge of associated health implications is limited. This study aimed to investigate the association between oesophageal cancer (OC) and exposure to biomass smoke. This case-control study was conducted in Lusaka, Zambia. Cases were patients with endoscopically diagnosed OC, while controls were healthy volunteers. Questionnaires were used to collect lifestyle risk factors. Two sets of data were analysed; one with unmatched cases and controls and the other one with matching by age and sex. We enrolled 366 patients (131 cases and 235 controls). Among the cases, 50 (38%) were female and the median age was 56 years (IQR = 46–65 years). OC was significantly associated with domestic exposure to biomass smoke in univariate analysis (OR: 3.1; 95% CI: 1.7–5.6, p < 0.001) and after adjusting for potential confounders (OR: 2.1; 95% CI: 1.1–3.8, p = 0.017). Matched comparisons showed similar results for this association in univariate analysis (OR: 2.9; 95% CI: 1.5–5.8, p < 0.001) and using conditional logistic regression (OR: 2.8; 95% CI: 1.3–5.9, p = 0.005). Other risk factors found to be associated with OC were rural residence (OR: 2.3; 95% CI: 1.0–5.3, p = 0.004), lack of formal education (OR: 3.9; 95% CI: 1.5–9.9, p = 0.04) and living in poor housing (OR: 2.4; 95% CI: 1.1–5.6, p = 0.034). In conclusion, there is an association between OC and domestic exposure to biomass smoke and other lifestyle factors linked to low socio-economic status.

ObjectivePatients with colorectal cancer (CRC) often face diagnostic delays. Faecal immunochemical testing (FIT) was introduced across the South West (SW) of England in October 2022 to support referral triage. This study evaluates the impact of FIT on referral patterns, investigations, outcomes and service adaptation across the region.Design/methodsWe performed a retrospective service evaluation using secondary care data from nine National Health Service (NHS) Trusts in the SW. Data were collected for July 2019, 2022 and 2023, representing prepandemic, pre-FIT and post-FIT periods. Outcomes included referral characteristics, investigation pathways, waiting times and cancer detection rates (CDRs), stratified by the National Institute for Health and Care Excellence guideline (NG12 (2023)) compliance.Results10 140 records were analysed. In 2023, 87.0% of referrals included FIT. Compared to 2019, a greater proportion of patients were referred with an asymptomatic FIT ≥10 μg Hb/g (p<0.001) and fewer with traditional symptoms (p<0.001). Colonoscopy and clinic attendance fell (p=0.023 and p<0.001), with increased use of direct-to-test pathways (p<0.001). Total investigation volume was unchanged. The CDR rose from 4.1% (2019) to 4.7% (2023) but not significantly (p=0.266). Waiting times returned to prepandemic levels. Among non-NG12 compliant referrals, 48.6% still underwent colonoscopy, with modest CDRs (2.3%)—the clinical appropriateness of this was unclear. Asymptomatic FIT-positive patients aged >50 with FIT >100 μg Hb/g had a CDR of 7.1%.ConclusionFIT has been widely adopted in primary care, facilitating more efficient secondary care triage and helping restore diagnostic capacity. While NG12 (2023) non-compliant referrals yield fewer cancers, some high-risk groups (particularly asymptomatic FIT-positive patients) should not be excluded from investigation.