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  1. Lim SZ, Chua EW
    Front Pharmacol, 2018;9:1107.
    PMID: 30349479 DOI: 10.3389/fphar.2018.01107
    Azathioprine and 6-mercaptopurine, often referred to as thiopurine compounds, are commonly used in the management of inflammatory bowel disease. However, patients receiving these drugs are prone to developing adverse drug reactions or therapeutic resistance. Achieving predefined levels of two major thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, is a long-standing clinical practice in ensuring therapeutic efficacy; however, their correlation with treatment response is sometimes unclear. Various genetic markers have also been used to aid the identification of patients who are thiopurine-sensitive or refractory. The recent discovery of novel Asian-specific DNA variants, namely those in the NUDT15 gene, and their link to thiopurine toxicity, have led clinicians and scientists to revisit the utility of Caucasian biomarkers for Asian individuals with inflammatory bowel disease. In this review, we explore the limitations associated with the current methods used for therapeutic monitoring of thiopurine metabolites and how the recent discovery of ethnicity-specific genetic markers can complement thiopurine metabolites measurement in formulating a strategy for more accurate prediction of thiopurine response. We also discuss the challenges in thiopurine therapy, alongside the current strategies used in patients with reduced thiopurine response. The review is concluded with suggestions for future work aiming at using a more comprehensive approach to optimize the efficacy of thiopurine compounds in inflammatory bowel disease.
  2. Chuah KH, Cheong SY, Lim SZ, Mahadeva S
    J Dig Dis, 2022 Jan 20.
    PMID: 35050547 DOI: 10.1111/1751-2980.13082
    OBJECTIVE: Functional gastrointestinal disorders (FGIDs) are known to have a significant impact on patients' quality of life and lead to a greater healthcare burden. In this study we aimed to investigate whether this healthcare burden differs among various types of FGIDs in secondary care.

    METHODS: A retrospective study of consecutive adults with luminal gastrointestinal (GI) diseases in a secondary healthcare gastroenterology clinic was conducted. The frequency of FGIDs and differences in healthcare utilization among different types of FGIDs were explored.

    RESULTS: Among 1206 patients with luminal GI disease, 442 (36.7%) had FGIDs. FGIDs patients were older (67 y vs 62 y, P 

  3. Chuah KH, Hian WX, Lim SZ, Beh KH, Mahadeva S
    J Dig Dis, 2023 Mar;24(3):194-202.
    PMID: 37200005 DOI: 10.1111/1751-2980.13189
    OBJECTIVE: To explore the factors associated with small intestinal bacterial overgrowth (SIBO), and to further evaluate the impact of SIBO on irritable bowel syndrome (IBS) in terms of symptom severity and health-related quality of life (HRQoL).

    METHODS: A cross-sectional study of consecutive adult patients who underwent glucose hydrogen breath test was conducted. Factors associated with SIBO were evaluated. Symptom severity and HRQoL of IBS patients with and without SIBO were compared. The independent factors associated with severe IBS were explored.

    RESULTS: A total of 160 patients were included (median age 40 years, males 31.3%). IBS was present among 53.8% of subjects, with 33.8% having diarrhea-predominant IBS (IBS-D). SIBO was diagnosed in 22.5% of the study population. Patients with SIBO were more commonly diagnosed with IBS-D than those without (50.0% vs 29.0%, P = 0.019). Severe IBS was associated with SIBO (36.4% vs 15.6%, P = 0.043). SIBO was associated with poorer HRQoL (Euroqol five-dimensional utility score: 0.73 vs 0.80, P = 0.024). SIBO (44.4% vs 20.6%, P = 0.043), anxiety (77.8% vs. 39.7%, P = 0.004), and depression (50.0% vs 19.1%, P = 0.011) were associated with severe IBS in the univariate analysis. However, SIBO was the only independent factor associated with severe IBS in the multivariate analysis (adjusted odds ratio 3.83, 95% confidence interval CI 1.02-14.34, P = 0.046).

    CONCLUSIONS: There was a significant association between IBS-D and SIBO. The coexistence of SIBO had a significant negative impact on IBS patients.

  4. Chuah KH, Black CJ, Tee V, Lim SZ, Hian WX, Sahran NF, et al.
    Aliment Pharmacol Ther, 2023 Jul;58(2):168-174.
    PMID: 37259882 DOI: 10.1111/apt.17567
    BACKGROUND: The prevalence of irritable bowel syndrome (IBS) is now known to be similar in various geographical regions, but there has been no study directly comparing characteristics of patients with IBS between populations.

    AIMS: To evaluate clinical and psychological differences between adults with IBS seen in secondary care in the United Kingdom (UK) and Malaysia.

    METHODS: Age- and sex-matched patients with IBS from a single centre in the UK (Leeds) and two centres in Malaysia (Kuala Lumpur and Kota Bharu), who fulfilled Rome III criteria, were recruited prospectively. Demographic characteristics and gastrointestinal and psychological symptoms were compared between both groups.

    RESULTS: A total of 266 (133 UK and 133 Malaysian) age- and sex-matched patients with Rome III IBS were recruited (mean age: 45.1 years Malaysia, vs. 46.5 years UK; 57.9% female). UK patients were more likely to consume alcohol than Malaysian patients (54.1% vs. 10.5%, p 

  5. Chuah KH, Wong MS, Tan PO, Lim SZ, Beh KH, Chong SCS, et al.
    Dig Dis Sci, 2021 Aug 21.
    PMID: 34417923 DOI: 10.1007/s10620-021-07227-4
    INTRODUCTION: Small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), but its' association with other functional gastrointestinal disorders (FGIDs) is less certain. This study aimed to explore SIBO in a multi-racial Asian population with various FGIDs compared to non-FGID controls.

    METHODOLOGY: Consecutive Asian adults with Rome III diagnosed common FGIDs (functional dyspepsia/FD, IBS and functional constipation/FC) and non-FGID controls were subjected to glucose breath testing, with hydrogen (H2) and methane (CH4) levels determined.

    RESULTS: A total of 244 participants (FGIDs n = 186, controls n = 58, median age 45 years, males 36%, Malay ethnicity 76%) were recruited. FGIDs had a higher prevalence trend of SIBO compared to controls (16% FGIDs vs. 10% controls, p = 0.278) with 14% in FD, 18% in IBS and 17% in FC. Compared to controls, SIBO was associated with diarrhoea-predominant IBS (IBS-D) (24% vs. 10%, P = 0.050) but not with other types of FGIDs. IBS-D remained an independent predictor of SIBO (OR = 2.864, 95% CI 1.160-7.071, p = 0.023) but not PPI usage nor history of diabetes (both p > 0.050) at multivariate analysis. Compared to controls, SIBO in IBS-D was associated with an elevated H2 level (≥ 20 ppm from baseline) (18% vs. 3%, p = 0.017), but not CH4 levels (≥ 10 ppm) (9% vs. 7%, p = 0.493). In addition, no difference was found in the prevalence of methane-positive SIBO between chronic constipation (constipation-predominant IBS and FC) compared to controls (9% vs. 7%, P = 0.466).

    CONCLUSION: SIBO is prevalent amongst multi-ethnic Asian adults with and without FGIDs. Amongst various FGIDs, only IBS-D is significantly associated with SIBO.

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