Objective: To explore the differences in frequency and epidemiology of functional gastrointestinal disorders (FGIDs) in a primary care setting, and to examine the health-related quality of life (HRQOL) and healthcare utilization of FGID patients based on the Rome III and Rome IV criteria. Methods: A cross-sectional study of consecutive adults in a primary healthcare setting was conducted. Differences in epidemiology, and HRQOL of common FGIDs (functional dyspepsia [FD], irritable bowel syndrome [IBS], functional diarrhea, functional constipation [FC]) between the Rome III and IV criteria were explored. Results: Among a total of 1002 subjects recruited, the frequency of common FGIDs was 20.7% and 20.9% among subjects based on the Rome III and Rome IV criteria, respectively. The frequency of IBS reduced from 4.0% (Rome III) to 0.8% (Rome IV), while that of functional diarrhea increased from 1.2% (Rome III) to 3.3% (Rome IV). In contrast, there was no significant change in the frequency of FD (7.5% [Rome III] vs 7.6% [Rome IV]) and FC (10.5% [Rome III] vs 11.7% [Rome IV]). Most of the Rome III IBS subjects (52.5%, n = 21) who did not meet Rome IV IBS criteria, fulfilled the criteria for FC, functional diarrhea, FD, or overlap syndrome. Subjects with all FGIDs, regardless of criteria, had more healthcare utilization and lower HRQOL compared to non-FGID controls. Conclusions: The Rome IV criteria alter the frequency of IBS and functional diarrhea, but not FD and FC, when compared to the Rome III criteria. Regardless of criteria, FGIDs had a significant impact on healthcare burden and HRQOL.

Culture forms an integral aspect of environmental factors which influences disease presentation and clinical outcomes in functional gastrointestinal disorders (FGIDs). In this review, the role of culture in FGIDs in the East is briefly explored with regards to symptom presentation and diagnostic issues, lifestyle and cultural habits, epidemiology, and healthcare seeking behavior. In both functional dyspepsia and irritable bowel syndrome, symptom presentation and disease sub-typing in Asians are known to differ from their Western counterparts, possibly relating to cultural dietary practices and from cultural perception of symptoms. Dietary patterns, together with defecating practices are explored as factors contributing to a lower prevalence of constipation in the East. An urban-rural difference in the prevalence of FGIDs in Asia is attributed to a change in dietary patterns in rapidly developing urban communities, together with an increased level of psychological morbidity. Lastly, cultural attitudes towards traditional/local remedies, variation in healthcare systems, anxiety regarding organic disease, and religious practices have been shown to influence healthcare seeking behavior among FGID patients in the East.

Abbreviations: 95% CI, 95% confidence interval; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUROC, area under the receiver operating characteristic curve; BMI, body mass index; CK18, cytokeratin 18; F, fibrosis stage; FIB-4, fibrosis-4 index; HbA1c, glycated haemoglobin; HOMA, homeostatic model assessment of insulin resistance; MACK-3, combination of hoMa, Ast and CK18; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score; NASH, non-alcoholic steatohepatitis; NFS, NAFLD fibrosis score. Abstract Introduction: MACK-3 (combination of hoMa, Ast and CK18) was reported to be a good biomarker for the diagnosis of fibrotic non-alcoholic steatohepatitis (NASH). However, there is no external validation to date. Aim: To evaluate the accuracy of MACK-3 for the diagnosis of fibrotic NASH. Methodology: Consecutive adult non-alcoholic fatty liver disease (NAFLD) patients who had liver biopsy in a university hospital were included. MACK-3 was calculated using the online calculator using the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18). MACK-3 cut-offs ≤0.134 and ≥0.550 were used to predict absence and presence of fibrotic NASH, respectively. Histopathological examination of liver biopsy specimen was reported according to the NASH Clinical Research Network Scoring System. Results: Data for 196 subjects were analysed. MACK-3 was good for diagnosis of fibrotic NASH (area under receiver-operating characteristics curve [AUROC] 0.80), comparable to the Fibrosis-4 index (FIB4) and the NAFLD fibrosis score (NFS) and superior to the BARD score and CK18. MACK-3 was good for diagnosis of active NASH (AUROC 0.81) and was superior to other blood fibrosis tests. The overall accuracy, percentage of subjects in grey zone, sensitivity, specificity, positive predictive value and negative predictive value of MACK-3 for diagnosis of fibrotic NASH was 79.1%, 46.9%, 100%, 43.8%, 43.1% and 100%, respectively, while for diagnosis of active NASH was 90.0%, 39.3%, 84.2%, 81.4%, 88.9% and 74.5%, respectively. Conclusion: MACK-3 is promising as a non-invasive test for active NASH and fibrotic NASH and may be useful to identify patients who need more aggressive intervention. K E Y W O R D S active NASH, cytokeratin-18, fibrotic NASH, non-invasive test

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 < 0.001) with a higher proportion of women (61.8% vs 50.4%, P < 0.001) than those without FGIDs. Functional dyspepsia (FD) was the most common FGIDs (36.9%), followed by irritable bowel syndrome (IBS) (30.3%). A high healthcare burden (defined as over one GI endoscopy or imaging examination over 5 years, or one or more unscheduled visit to general practitioner or emergency department or hospitalization annually) was observed among 53.8% of the FGIDs patients. FD was associated with a high healthcare burden (high vs low burden: 43.7% vs 28.9%, P = 0.001) while IBS was associated with lower healthcare burden (high vs low burden: 25.2% vs 36.3%, P = 0.012). On multivariate analysis, only FD was significantly associated with high healthcare burden (adjusted odds ratio 1.996, 95% confidence interval 1.117-3.567, P = 0.020). Conclusion:Compared with other FGIDs, FD was the most common condition in secondary care, and it was associated with the greatest healthcare burden.

Background and aim The association between body mass index (BMI) and functional gastrointestinal disorders (FGIDs) has been inconsistent. We aimed to explore the association of BMI with FGIDs in a primary care setting to provide more data in this area. Methods A cross-sectional study of consecutive Asian adults attending a primary healthcare setting was conducted. This study was conducted in 2 phases: The association between BMI and common FGIDs (functional diarrhea/FD, irritable bowel syndrome/IBS, functional diarrhea and functional constipation/FC) was studied initially. The influence of anxiety and depression on BMI and FGIDs was additionally explored in phase 2. Results A total of 1002 subjects (median age 32 years, 65.4% females, 90.7% Malay ethnicity, 73.2% higher than secondary level education) were recruited between August 2019 to January 2020. The majority of subjects were obese (39.2%), and had central obesity (51.7%), while 6.1% had metabolic syndrome. The prevalence of FD, IBS, functional diarrhea and FC were 7.5% (n = 75), 4.0% (n = 40), 1.2% (n = 12) and 10.5% (n = 105) respectively, based on the Rome III criteria. Among individual FGIDs, FD subjects had more underweight adults (BMI<18.5kg/m2) compared to controls (13.3% vs 3.5%, P = 0.002) and being underweight remained as an independent association with FD [OR = 3.648 (95%CI 1.494–8.905), P = 0.004] at multi-variate analysis. There were no independent associations between BMI and other FGIDs. When psychological morbidity was additionally explored, anxiety (OR 2.032; 95%CI = 1.034–3.991, p = 0.040), but not depression, and a BMI<18.5kg/m2 (OR 3.231; 95%CI = 1.066–9.796, p = 0.038) were found to be independently associated with FD. Conclusions FD, but not other FGIDs, is associated with being underweight. This association is independent of the presence of anxiety.