Whitney Tang

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

Objective The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. Design 442 incident cases (186 Crohns disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. Results In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. Conclusions This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

Dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients

Summary. Epidemiological studies have shown a lower prevalence of tardive dyskinesia (TD) among Chinese psychiatric patients compared to Caucasian and Black patient populations. It has been hypothesized that pharmacogenetic factors may underlie this cross-cultural difference. Due to the important implications of the dopamine D3 receptor gene (DRD3) in motor control, we investigated the frequency of polymorphic serine (ser) to glycine (gly) substitution of the gene DRD3 in Chinese schizophrenic patients. The sample size consisted of 65 patients with TD and 66 without TD. Patients were assessed for the severity of TD, the presence of akathisia and parkinsonian symptoms and were subsequently genotyped. We found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia in Chinese patients with schizophrenia.

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia

BACKGROUND & AIMS The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohns and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohns disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. CONCLUSIONS In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes.

Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome

Objective Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. Design Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. Results Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. Conclusions In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. Trial registration number NCT02570477

Epidemiology of Inflammatory Bowel Disease from 1981 to 2014: Results from a Territory-Wide Population-Based Registry in Hong Kong

Background:Incidence of inflammatory bowel disease (IBD) is increasing in Asia, but population-based prevalence data are limited. This study examined IBD incidence and prevalence based on results of a territory-wide IBD registry in Hong Kong. Methods:We collected data on 2575 patients with IBD (1541 ulcerative colitis [UC], 983 Crohns disease [CD], 51 IBD unclassified) from 1981 to 2014 using hospital and territory-wide administrative coding system. Prevalence and incidence, disease phenotype, surgery, and mortality were analyzed. Results:Adjusted prevalence of IBD, UC, CD, and IBD unclassified per 100,000 individuals in 2014 were 44.0, 24.5, 18.6, and 0.9, respectively. Age-adjusted incidence of IBD per 100,000 individuals increased from 0.10 (95% confidence interval, 0.06–0.16) in 1985 to 3.12 (95% confidence interval, 2.88–3.38) in 2014. UC:CD incidence ratio reduced from 8.9 to 1.0 over 30 years (P < 0.001). A family history of IBD was reported in 3.0% of patients. Stricturing or penetrating disease was found in 41% and perianal disease in 25% of patients with CD. 5-aminosalicylate use was common in UC (96%) and CD (89%). Cumulative rates of surgery for CD were 20.3% at 1 year and 25.7% at 5 years, and the corresponding rates for UC were 1.8% and 2.1%, respectively. Mortality for CD and UC was not significantly different from the general population. Conclusions:In a population-based study in Hong Kong, prevalence of IBD is lower than in the west although comparable to that of other East Asian countries. Complicated CD is common. Overall mortality remains low in Asians with IBD.

Performance of Interferon-gamma Release Assay for Tuberculosis Screening in Inflammatory Bowel Disease Patients

Background:Screening for latent tuberculosis (TB) is mandatory in inflammatory bowel disease (IBD) before starting anti–tumor necrosis factor therapy. Data on the utility of screening tests in populations with moderate background risk of TB are limited. This study aims to evaluate the performance of interferon-gamma release assay (IGRA) with QuantiFERON-TB Gold in IBD patients in a TB endemic region. Methods:Two hundred sixty-eight consecutive adult IBD patients and 234 healthy controls were prospectively recruited. Detailed clinical history, chest x-ray findings, and IGRA results were documented for all individuals. The IGRA positive rates between IBD patients, with or without immunosuppressant, and healthy controls were compared. Results:The IGRA result was positive in 21.9% of IBD patients and 19.2% of healthy controls (P = 0.535). IBD patients on immunosuppressive therapy had a significantly lower IGRA positive rate (13.0% versus 29.6%; P = 0.002) compared with immunosuppressant-naive IBD patients. This difference seemed to be most prominent for patients taking azathioprine (11.8% versus 27.3%, P = 0.006). Conclusions:IGRA results are negatively impacted by immunosuppressive therapy. Current guidelines suggesting TB screening before anti–tumor necrosis factor therapy may be inadequate in patients already on immunosuppressive drugs. Latent TB testing seems best performed before the initiation of immunosuppressive therapies in IBD patients.

Prevalence and correlates of depression in Chinese elderly patients with pneumoconiosis

Recent literature suggests that patients with pneumoconiosis may be at higher risk of developing psychiatric problems, particularly depressive illness. There are no published data on depressive disorders in elderly patients with pneumoconiosis. The aim of this study was to evaluate the prevalence and correlates of depressive disorders in a community sample of elderly Chinese patients with pneumoconiosis in Hong Kong. Two hundred and one patients with pneumoconiosis were randomly selected from the case register of the Pneumoconiosis Compensation Fund Board of Hong Kong. A psychiatrist conducted a structured clinical interview to diagnose depressive disorders according to the Diagnostic Statistical Manual for Mental Disorders, Version IV criteria. Nineteen (9.5%) patients had depressive illness. Univariate logistic regression revealed that the number of comorbid conditions, and the scores on the Lubben Social Network Scale (LSNS) and Instrumental Activities of Daily Living (IADL) were significant predictors of depressive disorders. Multivariate logistic regression analysis found that IADL and LSNS scores were the only independent predictors of depressive disorders. In conclusion, depressive disorders were common and associated with poorer functional ability and social support in patients with pneumoconiosis.

Cancer Risk in 2621 Chinese Patients with Inflammatory Bowel Disease: A Population-based Cohort Study

Background: Studies on cancer risk in inflammatory bowel disease (IBD) have yielded inconsistent results. We conducted a population-based study to determine the risk of cancer in patients with Crohns disease (CD) and ulcerative colitis (UC). Methods: Using a territory-wide IBD registry in Hong Kong, we identified 2621 patients with IBD and no history of cancer from 1990 to 2016. We followed them from diagnosis until either September 2016, cancer development, proctocolectomy, or death. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. Results: Of 2621 patients with IBD (1108 CD; 1603 UC; median age, 49 yr; 59.5% men) followed for 26,234 person-years, 88 patients developed cancer after IBD diagnosis. Patients with CD had an increased risk of anorectal cancers (SIR 4.11; 95% confidence interval (CI), 1.84–9.14) and hematological cancers (SIR 3.86, 95% CI, 1.61–9.27) including leukemia (SIR 5.98; 95% CI, 1.93–18.54). Nonmelanoma skin cancer was significantly increased in both CD and UC (CD: SIR 13.88; 95% CI, 1.95–98.51; UC: SIR 9.05; 95% CI, 2.26–36.19). Patients with CD had a higher risk of renal-cell carcinoma (SIR 6.89; 95% CI, 2.22–21.37), and patients with UC had a higher risk of prostate cancer (SIR 2.47; 95% CI, 1.24–4.95). Conclusions: In a population-based study, Chinese patients with CD are at an increased risk of anorectal cancers and hematological cancers compared with the general population. A higher risk of nonmelanoma skin cancer was also observed in CD and UC. Cancer surveillance should be considered.

78 Incidence and Phenotype of Inflammatory Bowel Disease From 13 Countries in Asia-Pacific: Results From the Asia-Pacific Crohn's and Colitis Epidemiologic Study 2011-2013

Incidence and Phenotype of Inflammatory Bowel Disease From 13 Countries in Asia-Pacific: Results From the Asia-Pacific Crohns and Colitis Epidemiologic Study 2011-2013 Siew C. Ng, Gilaad Kaplan, Rupa Banerjee, Shu-Chen Wei, Whitney Tang, Zhirong Zeng, Min-hu Chen, Hong Yang, H. Janaka de Silva, Madunil A Niriella, David E. Ong, KhoonLin Ling, Ida Hilmi, Pises Pisespongsa, Satimai Aniwan, Julajak Limsrivilai, Murdani Abdullah, Vui Heng Chong, Qian Cao, Yinglei Miao, Arlinking K. Ong-Go, Sally Bell, Olga Niewiadomski, Michael A. Kamm, Ka Kei Ng, Hon Ho Yu, Yu-Fang Wang, Qin Ouyang, Khean Lee Goh, Hung-Hsin Lin, Wei-Chen Lin, Kaichun Wu, Marcellus Simadibrata, Francis K. Chan, Joseph Sung

Population Density and Risk of Inflammatory Bowel Disease: A Prospective Population-Based Study in 13 Countries or Regions in Asia-Pacific

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn’s disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43–1.57). India (9.31; 95% CI: 8.38–10.31) and China (3.64; 95% CI, 2.97–4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01–4.76]) and CD (IRR: 3.28; 95% CI: 1.83–9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10–5.16) and UC (IRR: 2.63; 95% CI: 1.2–5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91–0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05–1.24) was observed for CD incidence in China. This study received IRB approval. CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.