Epidemiology and Natural History of Elderly-onset Inflammatory Bowel Disease: Results From a Territory-wide Hong Kong IBD Registry.

BACKGROUND: Elderly-onset inflammatory bowel disease [IBD], defined as age ≥60 at diagnosis, is increasing worldwide. We aimed to compare clinical characteristics and natural history of elderly-onset IBD patients with those of adult-onset IBD patients. METHODS: Patients with a confirmed diagnosis of IBD from 1981 to 2016 were identified from a territory-wide Hong Kong IBD registry involving 13 hospitals. Demographics, comorbidities, clinical features, and outcomes of elderly-onset IBD patients were compared with those of adult-onset IBD patients. RESULTS: A total of 2413 patients were identified, of whom 270 [11.2%] had elderly-onset IBD. Median follow-up duration was 111 months (interquartile range [IQR]: 68-165 months). Ratio of ulcerative colitis [UC]: Crohn's disease [CD] was higher in elderly-onset IBD than in adult-onset IBD patients [3.82:1 vs 1.39:1; p <0.001]. Elderly-onset CD had less perianal involvement [5.4% vs 25.4%; p <0.001] than adult-onset CD. Elderly-onset IBD patients had significantly lower cumulative use of immunomodulators [p = 0.001] and biologics [p = 0.04]. Elderly-onset IBD was associated with higher risks of: cytomegalovirus colitis (odds ratio [OR]: 3.07; 95% confidence interval [CI] 1.92-4.89; p <0.001); herpes zoster [OR: 2.42; 95% CI 1.22-4.80; p = 0.12]; and all cancer development [hazard ratio: 2.97; 95% CI 1.84-4.79; p <0.001]. They also had increased number of overall hospitalisations [OR: 1.14; 95% CI 1.09-1.20; p <0.001], infections-related hospitalisation [OR: 1.87; 95% CI 1.47-2.38; p <0.001], and IBD-related hospitalisation [OR: 1.09; 95% CI 1.04- 1.15; p = 0.001] compared with adult-onset IBD patients. CONCLUSIONS: Elderly-onset IBD was associated with increased risk of infections and cancer development, and increased infection- and IBD-related hospitalisations. Specific therapeutic strategies to target this special population are needed.

Cancer risk and chemoprevention in Chinese inflammatory bowel disease patients: a population-based cohort study.

Background and aim: Role of 5-aminosalicylic acid (5-ASA), statin and aspirin in reducing cancer risks in inflammatory bowel disease (IBD) remains controversial. We aimed to examine chemo-preventive effects of these drugs in all cancers in IBD in population-based setting.Methods: IBD patients diagnosed between 2000 and 2016 were identified from the Hong Kong IBD Registry and followed from IBD diagnosis until first cancer occurrence. Primary outcome was cancer development ≥6 months after IBD diagnosis. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated with Cox proportional hazards model. Additional effects of statin and aspirin on chemoprevention were also assessed.Results: Amongst 2103 IBD patients (857 Crohn's disease, 1246 ulcerative colitis; mean age 40.0 ± 15.6; 60.3% male) with 16,856 person-years follow-up, 48 patients (2.3%) developed cancer. The 5-r, 10-r and 15-year (95% CI) cumulative incidence of cancer were 1% (0.6 - 1.5%), 2.8 (2.0 - 3.9%) and 4.8 (3.4 - 6.5%), respectively. Total 1891 (89.9%) and 222 (10.6%) patients have received one or more prescriptions of 5-ASA and statin respectively. In multivariable analysis adjusted for age, gender, smoking status, IBD type and use of other medications, use of 5-ASA or statin was not associated with a reduced risk of cancer development (5-ASA: aHR 1.22, 95% CI: 0.60-2.48, p = .593; statin: aHR 0.48, 95% CI: 0.14-1.59, p = .227). Adding aspirin was not associated with a lowered cancer risk (aHR 1.18, 95% CI: 0.32-4.35, p = .799).Conclusion: Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.Key summaryInflammatory bowel diseases (IBD) including Crohn's disease and ulcerative colitis are associated with increased risk of both intestinal and extra- intestinal cancers.Various medications including 5-aminosalicylate acid (5-ASA), statins and aspirin have been studied for their chemoprevention effects. However, most studies focused on colorectal cancer only and showed conflicting evidence. No studies so far looked at the effects of these medications on all cancer development in IBD.The 5-, 10- and 15-year (95% confidence interval) cumulative incidence of cancer in Chinese IBD patients were 1 (0.6-1.5%), 2.8 (2.0-3.9%) and 4.8 (3.4-6.5%), respectively.Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.

Stopping anti-tumour necrosis factor therapy in patients with perianal Crohn's disease.

BACKGROUND: Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy. AIM: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy. METHODS: Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method. RESULTS: After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months. CONCLUSIONS: More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.

Machine learning model to predict recurrent ulcer bleeding in patients with history of idiopathic gastroduodenal ulcer bleeding.

BACKGROUND: Patients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have an increased risk of recurring ulcer complications. AIM: To build a machine learning model to identify patients at high risk for recurrent ulcer bleeding. METHODS: Data from a retrospective cohort of 22 854 patients (training cohort) diagnosed with peptic ulcer disease in 2007-2016 were analysed to build a model (IPU-ML) to predict recurrent ulcer bleeding. We tested the IPU-ML in all patients with a diagnosis of gastrointestinal bleeding (n = 1265) in 2008-2015 from a different catchment population (independent validation cohort). Any co-morbid conditions which had occurred in >1% of study population were eligible as predictors. RESULTS: Recurrent ulcer bleeding developed in 4772 patients (19.5%) in the training cohort, during a median follow-up period of 2.7 years. IPU-ML model built on six parameters (age, baseline haemoglobin, and presence of gastric ulcer, gastrointestinal diseases, malignancies, and infections) identified patients with bleeding recurrence within 1 year with an area under the receiver operating characteristic curve (AUROC) of 0.648. When we set the IPU-ML cutoff value at 0.20, 27.5% of patients were classified as high risk for rebleeding with a sensitivity of 41.4%, specificity of 74.6%, and a negative predictive value of 91.1%. In the validation cohort, the IPU-ML identified patients with a recurrence ulcer bleeding within 1 year with an AUROC of 0.775, and 84.3% of overall accuracy. CONCLUSION: We developed a machine-learning model to identify those patients with a history of idiopathic gastroduodenal ulcer bleeding who are not at high risk for recurrent ulcer bleeding.

Significant Medical and Surgical Morbidity in Perianal Crohn's Disease: Results from a Territory-Wide Study.

BACKGROUND: The presence of perianal fistulas in Crohn's disease [CD] denotes increased disease aggressiveness. We studied the epidemiology and clinical outcomes of perianal CD [PCD] using the Hong Kong territory-wide IBD Registry [HKIBDR]. METHODS: Consecutive patients with PCD were identified from the HKIBDR, and disease characteristics, treatments, and outcomes were analysed. The risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS: Among 981 patients with CD with 10530 patient-years of follow-up, 283 [28.8%] had perianal involvement, of which 120 [42.4%] were as first presentation. The mean age at diagnosis of PCD was 29.1 years, and 78.8% were male. The median follow-up duration was 106 months (interquartile range [IQR]: 65-161 months]. Perianal fistula [84.8%] and perianal abscess [52.7%] were the two commonest forms. Male, younger age at diagnosis of CD, and penetrating phenotypes were associated with development of PCD in multivariate analysis. Of 242 patients with fistulizing PCD, 70 [29.2%] required ≥5 courses of antibiotics, and 98 [40.5%] had ≥2 surgical procedures. Nine patients required defunctioning surgery and 4 required proctectomy. Eighty-four patients [34.7%] received biologics. Cumulative probabilities for use of biologics were 4.7%, 5.8%, and 8.6% at 12 months, 36 months, and 96 months, respectively, while the probabilities for surgery were 67.2%, 71.6%, and 77.7%, respectively. Five mortalities were recorded, including 2 cases of anal cancer, 2 CD-related complications, and one case of pneumonia. CONCLUSION: Over 40% of CD patients presented with perianal disease at diagnosis. Patients with PCD had poor outcome, with young age of onset, multiple antibiotic use, and repeated surgery.

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 Crohn's 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.

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 Crohn's 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.

Low-dose azathioprine is effective in maintaining remission in steroid-dependent ulcerative colitis: results from a territory-wide Chinese population-based IBD registry.

BACKGROUND: Whether low-dose azathioprine (AZA) is effective in maintaining remission in patients with steroid-dependent ulcerative colitis (UC) remains unclear. We assessed the efficacy and safety of low-dose AZA in a Chinese population with UC. METHODS: We identified steroid-dependent UC patients in clinical remission on AZA maintenance therapy from a territory-wide IBD Registry. Standard- and low-dose AZA were defined as at least 2 mg/kg/day and less than 2 mg/kg/day, respectively. Relapse rates were analyzed by Kaplan-Meier analysis and compared using log-rank test. RESULTS: Among 1226 UC patients, 128 (53% male, median duration on AZA 44 months) were included. Median maintenance AZA dose was 1.3 mg/kg/day. 97.7% of the patients were on concomitant oral 5-aminosalicylic acid. Cumulative relapse-free rates in patients on standard-dose and low-dose AZA were 71.2%, 52.8% and 45.2%, and 71.8%, 55.3% and 46.2% at 12, 24 and 36 months, respectively (p = 0.871). Relapse rate within 12 months was higher in patients who withdrew compared with those who maintained on AZA (52.6% versus 29.4%; p = 0.045). Mean corpuscular volume increased after AZA therapy in both of the low-dose [median (interquartile range, IQR): 88.2 (81.4-92.2) versus 95.1 (90.1-100.9) fl, p < 0.001] and standard-dose subgroups [median (IQR) 86.8 (76.9-89.9) versus 94.7 (85.9-99.7) fl, p < 0.001]. Leukopenia occurred in 21.1% of the patients. Patients on standard dose had a higher risk for leukopenia than those on low-dose AZA [odds ratio (OR) 3.9, 95% CI 1.9-8.2, p < 0.001]. CONCLUSIONS: In the Chinese population, low-dose AZA is effective for maintaining remission in steroid-dependent UC patients. Standard-dose AZA was associated with more than threefold increased risk of leukopenia.

Natural History of Elderly-onset Ulcerative Colitis: Results from a Territory-wide Inflammatory Bowel Disease Registry.

BACKGROUND AND AIMS: Data on the natural history of elderly-onset ulcerative colitis [UC] are limited. We aimed to investigate clinical features and outcomes of patients with elderly-onset UC. METHODS: Patients with a confirmed diagnosis of UC between 1981 and 2013, from 13 hospitals within a territory-wide Hong Kong Inflammatory Bowel Disease Registry, were included. Clinical features and outcomes of elderly-onset patients, defined as age ≥ 60 years at diagnosis, were compared with those of non-elderly-onset disease [< 60 years at diagnosis]. RESULTS: We identified 1225 patients, of whom 12.8% [157/1225; 56.1% male] had elderly-onset UC. Median duration of follow-up was 11 years [interquartile range, 6-16 years]. Age-specific incidence of elderly-onset UC increased from 0.1 per 100000 persons before 1991 to 1.3 per 100000 persons after 2010. There were more ex-smokers [32.2% vs. 12.2%, p < 0.001] and higher proportion of comorbidities [p < 0.001] in elderly-onset than non-elderly-onset patients. Disease extent, corticosteroids, immunosuppressants use, and colectomy rates were similar between the two groups. Elderly-onset disease was an independent risk factor for cytomegalovirus infection [odds ratio 2.9, 95% confidence interval 1.6-5.2, p < 0.001]. More elderly-onset patients had Clostridium difficile infection [11.0% vs. 5.4%, p = 0.007], hospitalisation for UC exacerbation [50.6% vs. 41.8%, p = 0.037], colorectal cancer [3.2% vs. 0.9%, p = 0.033], all-cause mortality [7.0% vs. 1.0%, p < 0.001], and UC-related mortality [1.9% vs. 0.2%, p = 0.017] than non-elderly-onset patients. CONCLUSIONS: Elderly-onset UC patients are increasing in number. These patients have higher risk of opportunistic infections, hospitalisation, colorectal cancer, and mortality than non-elderly-onset patients. Management and therapeutic strategies in this special group need careful attention.

Non-alcoholic fatty liver disease: an expanding problem with low levels of awareness in Hong Kong.

BACKGROUND AND AIM: With the Westernization of the lifestyle and the rising prevalence of obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is an emerging health problem in the Asia-Pacific region. The purpose of this study was to determine the awareness of NAFLD among the general population in Hong Kong. METHODS: A random telephone survey was conducted from September 2007 to January 2008 using a structured multiple-choice questionnaire. Subjects were Hong Kong residents aged 18 or above who spoke Cantonese. RESULTS: In the first phase of the telephone survey, 521 subjects were interviewed and the results showed that as high as 83% of respondents had never come across the term 'NAFLD'. Upon completion of the second phase telephone survey, a total of 508 respondents who had heard of NAFLD were successfully interviewed. Of the 508 respondents, nearly half of them (42%) expressed no idea about the prevalence of NAFLD in Hong Kong. About half of respondents (47%) knew nothing about the clinical presentation of NAFLD. The majority of them (78%) had a misconception that blood tests could provide a definite diagnosis of NAFLD. Smoking, hepatitis B carriage and a past history of hepatitis A infection were cited as risk factors of NAFLD by 52%, 57% and 42% of respondents, respectively. Of the 508 respondents who had heard of NAFLD, most of them perceived that their knowledge of NAFLD was either inadequate (46%) or highly inadequate (35%). CONCLUSION: This survey revealed an inadequate knowledge of NAFLD among the general population in Hong Kong.

Use of strontium isotopes to identify buried water main leakage into groundwater in a highly urbanized coastal area.

Previous studies indicate that the local aquifer systems in the Mid-Levels, a highly urbanized coastal area in Hong Kong, have commonly been affected by leakage from water mains. The identification of leakage locations was done by conventional water quality parameters including major and trace elements. However, these parameters may lead to ambiguous results and fail to identify leakage locations especially where the leakage is from drinking water mains because the chemical composition of drinking water is similar to that of natural groundwater. In this study, natural groundwater, seepage in the developed spaces, leakage from water mains, and parent aquifer materials were measured for strontium isotope (87Sr/86Sr) compositions to explore the feasibility of using these ratios to better constrain the seepage sources. The results show that the 87Sr/86Sr ratios of natural groundwater and leakage from water mains are distinctly different and thus, they can provide additional information on the sources of seepage in developed spaces. A classification system based on the aqueous 87Sr/86Sr ratio is proposed for seepage source identification.

Heavy metal and trace element distributions in groundwater in natural slopes and highly urbanized spaces in Mid-Levels area, Hong Kong.

The lower slope of the Mid-Levels area, Hong Kong, is one the most heavily urbanized coastal areas in the world. A comprehensive groundwater heavy metal and trace element study was conducted in the Mid-Levels area aiming to investigate the impacts of urbanization on the aqueous distributions of these chemicals. Groundwater samples were collected in the upper natural slopes and the lower highly urbanized spaces in the area in different seasons, and analyzed for heavy metal and trace element contents. Compared to the results from natural slopes, groundwater samples in the developed spaces did not exhibit significant elevated levels in Zn, Cr, Cu, Cd, Pb and Fe, which are commonly found in stormwater. On the other hand, the samples were found to have elevated contents in Mn, V, Co and Mo, minor stormwater-related heavy metals, suggesting that stormwater drains may be leaking to some extent. However, the results suggested that the vadose zone could remove many of the heavy metals, protecting groundwater from being contaminated seriously. Statistical analysis suggested that a certain amount of Mn and Co was likely to be re-mobilized from natural soils due to the changes in local redox conditions, while Mn, V, Co and Mo may also be derived from steel corrosion as a result of prolonged submergence. Besides, the average B concentration in the developed spaces was about eight times higher than that in the natural slopes, indicating the presence of sewage. The mean Se concentration in the developed spaces was about 100 times higher than that in the natural slopes. About 40% of samples in the developed spaces contained Se level higher than the drinking water guideline value proposed by the World Health Organization. Se was found to be positively correlated with B and SO4(2-) (R = 0.534 and 0.631, respectively), suggesting that Se may also be related to leakage from sewage pipes. Part of the Sr may come from leakage of flushing water and/or sewage as Sr was strongly correlated with Cl- (R = 0.929). According to the measured results, deep groundwater samples collected from piezometers (> 10 m in depth) in the urbanized spaces appeared to be virtually free from any anthropogenic contaminations. This study may shed important light on the identification and evaluation of leakage from service pipes in a particular area based on aqueous distributions of heavy metals and trace elements. Moreover, the above findings may be instructional for other coastal cities with a similar level of urban development to understand the potential threats to their groundwater resources.

Normal colon transit time in healthy Chinese adults in Hong Kong.

BACKGROUND AND AIM: Colon transit study with radio-opaque markers is helpful in the evaluation of chronic constipation. Normal reference values, based on radio-opaque markers, have not been reported from Chinese adults in Hong Kong. METHODS: Fifty-one healthy Chinese (27 men, age 42 +/- 12 years) were enrolled through a newspaper advertisement. They were requested to fill in detailed dietary records and a gastrointestinal symptom questionnaire. Each subject swallowed, under supervision, a total of three Sitzmarks capsules, one capsule at the same time on each of day 1, 2 and 3. Abdominal films were taken on days 4 and 7, also at the same time of the day. Total and segmental transit times were calculated using Metcalf's method. RESULTS: The upper limit of normal total colonic transit time (CTT) was 62 h, while right, left and rectosigmoid CTT were 16 h, 31 h and 32 h, respectively. Women of age 18-35 years had a longer rectosigmoid and total CTT compared with their male counterparts (mean total CTT: 39 h vs 18 h, P = 0.05). The CTT appeared to be unaffected by the usual dietary components. CONCLUSION: A single normal reference value for CTT appeared to be applicable to Chinese adults in Hong Kong, irrespective of age, sex and dietary content. However, young Chinese women (age 18-35 years) appeared to have longer total and rectosigmoid CTT.