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.

Territory-wide population-based study of chronic hepatitis C infection and implications for hepatitis elimination in Hong Kong.

BACKGROUND: To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030. METHODS: From January 2005 to March 2017, patients who were tested positive for anti-HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed. RESULTS: A total of 11 309 anti-HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV-infected patients were ageing (median age 59). The all-cause mortality rate increased from 26.2 to 54.8 per 1000 person-years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg-IFN/RBV) but only 10.8% had received interferon-free direct-acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg-IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P = 0.005) and death (1.7% vs 23.8%, P < 0.001). CONCLUSION: Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg-IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation.

Direct health-care cost utilization in Hong Kong inflammatory bowel disease patients in the initial 2 years following diagnosis.

BACKGROUND AND AIM: There are scanty data on the health-care utilization from Asia where the incidence of inflammatory bowel disease (IBD) is rising rapidly. We aim to determine the direct health-care costs in the first 2 years of diagnosis in an IBD cohort from Hong Kong and the factors associated with high cost outliers. METHODS: This is a retrospective cohort study that included patients newly diagnosed with IBD in a territory-wide IBD registry. Patients' clinical information, hospitalization records, investigations, and IBD treatments were retrieved for up to 2 years following diagnosis of IBD. RESULTS: Four hundred and thirty-five newly diagnosed IBD patients were included: 198 with Crohn's disease and 237 with ulcerative colitis. Total direct medical expenditure for this cohort 2 years after the IBD diagnosis was $7 072 710: hospitalizations (33%), 5-aminosalicylic acid (23%), imaging and endoscopy (17%), outpatient visits (10%), surgery (8%), and biologics (6%). Mean direct medical costs per patient-year were significantly higher for Crohn's disease ($9918) than ulcerative colitis ($6634; P, 0.001). The total direct health-care cost decreased significantly after transition to the second year (P < 0.01). High cost (> 90th percentile) outliers were associated with surgery (OR 7.1, 95% CI 2.9-17.2) and low hemoglobin on presentation (OR 0.83, 95% CI 0.70-0.96). CONCLUSIONS: Hospitalization and 5-aminosalicylic acid usage accounted for 56% of total direct medical costs in the first 2 years of our newly diagnosed IBD patients. Direct health-care costs were higher in the first year compared with the second year of diagnosis. Surgery and low hemoglobin on presentation were associated with high cost outliers.

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.

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.

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.

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.

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.