Use of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus infection and severe renal impairment.

BACKGROUND/AIMS: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. METHODS: We prospectively recruited patients with Child's A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017-2018 to receive GLE/PIB treatment. RESULTS: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. CONCLUSION: GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

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.

Switching to peginterferon for chronic hepatitis B patients with hepatitis B e antigen seroconversion on entecavir - A prospective study.

Nucleos(t)ide analogues (NA) are effective in suppressing hepatitis B virus (HBV) replication, but most patients require long-term treatment. This study aimed to investigate switching to peginterferon as a strategy to stop NA. Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who developed HBeAg seroconversion during NA treatment were studied. All patients received open-label peginterferon alfa-2a 180 µg/wk for 48 weeks, and NA was stopped at week 4 of peginterferon treatment. The primary endpoint was sustained response, which was defined as negative HBeAg, positive anti-HBe and HBV DNA <2000 IU/mL at week 72. Other secondary endpoints including HBsAg loss at week 72 were also studied. Forty-one patients treated with entecavir for 56 ± 23 months were recruited. Sustained response was achieved in 30 patients (73%, 95% confidence interval 58%-84%). At week 72, 31 (76%) patients had HBeAg seroconversion, 56 (23%) patients had undetectable HBV DNA, 31 (76%) patients had normal ALT, and 6 patients (15%) had HBsAg loss. Baseline HBsAg level was the best predictor for both sustained response and HBsAg loss; the best HBsAg cut-off for sustained response was <1500 IU/mL and that for HBsAg loss was <500 IU/mL by receiver operating characteristic curve analysis. Twenty-two of 25 (88%) patients with baseline HBsAg <1500 IU/mL had sustained response. Five of 10 (50%) patients with baseline HBsAg <500 IU/mL developed HBsAg loss. Switching to peginterferon can be considered as a treatment option in NA-treated patients with HBeAg seroconversion, particularly among those with lower HBsAg levels.

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 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.

Factors associated with mucosal healing in patients with ulcerative colitis in clinical remission.

BACKGROUND: Mucosal healing (MH) has been associated with improved outcomes in ulcerative colitis but factors associated with MH are not well defined. METHODS: Consecutive patients with ulcerative colitis in clinical remission (Mayo symptomatic subscore = 0) who had at least 1 colonoscopy since diagnosis from 6 centers were included. For patients who had at least 2 colonoscopies during follow-up, each colonoscopy was reviewed to define whether they had early MH (Mayo endoscopic subscore reduced to 0 within 3 yr of clinical remission). Factors associated with MH and early MH were determined using logistic regression. RESULTS: Two hundred thirty-seven patients with ulcerative colitis (mean age 50.39 ± 14.10 yr; 56.5% male) were included. Independent factors for MH were clinical remission >3 years (odds ratio [OR] 4.0; 95% confidence interval [CI], 1.2-13.1), mild/moderate mucosal inflammation (OR 3.3; 95% CI, 1.3-8.5), and immunosuppressant use (OR 4.6; 95% CI, 1.5-14.6). Among patients who had ≥2 of above factors, 74% achieved MH, whereas only 39% with <2 factors achieved MH (P < 0.001). Of patients in clinical remission <1 year, 1 to 3 years and >3 years, 30%, 45.9%, and 62.9% achieved MH, respectively. Immunosuppressant therapy was associated with early MH (P = 0.025). In multivariate analysis, patients with previous mild inflammation were more likely to achieve early MH than those with moderate/severe inflammation (OR 2.8; 95% CI, 1.2-6.2). CONCLUSIONS: A longer disease remission, previous less severe mucosal inflammation, and immunosuppressant use are associated with MH. Severity of mucosal inflammation and use of immunosuppressant are also associated with early MH.

Use of biologics for inflammatory bowel disease in Hong Kong: consensus statement.

UNLABELLED: OBJECTIVE; With the increasing use of biologics in patients with inflammatory bowel disease, the Hong Kong IBD Society developed a set of consensus statements intended to serve as local recommendations for clinicians about the appropriate use of biologics for treating inflammatory bowel disease. PARTICIPANTS: The consensus meeting was held on 9 July 2011 in Hong Kong. Draft consensus statements were developed by core members of the Hong Kong IBD Society, including local gastroenterologists and colorectal surgeons experienced in managing patients with inflammatory bowel disease. EVIDENCE: Published literature and conference proceedings on the use of biologics in management of inflammatory bowel disease, and guidelines and consensus issued by different international and regional societies on recommendations for biologics in inflammatory bowel disease patients were reviewed. CONSENSUS PROCESS: Four core members of the consensus group drafted 19 consensus statements through the modified Delphi process. The statements were first circulated among a clinical expert panel of 15 members for review and comments, and were finalised at the consensus meeting through a voting session. A consensus statement was accepted if at least 80% of the participants voted "accepted completely or "accepted with some reservation". CONCLUSIONS: Nineteen consensus statements about inflammatory bowel disease were generated by the clinical expert panel meeting. The statements were divided into four parts which covered: (1) epidemiology of the disease in Hong Kong; (2) treatment of the disease with biologics; (3) screening and contra-indications pertaining to biologics; and (4) patient monitoring after use of biologics. The current statements are the first to describe the appropriate use of biologics in the management of inflammatory bowel disease in Hong Kong, with an aim to provide guidance for local clinical practice.

Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1.

BACKGROUND AND AIMS: Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. METHODS: Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800-1200 mg of ribavirin daily plus either 180 mg of pegylated alpha-interferon-2a or 1.5 mg/kg pegylated alpha-interferon-2b weekly for 48 weeks. Their responses to treatments were compared. RESULTS: The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200,000 IU/mL or less were independent predictors for better SVR in this cohort. CONCLUSION: Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.