Short Message Service reminders reduce outpatient colonoscopy nonattendance rate: A randomized controlled study.

BACKGROUND AND AIM: Nonattendance of outpatient colonoscopy leads to inefficient use of health-care resources. We aimed to study the effectiveness of using Short Message Service (SMS) reminder prior in patients scheduled for outpatient colonoscopy on their nonattendance rate. METHODS: Patients who scheduled for an outpatient colonoscopy and had access of SMS were recruited from three clinics in Hong Kong. Patients were randomized to SMS group and standard care (SC) group. All patients were given a written appointment slip on the booking date. In addition, patients in the SMS group received an SMS reminder 7-10 days before their colonoscopy appointment. Patients' demographics, attendance, colonoscopy completion, and bowel preparation quality were recorded. Logistic regression was performed to identify predictors of nonattendance. RESULTS: From November 2013 to October 2019, a total of 2225 eligible patients were recruited. A total of 1079 patients were allocated to the SMS group and 1146 to the SC group. The nonattendance rate of patients in the SMS group was significantly lower than that in the SC group (8.9% vs 11.9%, P = 0.022). There were no significant differences in their baseline characteristics and colonoscopy completion rate and bowel preparation quality. A trend towards a higher rate of adequate bowel preparation was observed in the SMS group when compared with the SC group (69.9% vs 65.8%, P = 0.053). Independent predictors for nonattendance included younger age, underprivilege, and existing diabetes. CONCLUSIONS: An SMS reminder for outpatient colonoscopy is effective in reducing the nonattendance rate and may potentially improve the bowel preparation quality.

Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas.

OBJECTIVE: The risk associated with a family history of non-advanced adenoma (non-AA) is unknown. We determined the prevalence of colorectal neoplasms in subjects who have a first-degree relative (FDR) with non-AA compared with subjects who do not have an FDR with adenomas. DESIGN: In a blinded, cross-sectional study, consecutive subjects with newly diagnosed non-AA were identified from our colonoscopy database. 414 FDRs of subjects with non-AA (known as exposed FDRs; mean age 55.0±8.1 years) and 414 age and sex-matched FDRs of subjects with normal findings from colonoscopy (known as unexposed FDRs; mean age 55.2±7.8 years) underwent a colonoscopy from November 2015 to June 2018. One FDR per family was recruited. FDRs with a family history of colorectal cancer were excluded. The primary outcome was prevalence of advanced adenoma (AA). Secondary outcomes included prevalence of all adenomas and cancer. RESULTS: The prevalence of AA was 3.9% in exposed FDRs and 2.4% in unexposed FDRs (matched OR (mOR)=1.67; 95% CI 0.72 to 3.91; p=0.238 adjusted for proband sex and proband age). Exposed FDRs had a higher prevalence of any adenomas (29.2% vs 18.6%; mOR=1.87; 95% CI 1.32 to 2.66; p<0.001) and non-AA (25.4% vs 16.2%; mOR=1.91; 95% CI 1.32 to 2.76; p=0.001). A higher proportion of exposed FDRs than unexposed FDRs (4.3% vs 2.2%; adjusted mOR=2.44; 95% CI 1.01 to 5.86; p=0.047) had multiple adenomas. No cancer was detected in both groups. CONCLUSION: A positive family history of non-AA does not significantly increase the risk of clinically important colorectal neoplasia. The data support current guidelines which do not advocate earlier screening in individuals with a family history of non-AA. TRIAL REGISTRATION NUMBER: NCT0252172.

Low Risk of Variceal Bleeding in Patients With Cirrhosis After Variceal Screening Stratified by Liver/Spleen Stiffness.

We previously demonstrated the possible noninferiority of a screening strategy for varices guided by liver and spleen stiffness measurement (LSSM) compared to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. We now report the long-term outcome of the patients recruited in this trial for incident variceal bleeding and other hepatic events. This was a prospective follow-up study of a noninferiority, open-label, randomized controlled trial (NCT02024347) of 548 adult patients with known chronic liver diseases, radiological evidence of liver cirrhosis, and compensated liver function. The primary outcome of this prospective study was incident variceal bleeding confirmed with upper endoscopy. Between October 2013 and June 2016, 548 patients were randomized to an LSSM arm (n = 274) and a conventional arm (n = 274). Patients in both study arms were predominantly middle-aged men (mean age 59 years, male 68.9%) with viral hepatitis-related cirrhosis (85%). Upper endoscopy examination was performed in 127 (46.4%) patients in the LSSM arm and 263 (96.0%) in the conventional arm. During the follow-up period of 41.3 ± 12.6 months, 12/274 patients in the LSSM arm (4.4%) and 11/274 in the conventional arm (4.0%) developed incident variceal bleeding (log-rank test P = 0.724). The incident rates of hepatic events were also similar in both arms (P = 0.327). Conclusions: Patients with liver cirrhosis who had undergone LSSM-guided variceal screening were at similarly low risk of incident variceal bleeding in the future; patients with cirrhosis may first have LSSM measured to save up to half of the upper endoscopy examinations.

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.

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.

Correction to: Hepatitis B Surface Antigen Loss with Tenofovir Disoproxil Fumarate Plus Peginterferon Alfa-2a: Week 120 Analysis.

The original version of this article unfortunately contained affiliation and textual errors. This has been corrected with this erratum.

Contrasting Timing of Virological Relapse After Discontinuation of Tenofovir or Entecavir in Hepatitis B e Antigen-Negative Patients.

Stopping long-term nucleos(t)ide analogue therapy increases hepatitis B virus (HBV) surface antigen (HBsAg) loss rates in HBV e antigen (HBeAg)-negative patients. Viral rebound may induce immune responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as an HBV DNA load of >2000 IU/mL until week 12, and relapse occurred earlier in patients treated with tenofovir versus those treated with entecavir (median time, 6 vs 24 weeks; P < .0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.

A new screening strategy for varices by liver and spleen stiffness measurement (LSSM) in cirrhotic patients: A randomized trial.

BACKGROUND: Variceal bleeding is a common and life-threatening complication in patients with cirrhosis. Screening with upper endoscopy is recommended but is uncomfortable to patients. Non-invasive assessment with transient elastography for liver/spleen stiffness measurement (LSM and SSM) is accurate in detecting varices. AIMS: To test the hypothesis that a new screening strategy for varices guided by LSM/SSM results (LSSM-guided) is non-inferior to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. METHODS: This was a non-inferiority, open-label, randomized controlled trial. Adult patients with known chronic liver diseases, radiological evidence of cirrhosis and compensated liver function. The primary outcome was clinically significant varix diagnosed with upper endoscopy. RESULTS: Between October 2013 and June 2016, 548 patients were randomized to LSSM arm (n = 274) and conventional arm (n = 274) which formed the intention-to-test (ITT) population. Patients in both study arms were predominantly middle-aged men with viral hepatitis-related cirrhosis in 85% of the cases. In the ITT analysis, 11/274 participants in the LSSM arm (4.0%) and 16/274 in the conventional arm (5.8%) were found to have clinically significant varices. The difference between two groups was -1.8% (90% CI, -4.9% to -1.2%, P < .001). The absolute difference in the number of patients with clinically significant varices detected was 5/16 (31.3%) fewer in the LSSM arm. CONCLUSIONS: Non-inferiority of the LSSM-guided screening strategy to the convention approach cannot be excluded by this RCT. This approach should be further evaluated in a cohort of larger sample size with more clinically significant varices.

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.

Four-year Outcomes After Cessation of Tenofovir in Immune-tolerant Chronic Hepatitis B Patients.

GOALS: To study the long-term outcome after cessation of antiviral therapy in immune-tolerant patients. BACKGROUND: Experience in the treatment of immune-tolerant chronic hepatitis B is scanty. Some immune-tolerant patients may receive temporary antiviral therapy, such as for prevention of vertical transmission at pregnancy or prophylaxis for chemotherapy. STUDY: This was a follow-up study of a phase 2 trial at 2 centers. Immune-tolerant patients received tenofovir disoproxil fumarate and/or emtricitabine for 4 years and were followed for another 4 years after treatment cessation. Virological relapse was defined as hepatitis B virus (HBV) DNA>2000 IU/mL; clinical relapse was defined as HBV DNA>2000 IU/mL; and alanine aminotransferase (ALT)>2 times the upper limit of normal. RESULTS: In total, 20 patients stopped treatment and were followed up for 206±14 weeks. All patients developed virological relapse at posttreatment week 4 (HBV DNA, 7.07±1.45 log IU/mL). A total of 10 (50%) patients developed clinical relapse at 15±11 weeks (highest ALT, 1149 U/L). In total, 11 (55%) patients were restarted on antiviral therapy; 4 achieved complete HBV DNA suppression and 1 achieved hepatitis B e antigen (HBeAg) seroconversion. Among the 9 patients not restarted on therapy, 2 patients had HBeAg seroconversion with normal ALT and HBV DNA of 7.12 and 1.62 IU/mL, respectively. The remaining 7 untreated patients continued to have positive HBeAg, high HBV DNA, and normal ALT. CONCLUSIONS: Rapid virological relapse is universal and clinical relapse is common after stopping antiviral therapy in patients with immune-tolerant chronic hepatitis B. HBeAg seroconversion is rare regardless of treatment reinitiation.

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.

Hepatitis B Surface Antigen Loss with Tenofovir Disoproxil Fumarate Plus Peginterferon Alfa-2a: Week 120 Analysis.

BACKGROUND AND AIMS: Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120. METHODS: In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed. RESULTS: Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P < 0.001 for both) or group D (HBsAg loss: P = 0.002; HBsAg seroconversion: P < 0.001). CONCLUSIONS: The results of this analysis confirm the results from earlier time points which demonstrate the increased rate of HBsAg loss in patients treated with a finite course of PEG-IFN plus TDF compared with the rates in patients receiving either monotherapy.

Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study.

BACKGROUND & AIMS: The risk of colorectal neoplasms among siblings of patients with advanced adenomas is not clear. We determined the prevalence of advanced adenomas in the siblings of patients with advanced adenomas and compared it with that of siblings of individuals without these lesions. METHODS: In a blinded, cross-sectional study, colonoscopies were performed (from 2010 through 2014), at 2 hospitals in Hong Kong on 200 asymptomatic siblings of patients with advanced adenomas (exposed; mean age, 58.2 ± 6.3 years; adenomas ≥10 mm, high-grade dysplasia, villous, or tubulovillous) and 400 age- and sex-matched siblings of subjects with normal findings from colonoscopies and no family history of colorectal cancer (unexposed; mean age, 58.1 ± 6 years). We recruited 1 sibling per family. The primary outcome was prevalence of advanced adenomas. RESULTS: Baseline demographics (ie, aspirin use, smoking, body mass index, and metabolic diseases) did not differ significantly between exposed and unexposed individuals. The prevalence of advanced adenoma was 11.5% among the exposed subjects and 2.5% among the unexposed subjects (matched odds ratio [mOR] = 6.05; 95% confidence interval [CI]: 2.74-13.36; P < .001). The prevalence of adenomas ≥10 mm was higher among exposed than unexposed siblings (10.5% vs 1.8%; mOR = 8.59; 95% CI: 3.44-21.45; P < .001), as was the prevalence of villous adenomas (5.5% vs 1.3% in unexposed; mOR = 6.28; 95% CI: 2.02-19.53; P = .001) and all colorectal adenomas (39.0% vs 19.0% in unexposed; mOR = 3.29; 95% CI: 2.16-5.03; P < .001). Two cancers were detected in exposed siblings and none in unexposed siblings. CONCLUSIONS: In a cross-sectional study of subjects undergoing colonoscopy in Hong Kong, siblings of individuals with at least 1 advanced adenoma had a 6-fold increased odds of advanced adenoma compared with subjects who had a sibling with a screening colonoscopy with no identified neoplasia. ClinicalTrials.gov, Number: NCT01593098.

Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial. METHODS: In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72. RESULTS: At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups. CONCLUSIONS: A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.

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 Crohn's 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 Crohn's 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.

Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study.

BACKGROUND AND OBJECTIVE: The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated. METHODS: Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥ 2 years with undetectable HBV DNA levels on ≥ 3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000IU/mL). RESULT: 184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37-1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (± 0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=-0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p>0.05). CONCLUSIONS: Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.

Comparison of colonoscopic performance between medical and nurse endoscopists: a non-inferiority randomised controlled study in Asia.

OBJECTIVE: To test the hypothesis that trained nurse endoscopists are not inferior to medical endoscopists in finding adenomas during colonoscopy. DESIGN: This is a prospective, randomised, single-blind, non-inferiority study comparing nurses with medical endoscopists in performing screening colonoscopy. The nurse endoscopists had been trained according to the British Joint Advisory Group on GI Endoscopy curriculum and had completed at least 140 colonoscopic procedures prior to the study. The primary endpoint was the adenoma detection rate. Secondary endpoints included the caecal intubation rate, intubation time, complication rate, patient pain and satisfaction scores. RESULTS: We enrolled and analysed a total of 731 patients over a 15-month period. At least one adenoma was found in 159 (43.8%) of 363 patients by nurse endoscopists and 120 (32.7%) of 367 patients by medical endoscopists and a proportion difference of +11.1% compared with the medical endoscopists (95% CI 4.1% to 18.1%). The withdrawal time was, however, significantly longer among nurses (998 vs 575 s, p<0.001). After adjusting for differences in a regression analysis, colonoscopy by nurses was associated with a lower adenoma detection rate (OR 0.475: 95% CI 0.311 to 0.725). Nurse endoscopists had a lower caecal intubation rate (97.3% vs 100%), received better pain and satisfaction scores and had a high rate of patient acceptance. CONCLUSIONS: In this pragmatic trial, nurses can perform screening colonoscopy but require a longer procedural time to achieve a comparable adenoma detection rate as medical endoscopists. TRIAL REGISTRATION NUMBER: NCT01923155.

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 Crohn's 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.

Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA.

BACKGROUND & AIMS: Little is known about the benefit of antiviral therapy for hepatitis B e antigen (HBeAg)-positive patients with high viral load and normal levels of alanine aminotransferase. We evaluated the effects of single and combination therapies in immune-tolerant patients with chronic hepatitis B. METHODS: In a double-blind study, nucleos(t)ide-naïve patients with high levels of hepatitis B virus (HBV) DNA who were positive for HBeAg and had normal levels of alanine aminotransferase were randomly assigned to groups given either oral tenofovir disoproxil fumarate (TDF, 300 mg) and placebo (n = 64) or a combination of TDF (300 mg) and emtricitabine (200 mg, n = 62) for 192 weeks. The primary end point was proportion of patients with serum levels of HBV DNA <69 IU/mL at week 192. RESULTS: The study population (mean age was 33 years; 89% were Asian) was predominantly infected with HBV genotypes B and C (93%), 99% were HBeAg positive with a mean baseline level of HBV DNA of 8.41 log10 IU/mL. At week 192, 55% of patients (35 of 64) in the TDF+placebo group and 76% of patients (47 of 62) in the TDF+emtricitabine group had levels of HBV DNA <69 IU/mL (P = .016). No patients were found to have viral resistance to therapy. HBeAg seroconversion occurred in 3 patients (5%), all in the TDF+placebo group; no patient had loss of hepatitis B surface antigen. In multivariate analysis, female sex (odds ratio = 7.05; P = .002) and TDF+emtricitabine treatment (odds ratio = 3.9; P = .01) were associated with a favorable response. Both regimens were well tolerated. CONCLUSIONS: In HBeAg-positive patients with chronic HBV infection, high viral loads, normal levels of alanine aminotransferase, and therapy with the combination of TDF and emtricitabine provided better viral suppression than TDF alone, although rates of HBeAg seroconversion and hepatitis B surface antigen loss were low.

Randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection.

BACKGROUND AND AIMS: Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections. METHODS: This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e-antigen (HBeAg) positive. One hundred and forty-one patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV-DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events. RESULTS: The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV-DNA from baseline. Reductions in HBV-DNA were not significantly different, except the 1200 µg every 4 weeks albinterferon dose which was inferior compared with pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups. CONCLUSIONS: Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665).