Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study.

BACKGROUND: Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB). AIM: To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice. METHODS: This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors. RESULTS: During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45-4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03-1.42) and male sex (aSHR, 1.58; 95% CI, 1.04-2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4-year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%-1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%-2.0%). CONCLUSIONS: Severe flares with hepatic decompensation were observed in 1%-2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.

Physical Fitness and Inflammatory Bowel Disease Risk Among Children and Adolescents in Taiwan.

Importance: The incidence of inflammatory bowel disease (IBD) is increasing in newly industrialized countries but disease etiologies remain unclear. Objective: To investigate the association between physical fitness and subsequent IBD risk among children and adolescents in Taiwan. Design, Setting, and Participants: This nationwide cohort study was conducted between January 1, 2010, and December 31, 2018. Data sources included the Taiwan National Health Insurance Research Database, the National Student Fitness Tests Database, and the Air Quality Monitoring System Database. This study included students who were aged 10 years, completed physical fitness tests between grades 4 and 13, and had at least 1 year of follow-up. Data analysis was last performed on January 15, 2023. Exposures: Physical fitness tests included cardiorespiratory endurance (CE; number of minutes to complete an 800-m run), musculoskeletal endurance (ME; number of bent-leg curl-ups in 1 minute), musculoskeletal power (MP; standing broad jump distance), and flexibility fitness (FF; 2-leg sit-and-reach distance). Main Outcomes and Measures: Subsequent risk of IBD was compared among students based on physical fitness test results. Six-year cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. Performance was reported in quantiles, ranging from 1 (best) to 4 (poorest). Results: There were 4 552 866 students who completed physical fitness tests between grades 4 and 13; among these students, 1 393 641 were aged 10 years and were included in the analysis. Six-year cumulative incidence of IBD risk was lowest among students in the best-performing quantile of CE (quantile 1, 0.74% [95% CI, 0.63%-0.86%]; P < .001), ME (0.77% [0.65%-0.90%]; P < .001), and MP (0.81% [0.68%-0.93%]; P = .005) compared with students in quantiles 2 through 4, respectively; however, no association was observed for quantiles of FF. After adjusting for competing HRs for mortality and other confounders, better CE was inversely associated with IBD risk (adjusted HR, 0.36 [95% CI, 0.17-0.75]; P = .007). Other measures of physical fitness were not independently associated with IBD risk. Conclusions and Relevance: The results of this study suggest that CE was inversely associated with IBD risk among children and adolescents, but ME, MP, and FF were not independently associated with IBD risk. Future studies that explore the mechanisms are needed.

Association of Immunosuppressants with Mortality of Patients with Bullous Pemphigoid: A Nationwide Population-Based Cohort Study.

BACKGROUND: Bullous pemphigoid (BP) is a common autoimmune blistering skin disease with substantial mortality. OBJECTIVE: To identify whether the use of immunosuppressants was associated with reduced mortality in BP patients. METHODS: The data for this study were obtained from the National Health Insurance Research Database in Taiwan from January 1, 1997 to December 31, 2013. Those BP patients receiving any immunosuppressant for ≥28 days per month for 3 consecutive months were defined as the immunosuppressant cohort. In total, 452 BP patients on immunosuppressants were matched 1:4 by age, sex, propensity score of comorbidities, and use of tetracycline with 1,808 BP patients taking only corticosteroids. RESULTS: The immunosuppressant cohort had a significantly lower 5-year mortality rate than the corticosteroid cohort (0.57 vs. 0.67). In the multivariable regression analysis adjusted for covariates, the use of immunosuppressants significantly reduced the risk of mortality (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.68-0.90, p < 0.001). Hyperlipidemia also reduced risk of mortality. However, age, diabetes, renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, and dementia were significant risk factors for mortality. In the subgroup analysis, the risk of mortality decreased most substantially in those aged <70 years (HR: 0.45, 95% CI: 0.28-0.72). CONCLUSION: Immunosuppressant use was associated with a 22% reduced risk of BP mortality. The effects were more substantial in those aged <70 years, with a 55% reduced risk of mortality.

Association between dipeptidyl peptidase-4 inhibitors and risk of bullous pemphigoid in patients with type 2 diabetes: A population-based cohort study.

AIMS: Higher bullous pemphigoid (BP) risk has been reported to be associated with dipeptidyl peptidase 4 inhibitor (DPP4i). The aim of this study is to examine the association between BP risk and DPP4i treatment. METHODS: We conducted a nationwide cohort study based on the Taiwan National Health Insurance Database between 2000 and 2015. 124,619 diabetic patients who were receiving DPP4i therapy were matched 1: 1 with diabetic patients who had never received DPP4i by age, sex, duration of diabetes, insulin usage, and propensity score-matching of comorbidities. RESULTS: The 6-year cumulative incidence of BP in the DPP4i-treated cohort was significantly higher than that in the non-DPP4i group (0.74 per 1000 vs 0.38 per 1000, P = 0.001). Modified Cox regression analysis revealed that DPP4i treatment (HR: 2.15, 95% CI: 1.18-3.91, P = 0.01), age (HR: 1.06, P < 0.001), renal disease (HR: 2.32, P < 0.001), and metformin user (HR: 1.93, P = 0.006) were associated with increased BP risk. CONCLUSIONS: DPP4i users had a 2.2-fold increase in the risk of BP, and the risk was the highest in those with concomitant use of DPP4i and insulin.

Synthesis of amino core compounds of galactosyl phytosyl ceramide analogs for developing iNKT-cell inducers.

1-Aminophytosphingosine and 6-aminogalactosyl phytosphingosine were prepared in 61% and 40% yield libraries with 44 carboxylic acids showed that a 4-butylbenzoic acid-derived product exe, respectively. Glycosylation using benzoyl-protected lipid resulted in better a-selectivity for ceramide analogs, but the yield was less than that obtained with benzyl moieties. Screening the amide rted less cytotoxicity. These analogs were purified for validation of immunological potencies and the a-GalCer analog but not the sphingosine analog stimulated human iNKT cell population.