Navigating the complex terrain of hepatitis B virus reactivation in the era of Bruton tyrosine kinase inhibitors.

In this editorial, we offer a summary of the risk associated with hepatitis B reactivation (HBVr) in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase (BTK) inhibitors, with insights derived from current studies. Furthermore, we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments. This framework is essential for identifying those at increased risk of HBVr, enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.

Comparisons of traditional electrocardiographic criteria for left and right ventricular hypertrophy in young Asian women: The CHIEF heart study.

The performance of electrocardiographic (ECG) voltage criteria to identify left and right ventricular hypertrophy (LVH and RVH) in young Asian female adults have not been clarified so far.In a sample of 255 military young female adults, aged 25.2 years on average, echocardiographic LVH was respectively defined as the left ventricular mass (LVM) indexed by body surface area (BSA) (≥88 g/m) and by height (≥41 g/m), and RVH was defined as anterior right ventricular wall thickness >5.2 mm. The performance of ECG voltage criteria for the echocardiographic LVH and RVH were assessed by area under curve (AUC) of receiver operating characteristic (ROC) curve to estimate sensitivity and specificity.For the Sokolow-Lyon (the maximum of SV1 or SV2 + RV5 or RV6) and Cornell (RaVL + SV3) voltage criteria with the LVM/BSA ≥88 g/m, the AUC of ROC curves were 0.66 (95% confidence intervals [CI]: 0.52-0.81, P = .039) and 0.61 (95% CI: 0.44-0.77, P = .18), respectively. For these 2 ECG voltage criteria with the LVM/height ≥41 g/m, the AUC of ROC curves were 0.64 (95% CI: 0.52-0.75, P = 0.11) and 0.73 (95% CI: 0.61-0.85, P = 0.0074), respectively. The best cut-off points selected for the Sokolow-Lyon and Cornell voltage criteria with echocardiographic LVH in young Asian females were 26 mm and 6 mm, respectively. In contrast, all the AUC of ROC curves were less than 0.60 and not significant according to the Sokolow-Lyon (the maximum of RV1 + SV5 or V6) and Myers' voltage criteria (eg, the voltage of R wave in V1 and the ratios of R/S in V1, V5 and V6) with echocardiographic RVH.There was a suggestion that the ECG voltage criteria to screen the presence of LVH should be adjusted for the young Asian female adults, and with regard to RVH, the ECG voltage criteria were found ineffective.

Association of electrocardiographic left and right ventricular hypertrophy with physical fitness of military males: The CHIEF study.

AIM: To investigate the association of electrocardiographic (ECG) left and/or right ventricular hypertrophy (LVH and RVH) with physical fitness of military males. METHODS: We used a military cohort of 2587 males, who were on average 29.1 years of age, from the cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) study in Taiwan for the analysis. Isolated ECG-LVH (n = 779) was diagnosed by either the Sokolow-Lyon or Cornell voltage criteria. Isolated ECG-RVH (n = 234) was defined by either the Sokolow-Lyon or Myers et al. voltage criteria. Combined ECG-LVH/RVH (n = 140) was defined as those who met the voltage criteria for both LVH and RVH. The other ECGs were defined as unaffected (n = 1434). Physical fitness was evaluated by the upper and lower 16% exercise performance (beyond 1-standard deviation) in 3000-meter run, 2-minute sit-ups, and 2-minute push-ups. All procedures were standardized and monitored by unified computerized scoring systems. A multiple logistic regression was used to determine the relationship. RESULTS: Compared with unaffected participants, those with an isolated ECG-LVH were tended to have a better 3000-meter run performance (odds ratio (OR) and 95% confidence intervals: 1.22 [0.99-1.50], p-value = 0.064) after adjusting for age, service specialty, body mass index, mean blood pressure, smoking status, alcohol intake, hemoglobin level, and exercise frequency. By contrast, those with an isolated ECG-RVH were tended to have a worse 2-minute sit-up performance (OR: 1.46 [0.99-2.16], p-value = 0.054). CONCLUSION: Military males with ECG-LVH and/or ECG-RVH compared to unaffected participants may have diverse exercise performances. However, these observations narrowly failed to reach statistical significance.

Sex-Specific Association Between Serum Uric Acid and Elevated Alanine Aminotransferase in a Military Cohort: The CHIEF Study.

AIM: The study was conducted in order to examine the sex-specific association of serum uric acid (SUA) levels with elevated serum alanine aminotransferase (ALT) in a Taiwanese military cohort. METHODS: We made a cross-sectional examination of the sex-specific relationship using 6728 men and 766 women, aged 18-50 years from a large military cohort in Taiwan. SUA levels within the reference range (<7.0 mg/dL for men and <5.7 mg/dL for women respectively) were divided into quartiles and SUA levels greater than the upper reference limits were defined as hyperuricemia. Elevated ALT levels were defined as ≥40 U/L. Multivariate logistic regression analysis was performed to determine the association between each SUA category and elevated ALT levels in men and women, respectively. RESULTS: The prevalence of hyperuricemia and elevated ALT in men were 18.7% and 12.7%, respectively, and in women were 3.3% and 2.1%, respectively. As compared with the lowest SUA quartile, hyperuricemia was associated with elevated ALT in men (odds ratios (OR): 1.62, 95% confidence intervals (CI): 1.19-2.20) after controlling for age, service specialty, body mass index, metabolic syndrome components, current cigarette smoking, alcohol intake status, and weekly exercise times, but the associations for the other SUA quartiles were null. By contrast, the associations of hyperuricemia (OR: 0.81, 95% CI: 0.10-6.64) and the other SUA quartiles with elevated ALT were null in women. CONCLUSION: Our findings suggest that the relationship between each SUA level and elevated ALT may differ by sex among military young adults. The mechanism for the sex difference requires further investigations.

Sex-Specific Association between Metabolic Abnormalities and Elevated Alanine Aminotransferase Levels in a Military Cohort: The CHIEF Study.

The association of metabolic syndrome (MetS) components with elevated serum alanine aminotransferase (ALT) levels, a marker of hepatic injury, may differ between men and women. However, the sex-specific association in a military young population which has a low prevalence of MetS was unclear. We conducted a cross-sectional examination in 6738 men and 766 women, aged 18-50 years, from the cardiorespiratory fitness study in armed forces (CHIEF) in eastern Taiwan. The components of MetS were defined according to the updated International Diabetes Federation (IDF) ethnic criteria for Asians. Elevated ALT levels were defined as ≥40 U/L for both sexes and ≥30 U/L for women alternatively. Multivariate logistic regression analysis was performed to determine the sex-specific association between MetS components and elevated ALT. The prevalence of MetS and elevated ALT in men were 11.9% and 12.7% respectively, and in women were 3.5%, and 3.8% respectively. In men, high-density lipoprotein < 40 mg/dL, blood pressures ≥ 130/85 mmHg, serum triglycerides ≥ 150 mg/dL, and waist size ≥ 90 cm were associated with elevated ALT (odds ratios (OR) and 95% confidence intervals: 1.59 (1.34-1.90), 1.40 (1.19-1.65), 2.00 (1.68-2.39), and 1.68 (1.38-2.04); all p < 0.001); whereas in women, only fasting plasma glucose ≥ 100 mg/dL was associated with elevated ALT ≥ 40 U/L (OR: 7.59 (2.35-24.51), p = 0.001) and ALT ≥ 30 U/L (2.67 (0.89-7.95), p = 0.08). Our findings suggest that the relationship between metabolic abnormalities and elevated ALT may differ by sex, possibly due to the MetS more prevalent in young adult men than in women.

Chronic hepatitis B, nonalcoholic steatohepatitis and physical fitness of military males: CHIEF study.

AIM: To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. METHODS: We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B (n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis (n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected (n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. RESULTS: Chronic hepatitis B negatively correlated with 2-min push-up numbers (ß = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (ß = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (ß = -1.47, P = 0.040). CONCLUSION: Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism.

A comparison of Cornell and Sokolow-Lyon electrocardiographic criteria for left ventricular hypertrophy in a military male population in Taiwan: the Cardiorespiratory fitness and HospItalization Events in armed Forces study.

BACKGROUND: The Cornell and Sokolow-Lyon electrocardiography (ECG) criteria have been widely used for diagnosing left ventricular hypertrophy (LVH) in patients with hypertension. However, the correlations of these ECG criteria with LVH were rarely compared in military members who received rigorous training, particularly of the Asian male population. METHODS: We compared the Cornell voltage and product criteria with the Sokolow-Lyon criteria for the echocardiographic LVH in 539 military male members, ages 18-50 years and free of hypertension in the Cardiorespiratory fitness and HospItalization Events in armed Forces (CHIEF) study in Taiwan. Pearson's correlation coefficient was used to determine the association of each ECG criterion with the index of left ventricular mass (LVM, g)/height (m)2.7. The sensitivities and specificities were estimated using a receiver-operating characteristics (ROC) curve in relation to the echocardiographic LVH which was defined as LVM index ≥49 g/m2.7. RESULTS: The correlations of the Cornell voltage and product criteria (r=0.24 and 0.26 respectively, both P<0.0001) were stronger than that of the Sokolow-Lyon criteria (r=0.049 and 0.095, and P=0.26 and 0.03 respectively) with the LVM index. Similarly the performances of the Cornell voltage and product criteria for the echocardiographic LVH [area under curve (AUC): 0.66 and 0.68, both P<0.0001] were superior to that of the Sokolow-Lyon criteria (AUC: 0.54 and 0.53, both P>0.1) in the area under the ROC curve analysis. CONCLUSIONS: The Cornell ECG criteria for the echocardiographic LVH had better performance than the Sokolow-Lyon criteria in a young military male cohort in Taiwan.

Rationale and design of the cardiorespiratory fitness and hospitalization events in armed forces study in Eastern Taiwan.

AIM: To investigate the association between cardiorespiratory fitness and hospitalization events in a cohort of large voluntary arm forces in Taiwan. METHODS: The cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) is a retrospective cohort consisting of more than 4000 professional military members aged 18-50 years in Eastern Taiwan. All participants received history taking, physical examination, chest radiography, 12-lead electrocardiography, blood tests for cell counts and fasting glucose, lipid profiles, uric acid, renal function and liver function in the Hualien Armed Forces General Hospital during 2014. In addition, participants were required to undergo two indoor resistant exercise tests including 2-min push-up and 2-min sit-up, both scored by infrared sensing, and one outdoor endurance 3000-m none weight-bearing running test, the main indicator of cardiorespiratory fitness in the Military Physical Training and Testing Center in Eastern Taiwan in 2014. RESULTS: Hospitalization events for cardiovascular disease, acute kidney injury, rhabdomyolysis, severe infectious disease, acute psychiatric illness, diabetes, orthopedic surgery and mortality will be identified in the National Insurance Research Database for 10 years. CONCLUSION: CHIEF will be among the largest Eastern Asian armed forces cohort, in which physical status was strictly evaluated to follow up the hospitalization events for severe illness.

Genetic structural differences between responders and non-responders to interferon therapy for chronic hepatitis-B patients.

Interferon-alpha therapy has become a main stay of treatment for hepatitis-B patients. The sustained remission rates are around 30%, and the factors determining response are poorly defined. Our study aimed to search for the genetic differences between responder and non-responder patients. We have found 13 short tandem repeat markers (STR) that display different allele and/or genotype frequency between the two patient groups. Eleven out of 13 STR markers were selected to perform principal component analysis and hierarchical clustering. The study subjects could be further divided into six groups based on their genetic similarity, which correlated with the drug response rate. In conclusion, this pilot study has developed a new approach to identify genetic markers that allows us to predict the drug response in hepatitis B patients. Our study utilizing STR markers may provide an alternative approach to the utilized SNP markers in pharmacogenetic study.

Discovery of genetic difference between asthmatic children with high IgE level and normal IgE level by whole genome linkage disequilibrium mapping using 763 autosomal STR markers.

The genome-wide linkage disequilibrium screen for loci associated with genetic difference between allergic and nonallergic asthma was conducted with 763 autosomal STR markers and included 190 asthmatic children. Evidence for association with differences between the two forms of asthma was observed for 36 STR markers. Marker-to-marker synergetic effect and by simulation resampling tests revealed D5S2011, D6S305, and D9S286 were important loci in allergic asthma while D6S1574, D8S1769, and D19S226 were important in nonallergic asthma. Our results show strong genetic evidence that these markers play an important role in defining allergic and nonallergic asthma and provides important candidates of susceptible genes in these two categories of asthma. This study further shows that asthma is, indeed, a heterogeneous group of underlying diseases and, although with similar clinical phenotypes, may have different clinical severities, outcomes, and need more tailor-made management.