Incorporating Tissue-Specific Gene Expression Data to Improve Chemical-Disease Inference of in Silico Toxicogenomics Methods.

In silico toxicogenomics methods are resource- and time-efficient approaches for inferring chemical-protein-disease associations with potential mechanism information for exploring toxicological effects. However, current in silico toxicogenomics systems make inferences based on only chemical-protein interactions without considering tissue-specific gene/protein expressions. As a result, inferred diseases could be overpredicted with false positives. In this work, six tissue-specific expression datasets of genes and proteins were collected from the Expression Atlas. Genes were then categorized into high, medium, and low expression levels in a tissue- and dataset-specific manner. Subsequently, the tissue-specific expression datasets were incorporated into the chemical-protein-disease inference process of our ChemDIS system by filtering out relatively low-expressed genes. By incorporating tissue-specific gene/protein expression data, the enrichment rate for chemical-disease inference was largely improved with up to 62.26% improvement. A case study of melamine showed the ability of the proposed method to identify more specific disease terms that are consistent with the literature. A user-friendly user interface was implemented in the ChemDIS system. The methodology is expected to be useful for chemical-disease inference and can be implemented for other in silico toxicogenomics tools.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Induction of Thymus Atrophy and Disruption of Thymocyte Development by Fipronil through Dysregulation of IL-7-Associated Genes.

The susceptibility of the immune system to immunotoxic chemicals is evident, particularly in the thymus, a vital primary immune organ prone to atrophy due to exposure to toxicants. Fipronil (FPN), a widely used insecticide, is of concern due to its potential neurotoxicity, hepatotoxicity, and immunotoxicity. Our previous study showed that FPN disturbed the antigen-specific T-cell functionality in vivo. As T-cell lineage commitment and thymopoiesis are closely interconnected with the normal function of the T-cell-mediated immune responses, this study aims to further examine the toxic effects of FPN on thymocyte development. In this study, 4-week-old BALB/c mice received seven doses of FPN (1, 5, 10 mg/kg) by gavage. Thymus size, medulla/cortex ratio, total thymocyte counts, double-positive thymocyte population, and IL-7-positive cells decreased dose-dependently. IL-7 aids the differentiation of early T-cell precursors into mature T cells, and several essential genes contribute to the maturation of T cells in the thymus. Foxn1 ensures that the thymic microenvironment is suitable for the maturation of T-cell precursors. Lyl1 is involved in specifying lymphoid cells and maintaining T-cell development in the thymus. The c-Kit/SCF collaboration fosters a supportive thymic milieu to promote the formation of functional T cells. The expression of IL-7, IL-7R, c-Kit, SCF, Foxn1, and Lyl1 genes in the thymus was significantly diminished in FPN-treated groups with the concordance with the reduction of IL-7 signaling proteins (IL-7, IL-7R, c-KIT, SCF, LYL1, FOXO3A, and GABPA), suggesting that the dysregulation of T-cell lineage-related genes may contribute to the thymic atrophy induced by FPN. In addition, FPN disturbed the functionality of thymocytes with an increase of IL-4 and IFN-γ production and a decrease of IL-2 secretion after T-cell mitogen stimulation ex vivo. Collectively, FPN significantly deregulated genes related to T-cell progenitor differentiation, survival, and expansion, potentially leading to impaired thymopoiesis.

A novel multitask learning algorithm for tasks with distinct chemical space: zebrafish toxicity prediction as an example.

Data scarcity is one of the most critical issues impeding the development of prediction models for chemical effects. Multitask learning algorithms leveraging knowledge from relevant tasks showed potential for dealing with tasks with limited data. However, current multitask methods mainly focus on learning from datasets whose task labels are available for most of the training samples. Since datasets were generated for different purposes with distinct chemical spaces, the conventional multitask learning methods may not be suitable. This study presents a novel multitask learning method MTForestNet that can deal with data scarcity problems and learn from tasks with distinct chemical space. The MTForestNet consists of nodes of random forest classifiers organized in the form of a progressive network, where each node represents a random forest model learned from a specific task. To demonstrate the effectiveness of the MTForestNet, 48 zebrafish toxicity datasets were collected and utilized as an example. Among them, two tasks are very different from other tasks with only 1.3% common chemicals shared with other tasks. In an independent test, MTForestNet with a high area under the receiver operating characteristic curve (AUC) value of 0.911 provided superior performance over compared single-task and multitask methods. The overall toxicity derived from the developed models of zebrafish toxicity is well correlated with the experimentally determined overall toxicity. In addition, the outputs from the developed models of zebrafish toxicity can be utilized as features to boost the prediction of developmental toxicity. The developed models are effective for predicting zebrafish toxicity and the proposed MTForestNet is expected to be useful for tasks with distinct chemical space that can be applied in other tasks.Scieific contributionA novel multitask learning algorithm MTForestNet was proposed to address the challenges of developing models using datasets with distinct chemical space that is a common issue of cheminformatics tasks. As an example, zebrafish toxicity prediction models were developed using the proposed MTForestNet which provide superior performance over conventional single-task and multitask learning methods. In addition, the developed zebrafish toxicity prediction models can reduce animal testing.

Impact of Fruit and Vegetable Enzyme Supplementation on Aerobic Performance and Lactate Response in Older Adults Following High-Intensity Interval Exercise Through Exergaming: Randomized Experimental Matched-Pair Study.

Background: Exercise offers substantial health benefits but can induce oxidative stress and inflammation, especially in high-intensity formats such as high-intensity interval exercise (HIIE). Exergaming has become an effective, enjoyable fitness tool for all ages, particularly older adults. Enzyme supplements may enhance exercise performance by improving lactate metabolism and reducing oxidative stress. Objective: This study investigates the efficacy of fruit and vegetable enzyme supplementation in modulating fatigue and enhancing aerobic capacity in older adults following HIIE through exergaming. Methods: The study recruited 16 older adult female participants and allocated them into 2 distinct groups (enzyme and placebo) based on their pretest lactate levels. This division used pairwise grouping to guarantee comparability between the groups, ensuring the integrity of the results. They engaged in HIIE using Nintendo Switch Ring Fit Adventure, performing 8 sets of 20 seconds of maximum effort exercise interspersed with 30 seconds of rest, totaling 370 seconds of exercise. Key metrics assessed included blood lactate levels, heart rate, rating of perceived exertion, and training impulse. Participants in the enzyme group were administered a fruit and vegetable enzyme supplement at a dosage of 30 mL twice daily over a period of 14 days. Results: The enzyme group showed significantly lower blood lactate levels compared to the placebo group, notably after the fourth (mean 4.29, SD 0.67 vs mean 6.34, SD 1.17 mmol/L; P=.001) and eighth (mean 5.84, SD 0.63 vs mean 8.20, SD 1.15 mmol/L; P<.001) exercise sessions. This trend continued at 5 minutes (mean 6.85, SD 0.82 vs mean 8.60, SD 1.13 mmol/L; P=.003) and 10 minutes (mean 5.91, SD 1.16 vs mean 8.21, SD 1.27 mmol/L; P=.002) after exercise. Although both groups exceeded 85% of their estimated maximum heart rate during the exercise, enzyme supplementation did not markedly affect the perceived intensity or effort. Conclusions: The study indicates that fruit and vegetable enzyme supplementation can significantly reduce blood lactate levels in older adults following HIIE through exergaming. This suggests a potential role for these enzymes in modulating lactate production or clearance during and after high-intensity exercise. These findings have implications for developing targeted interventions to enhance exercise tolerance and recovery in older adults.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

SLC10A1 rs2296651 variant (S267F mutation) predicts biochemical traits, hepatitis B virus infection susceptibility and the risk of gallstone disease.

Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1's versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

BACKGROUND/AIMS: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. METHODS: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. RESULTS: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Liver and atherosclerotic risks of patients with cryptogenic steatotic liver disease.

BACKGROUND AND AIMS: In 2023, a new nomenclature of "metabolic associated steatotic liver disease" (MASLD) has emerged by incorporating cardio-metabolic criteria to redefine "non-alcoholic fatty liver disease" (NAFLD). Among steatotic liver disease (SLD), those having no known causes and without any one of cardio-metabolic criteria are deemed to have cryptogenic SLD. This study aims to compare the liver and atherosclerotic risks between MASLD and cryptogenic SLD patients. APPROACH: We analyzed participants with liver ultrasound data from the Taiwan Bio-Bank cohort, excluding those with positive HBsAg, positive anti-HCV, or "frequent drinker". MASLD involves hepatic steatosis and any of five cardiometabolic risk factors, whereas cryptogenic SLD features hepatic steatosis without these risk factors. Liver fibrosis severity was assessed by using NAFLD fibrosis score (NFS), while atherosclerosis was determined by carotid plaques on duplex ultrasound. RESULTS: Among 17,595 subjects (age 55.47 ± 10.41; males 31.8%), 7538 participants (42.8%) had SLD, comprising 96.5% of MASLD and 3.5% of cryptogenic SLD. Cryptogenic SLD patients are younger and had a lower percentage of male than those with MASLD. After propensity score matching for age and sex, patients with cryptogenic SLD exhibited milder glucose and lipid profiles, fewer carotid plaques, lower liver steatosis, inflammation, and fibrosis markers than those with MASLD. CONCLUSIONS: In this large population-based study, cryptogenic SLD, the excluded group, occupy only 3.5% in NAFLD patients. It has lower liver and atherosclerotic risks than MASLD, supporting its exclusion from NAFLD and justifying the rationale for the new disease name and diagnostic criteria of MASLD.

Fipronil disturbs the antigen-specific immune responses and GABAergic gene expression in the ovalbumin-immunized BALB/c mice.

BACKGROUND: Fipronil (FPN) is a broad-spectrum pesticide and commonly known as low toxicity to vertebrates. However, increasing evidence suggests that exposure to FPN might induce unexpected adverse effects in the liver, reproductive, and nervous systems. Until now, the influence of FPN on immune responses, especially T-cell responses has not been well examined. Our study is designed to investigate the immunotoxicity of FPN in ovalbumin (OVA)-sensitized mice. The mice were administered with FPN by oral gavage and immunized with OVA. Primary splenocytes were prepared to examine the viability and functionality of antigen-specific T cells ex vivo. The expression of T cell cytokines, upstream transcription factors, and GABAergic signaling genes was detected by qPCR. RESULTS: Intragastric administration of FPN (1-10 mg/kg) for 11 doses did not show any significant clinical symptoms. The viability of antigen-stimulated splenocytes, the production of IL-2, IL-4, and IFN-γ by OVA-specific T cells, and the serum levels of OVA-specific IgG1 and IgG2a were significantly increased in FPN-treated groups. The expression of the GABAergic signaling genes was notably altered by FPN. The GAD67 gene was significantly decreased, while the GABAR ß2 and GABAR δ were increased. CONCLUSION: FPN disturbed antigen-specific immune responses by affecting GABAergic genes in vivo. We propose that the immunotoxic effects of FPN may enhance antigen-specific immunity by dysregulation of the negative regulation of GABAergic signaling on T cell immunity.

Multitask learning for predicting pulmonary absorption of chemicals.

Pulmonary absorption is an important route for drug delivery and chemical exposure. To streamline the chemical assessment process for the reduction of animal experiments, several animal-free models were developed for pulmonary absorption research. While Calu-3 and Caco-2 cells and their derived computational models were used in estimating pulmonary permeability, the ex vivo isolated perfused lung (IPL) models are considered more clinically relevant measurements. However, the IPL experiments are resource-consuming making it infeasible for the large-scale screening of potential inhaled toxicants and drugs. In silico models are desirable for estimating pulmonary absorption. This study presented a novel machine learning method that employed an extratrees-based multitask learning approach to predict the IPL absorption rate constant (kaIPL) of various chemicals. The shared permeability knowledge was extracted by simultaneously learning three relevant tasks of Caco-2 and Calu-3 cell permeability and IPL absorption rate. Seven informative physicochemical descriptors were identified. A rigorous evaluation of the developed prediction model showed good performance with a high correlation between predictions and observations (r = 0.84) in the independent test dataset. Two case studies of inhalation drugs and respiratory sensitizers revealed the potential application of this model, which may serve as a valuable tool for predicting pulmonary absorption of chemicals.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Prevalence and clinical outcomes in subtypes of metabolic associated fatty liver disease.

BACKGROUND/PURPOSE: In 2020, metabolic Associated Fatty Liver Disease (MAFLD) was proposed to replace non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria. The prevalence and clinical outcomes of MAFLD subtypes remained unclear. METHODS: The participants from Taiwan bio-bank cohort were included. MAFLD was defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, diabetes mellitus (DM), or metabolic dysfunction. The patients with positive HBsAg or anti-HCV were considered as chronic HBV or HCV infection. NAFLD fibrosis score (NFS) > 0.676 plus fibrosis 4 (FIB-4) score > 2.67 was defined as advanced liver fibrosis. Atherosclerosis was diagnosed as having carotid plaques on duplex ultrasounds. The clinical outcomes were assessed among four subtypes of MAFLD including DM, obesity, chronic HBV infection, and chronic HCV infection. RESULTS: A total of 21,885 participants (mean age 55.34 ± 10.31; 35.69% males) were included in the final analysis. Among them, 38.83% were diagnosed with MAFLD. The prevalence of MAFLD was 66.95% in DM patients, 65.07% in obese participants, 33.74% in chronic HBV patients, and 30.23% in chronic HCV patients. Logistic regression analysis showed that the subtypes of DM and chronic HCV infection were associated with an increased risk of advanced liver fibrosis in MAFLD patients. Additionally, the subtypes of DM and lean were associated with an increased risk of atherosclerosis, but a decreased risk of atherosclerosis in the subtype of chronic HBV infection. CONCLUSION: This population-based study proves the concept that subtypes of MAFLD can help risk stratification of clinical outcomes.

Lower Repetition Induces Similar Postactivation Performance Enhancement to Repetition Maximum After a Single Set of Heavy-Resistance Exercise.

ABSTRACT: Chen, C-F, Chuang, C-Y, Wang, C-C, Liu, S-A, Chang, H-W, and Chan, K-H. Lower repetition induces similar postactivation performance enhancement to repetition maximum after a single set of heavy-resistance exercise. J Strength Cond Res XX(X): 000-000, 2023-The study was divided into 2 parts to investigate the acute postactivation performance enhancement (PAPE) responses to lower repetitions at the same load of 87% 1 repetition maximum (1RM) in the upper and lower body. In part 1, 14 athletes performed plyometric push-up (PPU) after the conditioning activity (CA) of bench press (BP). In part 2, 13 athletes performed a countermovement jump (CMJ) after the CA of parallel squat (PS). Subjects completed 3, 4, or 5 repetitions (trials CA-3, CA-4, or CA-5) of BP or PS in randomized and counterbalanced order. The velocity of each movement of the trial was recorded. The PPU or CMJ was tested every 2 minutes after the trial up to 12 minutes to assess the Post-Max and optimal individual PAPE time. The mean velocity of the last movement of BP in CA-5 was significantly lower than that in CA-3 (0.23 ± 0.06 vs. 0.28 ± 0.06 m·second -1 , p < 0.05), and the velocity of PS in CA-4 or CA-5 was significantly lower than that in CA-3 (0.53 ± 0.07 and 0.50 ± 0.05 vs. 0.57 ± 0.07 m·second -1 , p < 0.05). The peak force of PPU and jump height of CMJ at Post-Max in the 3 trials were significantly greater than those at Pre ( p < 0.05). There were no significant differences among trials in the optimal individual PAPE times in either part of the study. A single set of 87% 1RM resistance exercises with 3 or 4 repetitions in both the upper body and the lower body induces similar PAPE to repetition maximum.

The impact of transpancreatic precut sphincterotomy on the quality of endoscopic retrograde cholangiopancreatography in a low-volume setting.

BACKGROUND AND AIMS: Although quality improvement is crucial for ERCP, a low practice volume can pose challenges to achieving high-quality bile duct cannulation. Transpancreatic precut sphincterotomy (TPS) has been proven effective for advanced cannulation. However, existing data mainly come from skilled endoscopists in large medical centers. The impact of TPS on ERCP quality in a lower-volume setting deserves investigation. METHODS: Our hospital performs approximately 200 ERCPs annually, with 1 expert endoscopist performing approximately half of them and 3 nonexpert endoscopists sharing the remaining cases. TPS was started and became our predominant advanced cannulation technique in April 2016. We retrospectively reviewed ERCP cases 3 years before and after the introduction of TPS. The primary endpoints of the study were the differences in 2 ERCP quality indicators, the bile duct cannulation rate and the incidence of post-ERCP pancreatitis (PEP). RESULTS: A total of 701 ERCP cases with naïve papilla were analyzed, with 350 patients treated before the introduction of TPS and 351 patients treated afterward. The successful cannulation rate was significantly improved (before, 87.4%; after, 92.3%, P = .032), whereas the incidence of PEP decreased, but not significantly (before, 4.0%; after, 2.8%; P = .402). All endoscopists benefited from using TPS, with nonexperts demonstrating a significantly higher improvement in the cannulation rate (before, 85.5%; after, 93.1%; P = .019). CONCLUSIONS: TPS can effectively enhance the quality of ERCP irrespective of practice volume.