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.

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.

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

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

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.

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.

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.

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.

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.

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.

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.

Canine diffuse large b-cell lymphoma downregulates the activity of CD8 + T-cells through tumor-derived extracellular vesicles.

BACKGROUND: Tumor-derived extracellular vesicles (EVs) have been proposed as the essential mediator between host immunity and cancer development. These EVs conduct cellular communication to facilitate tumor growth, enable invasion and metastasis, and shape the favorable tumor microenvironment. Lymphoma is one of the most common hematological malignancies in humans and dogs. Effective T-cell responses are required for the control of these malignancies. However, the immune crosstalk between CD8 + T-cells, which dominates anti-tumor responses, and canine lymphoma has rarely been described. METHODS: This study investigates the immune manipulating effects of EVs, produced from the clinical cases and cell line of canine B cell lymphoma, on CD8 + T-cells isolated from canine donors. RESULTS: Lymphoma-derived EVs lead to the apoptosis of CD8 + T-cells. Furthermore, EVs trigger the overexpression of CTLA-4 on CD8 + T-cells, which indicates that EV blockade could serve as a potential therapeutic strategy for lymphoma patients. Notably, EVs transform the CD8 + T-cells into regulatory phenotypes by upregulating their PD-1, PD-L1, and FoxP3 mRNA expression. The regulatory CD8 + T-cells secret the panel of inhibitory cytokines and angiogenic factors and thus create a pro-tumorigenic microenvironment. CONCLUSION: In summary, the current study demonstrated that the EVs derived from canine B cell lymphoma impaired the anti-tumor activity of CD8 + T-cells and manipulated the possible induction of regulatory CD8 + T-cells to fail the activation of host cellular immunity.

Erratum to 'Impact of HBV infection on clinical outcomes in patients with metabolic dysfunction-associated fatty liver disease' (JHEP Reports 5 [2023] 100836).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100836.].

The impact of concomitant hepatitis C virus infection on liver and cardiovascular risks in patients with metabolic-associated fatty liver disease.

BACKGROUND: Chronic hepatitis C virus (HCV)-infected patients with hepatic steatosis are excluded from the diagnosis of nonalcoholic fatty liver disease (NAFLD). The new name and diagnostic criteria of metabolic-associated fatty liver disease (MAFLD) were proposed in 2020 to replace the original term NAFLD. The clinical outcome of MAFLD patients with concomitant chronic HCV infection requires further investigation. METHODS: The participants from Taiwan bio-bank cohort were included. MAFLD is defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, type 2 diabetes, or metabolic dysfunction. The patients with positive anti-HCV were considered chronic HCV infections. The severity of liver fibrosis was determined using the fibrosis-4 index and NAFLD fibrosis score (NFS). The risk of cardiovascular disease (CVD) was assessed using intima-media thickness (IMT) or plaques of carotid duplex ultrasound. RESULTS: A total of 18 907 participants (age 55.79 ±â€…10.42; males 31.9%) were included for final analysis. The prevalence of MAFLD and chronic HCV infections were 39.2% and 2.6%, respectively. According to the status of MAFLD and chronic HCV infection, they were distributed to four groups: 'dual etiology group', 'MAFLD alone', 'HCV alone', and healthy controls. Compared with the 'MAFLD alone' group, the 'dual etiology' group had a lower frequency of the male sex, reduced levels of serum triglyceride, total cholesterol, and LDL; but overall older age, a higher percentage of hypertension history. In addition, they had higher levels of serum aspartate aminotransferase, fibrosis-4 index, and NFS; but no difference in levels of alanine aminotransferase, gamma-glutamyl transferase, fatty liver index, IMT, and the percentage of carotid plaques. Using binary logistic regression, chronic HCV infection was associated with more severe liver fibrosis, but not with carotid plaques in MAFLD patients. CONCLUSION: MAFLD patients with concomitant HCV infection, a specific phenotype of MAFLD may include a higher risk of advanced liver fibrosis, but a similar risk of atherosclerotic cardiovascular disease compared to those without.

Impact of HBV infection on clinical outcomes in patients with metabolic dysfunction-associated fatty liver disease.

Background & Aims: The new name and diagnostic criteria of metabolic-associated fatty liver disease (MAFLD) was proposed in 2020. Although chronic HBV infection has protective effects on lipid profiles and hepatic steatosis, the impact of chronic HBV infection on clinical outcomes of MAFLD requires further investigation. Methods: The participants from a Taiwan bio-bank cohort were included. MAFLD is defined as the presence of hepatic steatosis plus any of the following three conditions: overweight/obesity, type 2 diabetes mellitus, and metabolic dysfunction. The patients with positive glycated haemoglobin were considered as having chronic HBV infection. Atherosclerosis was determined as having carotid plaques on duplex ultrasound. Advanced liver fibrosis was defined as Fibrosis-4 >2.67. Based on the status of MAFLD and HBV infection, the participants were distributed into four groups: 'dual aetiology', 'MAFLD alone', 'HBV alone', and 'healthy controls'. Results: A total of 20,460 participants (age 55.51 ± 10.37; males 32.67%) were included for final analysis. The prevalence of MAFLD and chronic HBV infections were 38.8% and 10.3%, respectively. According to univariate analysis, 'HBV alone' group had lower levels of glycated haemoglobin, lipid profiles, and intima media thickness than healthy controls. The 'dual aetiology' group had lower levels of triglycerides, cholesterol, γ-glutamyl transferase, intima media thickness, and percentage of carotid plaques than 'MAFLD alone' group. Using binary logistic regression, chronic HBV infection increased the overall risk of advanced liver fibrosis; and had a lower probability of carotid plaques in MAFLD patients, but not in those without MAFLD. Conclusions: The large population-based study revealed chronic HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in patients with MAFLD. Impact and implications: Patients with metabolic-associated fatty liver disease can also be coinfected with chronic HBV. Concomitant HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in patients with MAFLD.

Machine learning for predicting chemical migration from food packaging materials to foods.

Food contact chemicals (FCCs) can migrate from packaging materials to food posing an issue of exposure to FCCs of toxicity concern. Compared to costly experiments, computational methods can be utilized to assess the migration potentials for various migration scenarios for further experimental investigation that can potentially accelerate the migration assessment. This study developed a nonlinear machine learning method utilizing chemical properties, material type, food type and temperature to predict chemical migration from package to food. Nine nonlinear algorithms were evaluated for their prediction performance. The ensemble model leveraging multiple algorithms provides state-of-the-art performance that is much better than previous linear regression models. The developed prediction models were subsequently applied to profile the migration potential of FCCs of high toxicity concern. The models are expected to be useful for accelerating the assessment of migration of FCCs from package to foods.

Predictors of Liver Dysfunction After Transhepatic Arterial Chemo-embolization in Hepatocellular Carcinoma Patients.

BACKGROUND AND AIMS: Although transhepatic arterial chemo-embolization (TACE) is beneficial for the survival of intermediate stage hepatocellular carcinoma (HCC) patients, its cost is the damage of liver reserve. Liver dysfunction is one of factors associated with TACE refractory status and poor prognosis. The study aims to determine the prevalence and predictors of liver dysfunction in HCC patients after TACE.. METHODS: Using the ASUS EMR search 3.0 system, the patients with discharge codes "HCC (C22.0)" plus "TACE" were collected since 2016 till 2021 in Taipei Tzu Chi Hospital. Liver reserve was determined by modified albumin-bilirubin (mALBI) grade. The liver dysfunction was defined as mALBI grade migration within 1-3 months after TACE.. RESULTS: A total of 220 HCC patients with 314 TACE were found in 5-year duration. Those with TACE-experienced tumors, incomplete laboratory data for mALBI grade and incorrect diagnosis coding were excluded. 91 HCC patients (62 male; mean age 65.86 ± 11.61 year-old) were recruited for final analysis. 10 (11%) patients with baseline mALBI grade 3 were excluded. The percentage of mALBI grade migration was 27.2% (22/81) after TACE. Binary logistic regression discovered "up-to-seven out" and "up-to-eleven out" were associated with mALBI grade migration after TACE. CONCLUSION: In this retrospective study, liver dysfunction occurred in 27.2% of HCC patients after TACE. "Up-to-seven out" and "up-to-eleven out" were predictors for liver dysfunction after TACE, suggesting early switch to systemic therapy to reduce the risk of liver dysfunction for HCC patients with high tumor burden.