Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.

Objective Developing a new type of full-face respiratory protective mask for nuclear facility sites to enhance the sound transmission function and improve the facial adaptability. Methods Combined with feedback from on-site practical needs, this study utilized finite element simulation and ergonomic design methods to investigate the voice transmission units of full-face masks and the facial features of workers at key nuclear facilities. Based on the research results, a new full-face respiratory protection mask structure was designed. Results The optimized structure of passive thin film voice transmission unit significantly enhanced voice transmission efficiency, reducing average voice transmission loss by approximately 70% compared to the control group using thin plate units of equivalent thickness. The existing facial feature test panels insufficiently cover and unevenly classify the facial features of workers at key nuclear facilities. In this study, a specialized test panel based on measurement data achieved a total coverage of 98.5% with high distribution uniformity within each class, providing effective guidance for redesigning full-face mask structural parameters. In comparison to foreign products currently utilized in nuclear facilities, the newly designed full-face mask structure exhibited excellent tightness and structural safety and reliability, and can be cleaned, decontaminated, and reused. Conclusion The results of this study provide significant guidance for improving and optimizing full-face respiratory protection mask used at nuclear facilities, as well as promoting domestic production of high-quality full-face respiratory protection masks.

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.

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. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

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. Conclusions 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.