Sofosbuvir/Ledipasvir in the Treatment of Chronic Hepatitis C - A Subgroup Analysis from A Nationwide Real-World HCV Registry Program (TACR) in Taiwan

( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.

Antiproliferative and Antitumorigenic Activity of Toona sinensis Leaf Extracts in Lung Adenocarcinoma

Chih-Jen Yang,Yu-Jung Huang,Cheng-Yuan Wang,Chuan-Sheng Wang,Pei-Hui Wang,Jen-Yu Hung,Tung-Heng Wang,Hseng-Kuang Hsu,Hurng-Wern Huang,S.P. Anand Kumar,Ming-Shyan Huang,Ching-Feng Weng 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.1

Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G1 peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G1 arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti–lung cancer drug.

Does the Fit of Managerial Ability with Firm Strategy Matters on Firm Performance

CHENG, Teng Yuan,LI, Yue-Qi,LIN, Yu-En,CHIH, Hsiang-Hsuan Korea Distribution Science Association 2020 The Journal of Asian Finance, Economics and Busine Vol.7 No.4

The study aims to answer why the previous studies find the positive or insignificant effect of the CEO's abilities on firm performance. Using 34,285 CEO-firm-year panel data from the U.S. publicly traded firms drawn from the BoardEx and EXECUXOMP database during from 1992 to 2014, the results show that the fit of the CEO's generality or specialist ability with firm strategy matters on firm performance and risk. This study computes a discrete STRATEGY composite measure to construct firm strategy types, such as Prospect or Defend and use CEOs' résumés to construct an index of general skills that are transferable across firms and industries. The results find that generalist CEOs are more suitable for prospectors than specialist CEOs. Firm performance is much better when specialist CEOs work for Defenders. Although the firm performance is better too for the generalist CEOs who fit for the Prospect strategy, the firm's risk is up too. The result suggests that firms need to consider their chosen business strategy to recruit and select CEOs Our findings provide direct evidence that the match between CEO's ability and the firm's strategy is crucial to firm performance and risk.

Experimental study of controllable MR-TLCD applied to the mitigation of structure vibration

Chih-Wen Cheng,Hsien Hua Lee,Yuan-Tzuo Luo 국제구조공학회 2015 Smart Structures and Systems, An International Jou Vol.15 No.6

MR-TLCD (Magneto-Rheological Tuned Liquid Column Damper) is a new developed vibration control device, which combines the traditional passive control property with active controllability advantage. Based on traditional TLCD governing equation, this study further considers MR-fluid viscosity in the equation and by transforming the non-linear damping term into an equivalent linear damping, a solution can be obtained. In order to find a countable set of parameters for the design of the MR-TLCD system and also to realize its applicability to structures, a series of experimental test were designed and carried out. The testing programs include the basic material properties of the MR-fluid, the damping ratio of a MR-TLCD and the dynamic responses for a frame structure equipped with the MR-TLCD system subjected to strong ground excitations. In both the analytical and experimental results of this study, it is found that the accurately tuned MR-TLCD system could effectively reduce the dynamic response of a structural system.

An Integration of Kano`s Model and Exit-Voice Theory: A Case Study

Yu Cheng Lee,Hsiu Yuan Hu,Tieh Min Yen,Chih Hung Tsai 한국품질경영학회 2009 The Asian Journal on Quality Vol.10 No.2

An Integration of Kano's Model and Exit-Voice Theory : A Case Study

Lee, Yu-Cheng,Hu, Hsiu-Yuan,Yen, Tieh-Min,Tsai, Chih-Hung The Korean Society for Quality Management 2009 The Asian Journal on Quality Vol.10 No.2

The purpose of this study was to examine overall customer satisfaction associated with medical service quality in Taiwan by integrated Kano's model and customer satisfaction index model. Another purpose was to confirmed nonlinear and asymmetric relationship of Customer Satisfaction and Quality Performance by the research outcome. By analyzing 1,100 patients or their family members, this study used the structural equation model (SEM) with AMOS software for data analysis. The results show that must-be attributes, one-dimensional attributes and attractive attributes had a direct effect on overall customer satisfaction, Surprisingly, overall customer satisfaction had positively influenced customer loyalty customer satisfaction had negatively influenced customer complaints. The study also found that customer complaints have direct effect on customer loyalty. Importantly, the study found out the must-be attributes, the attractive attributes and one-dimensional attributes increased, the level of overall customer satisfaction also increased. The customer satisfaction positively influences customer loyalty in medical service quality in Taiwan. The findings might reveal new insights for researchers dealing with quality of medical service and for hospital managers who devote resources exclusively to achieving highest possible levels of patient satisfaction.

Risk of Hepatitis B Virus (HBV) Reactivation in HBsAg-Negative, Anti-HBc-Negative Patients Receiving Rituximab for Autoimmune Diseases in HBV Endemic Areas

Lan Ting-Yuan,Lin Yen-Chun,Tseng Tai-Chung,Yang Hung-Chih,Kao Jui-Hung,Cheng Chiao-Feng,Lee Tai-Ju,Huang Shang-Chin,Lu Cheng-Hsun,Li Ko-Jen,Hsieh Song-Chou 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Background/Aims: Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods: From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions: In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

Laser Interference Lithography and Nanoimprint Techniques for Lower Reflection Transparent Conducting Oxide Hybrid Films

Ta-Hsin Chou,Kuei-Yuan Cheng,Chih-Chieh Su,Tien-Li Chang,Chih-Wei Hsieh,Jen-Hui Tsai 한국정밀공학회 2010 International Journal of Precision Engineering and Vol.11 No.4

The transparent conducting oxide (TCO) film is a significant component in flat panel display industry, applied for flexible display, e-paper, and touch panel. The TCO materials have high refractive index, so the phenomenon of high reflectance is the major issue and needs solved in present and future market. In this study, the structure and process of new lower reflection TCO hybrid film is introduced. The laser interference lithography and UV nanoimprint are combined for fabrication of sub-wavelength structures on PET film, then the tin-doped indium oxide (ITO) deposited on structures. Finally, the best result of this hybrid film is reflectance reduced to 3.3% at wavelength 550nm, just 13% of the original film, and the resistance of ITO layer is 1.05x10-3 Ω-cm. This result is useful for the TCO film applied in low reflection demand products in the future.

Effects of 5HT1A Activation on Gating Profile Following 5HT Depletion in Rats Lacking Social Attachment Since Weanling

Yueh-Ming Tai,Chih-Yuan Ko,Chen-Cheng Lin,Yu-Yue Wan,Jing-Yi Chung,Yia-Ping Liu 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.2

Objective Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. Methods Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. Results Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. Conclusion The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.

Interleaved DC-DC Converters with Partial Ripple Current Cancellation

Bor-Ren Lin,Huann-Keng Chiang,Chih-Yuan Cheng 전력전자학회 2012 JOURNAL OF POWER ELECTRONICS Vol.12 No.2

An interleaved PWM converter is proposed to implement the features of zero voltage switching (ZVS), load current sharing and ripple current reduction. The proposed converter includes two ZVS converters with a common clamp capacitor. With the shared capacitor, the charge balance of the two interleaved parts is automatically regulated under input voltage and load variations. The active-clamping circuit is used to realize the ZVS turn-on so that the switching losses on the power switches are reduced. The ZVS turn-on of all of the switching devices is achieved during the transition interval. The interleaved pulse-width modulation (PWM) operation will reduce the ripple current and the size of the input and output capacitors. The current double rectifier (CDR) is adopted in the secondary side to reduce output ripple current so that the sizes of the output chokes and capacitor are reduced. The circuit configuration, operation principles and design considerations are presented. Finally experimental results based on a 408W (24V/17A) prototype are provided to verify the effectiveness of the proposed converter.