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.

A Hybrid Grey Model to Forecast the Annual Maximum Daily Rainfall

Yong-Jun Lin,Pin-Chan Lee,Kuo-Chen Ma,Chih-Chiang Chiu 대한토목학회 2019 KSCE JOURNAL OF CIVIL ENGINEERING Vol.23 No.11

This study proposes a hybrid grey model for forecasting annual maximum daily rainfall in order to determine long-term hydrological system trends. The proposed model uses an integral form of background value to improve accuracy, and applies two residual operators, the Fourier series and the exponential smoothing technique, to correct periodic and stochastic errors. The annual maximum daily rainfall measured by 5 stations around Taiwan are used to validation the proposed model. The performance of the proposed hybrid grey model is compared with those of the autoregressive integrated moving average (ARIMA) and artificial neural network (ANN) models. By evaluation of different indicators, it is shown that the proposed model outperforms both compared models. With more precise information, the proposed model will allow government officials and civil engineering-related industries to better prepare for heavy rainfall, averting potential disasters.

Clinical Outcomes and Cost-Effectiveness of Osteoporosis Screening With Dual-Energy X-ray Absorptiometry

Hsu Chiao-Lin,Wu Pin-Chieh,Yin Chun-Hao,Chen Chung-Hwan,Lee King-Teh,Lin Chih-Lung,Shi Hon-Yi 대한영상의학회 2023 Korean Journal of Radiology Vol.24 No.12

Objective: This study aimed to evaluate the clinical outcomes and cost-effectiveness of dual-energy X-ray absorptiometry (DXA) for osteoporosis screening. Materials and Methods: Eligible patients who had and had not undergone DXA screening were identified from among those aged 50 years or older at Kaohsiung Veterans General Hospital, Taiwan. Age, sex, screening year (index year), and Charlson comorbidity index of the DXA and non-DXA groups were matched using inverse probability of treatment weighting (IPTW) for propensity score analysis. For cost-effectiveness analysis, a societal perspective, 1-year cycle length, 20-year time horizon, and discount rate of 2% per year for both effectiveness and costs were adopted in the incremental cost-effectiveness (ICER) model. Results: The outcome analysis included 10337 patients (female:male, 63.8%:36.2%) who were screened for osteoporosis in southern Taiwan between January 1, 2012, and December 31, 2021. The DXA group had significantly better outcomes than the non-DXA group in terms of fragility fractures (7.6% vs. 12.5%, P < 0.001) and mortality (0.6% vs. 4.3%, P < 0.001). The DXA screening strategy gained an ICER of US$ -2794 per quality-adjusted life year (QALY) relative to the non-DXA at the willingness-to-pay threshold of US$ 33004 (Taiwan’s per capita gross domestic product). The ICER after stratifying by ages of 50–59, 60–69, 70–79, and ≥ 80 years were US$ -17815, US$ -26862, US$ -28981, and US$ -34816 per QALY, respectively. Conclusion: Using DXA to screen adults aged 50 years or older for osteoporosis resulted in a reduced incidence of fragility fractures, lower mortality rate, and reduced total costs. Screening for osteoporosis is a cost-saving strategy and its effectiveness increases with age. However, caution is needed when generalizing these cost-effectiveness results to all older populations because the study population consisted mainly of women.

Multidisciplinary Perspectives in Understanding Slow-moving Landslide

( Wei-an Chao ),( Ming-chien Chung ),( Keng-hao Kang ),( Chih-pin Lin ),( Tung-lin Tai ),( Hao-wen Yang ) 대한지질공학회 2019 대한지질공학회 학술발표회논문집 Vol.2019 No.2

Landslides have caused extensive infrastructure damage and threatened the human fatalities through the centuries. Among all triggered factors, massive precipitation and large earthquakes are considered to be the two key activators for pushing landslide moving, particularly for catastrophic landslides. The most acceptable mechanism resulting the landslide movement is liquefaction due to increasing water pore pressure. In this study, a landslide site has been well understood by hydrological, geophysical, geological, geodetic, geotechnical and seismological (H4GS) perspectives. Our seismic monitoring of daily relative velocity changes (dv/v) in sliding material decreased coinciding with first-half rainy period yet increased observing in post-half raining event. Geodetic survey (real-time kinematic, RTK; total station) before and after rainy period presents the vertical subsidence without any horizontal movement. The results from multidisciplinary investigation allow us to draw the conceptual model of landslide healing process caused by the water loading. Under the stability condition (F > 1.0) for each sliding materials, unconsolidated landslide colluvium and impermeable sliding surface could trap the seepage water to be as water pool, provided compact force acting on the materials below the sliding boundary. The vertical force of compaction facilitates to increasing the cohesion and strength of materials, tending the landslide material to be much stability. We demonstrated that healing process is periodically occurred but only for prolonged and intense precipitation combined with stability condition.

Quercetin-mediated Cell Cycle Arrest and Apoptosis Involving Activation of a Caspase Cascade through the Mitochondrial Pathway in Human Breast Cancer MCF-7 Cells

Chu-Chung Chou,Jai-Sing Yang,Hsu-Feng Lu,Siu-Wan Ip,Chyi Lo,Chih-Chung Wu,Jing-Pin Lin,Nou-Ying Tang,Jing-Gung Chung,Ming-Jen Chou,Ying-Hock Teng,Dar-Ren Chen 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 μM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 μM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 μM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56%to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and ΔΨ m and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.