The Effect of the First Spontaneous Bacterial Peritonitis Event on the Mortality of Cirrhotic Patients with Ascites: A Nationwide Population-Based Study in Taiwan

( Tsung-hsing Hung ),( Chen-chi Tsai ),( Yu-hsi Hsieh ),( Chih-chun Tsai ),( Chih-wei Tseng ),( Kuo-chih Tseng ) 대한간학회 2016 Gut and Liver Vol.10 No.5

Background/Aims: Spontaneous bacterial peritonitis (SBP) contributes to poorer short-term mortality in cirrhotic patients with ascites. However, it is unknown how long the effect of the first SBP event persists in these patients. Methods: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify and enroll 7,892 cirrhotic patients with ascites who were hospitalized between January 1 and December 31, 2007. All patients were free from episodes of SBP from 1996 to 2006. Results: The study included 1,176 patients with SBP. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in this group were 21.8%, 38.9%, 57.5%, and 73.4%, respectively. The overall 30-day, 90-day, 1-year, and 3-year mortality rates in the non-SBP group were 15.7%, 32.5%, 53.3%, and 72.5%, respectively. After adjusting for gender, age, and other medical comorbidities, the adjusted hazard ratios of SBP for 30-day, 30- to 90-day, 90-day to 1-year, and 1- to 3-year mortality were 1.49 (95% confidence interval [CI], 1.30 to 1.71), 1.19 (95% CI, 1.02 to 1.38), 1.04 (95% CI, 0.90 to 1.20), and 0.90 (95% CI, 0.77 to 1.05), respectively, compared with the non-SBP group. Conclusions: The effect of SBP on the mortality of cirrhotic patients with ascites disappeared in those surviving more than 90 days after the first SBP event. (Gut Liver 2016;10:803-807)

Law and Insurance Claim of General Average: a Comparative Study on York-Antwerp Rules, the Law of English and Taiwan

( Tseng Wen Jui ),( Tseng Kuo Shyong ),( Yang Yi Chih ) 한국해운물류학회(구 한국해운학회) 2003 해운물류연구 Vol.39 No.-

General average system is a special part of maritime law, which is considered to have existed long before insurance policies, and the general average loss is to be made good by the contribution of all concerned, when the adventure is saved. Different insurance policies will cover the sacrifices and extraordinary expenses and general average contributions arising from a general average contributions arising from a general average act. This paper will study the underwriter liability for general average losses according to Marine Insurance Act, 1906. After inductive analysis, this article proposes revised suggestions of the law pertaining to the claim of general average for an underwriter in Taiwan.

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.

The Natural Flavonoid Apigenin Suppresses Th1- and Th2-Related Chemokine Production by Human Monocyte THP-1 Cells Through Mitogen-Activated Protein Kinase Pathways

Ching-Hua Huang,Po-Lin Kuo,Ya-Ling Hsu,Tai-Tsung Chang,Hsing-I Tseng,Yu-Te Chu,Chang-Hung Kuo,Huan-Nan Chen,Chih-Hsing Hung 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.2

Dietary flavonoids have various biological functions, and there is increasing evidence that reduced prevalence and severity of allergic reactions are associated with the intake of flavonoids. Among natural flavonoids, apigenin is a potent anti-inflammatory agent. However, the mechanisms of apigenin's effect remain uncertain. Monocyte-derived chemokine (MDC) plays a pivotal role in recruiting T-helper (Th) 2 cells in the allergic inflammation process. In the late phase of allergic inflammation, the Th1 chemokine interferon-inducible protein 10 (IP-10) has also been found in elevated levels in the bronchial alveolar fluid of asthmatic children. We used human THP-1 monocyte cells, pretreated with or without apigenin, prior to lipopolysaccharide stimulation. By means of enzyme-linked immunosorbent assay, we found that apigenin inhibited production of both MDC and IP-10 by THP-1 cells and that the suppressive effect of apigenin was not reversed by the estrogen receptor antagonist ICI182780. The p65 phosphorylation of nuclear factor κB remained unaffected, but the phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase mitogen-activated protein kinase pathways were all blocked. We found that inhibition of c-raf phosphorylation might be the target of apigenin's anti-inflammation property.

Real-World Effectiveness and Safety of SOF/LDV for Pa-tients with Chronic Hepatitis C in Taiwan

( Ching-chu Lo ),( Pin-nan Cheng ),( Chi-yi Chen ),( Chung-feng Huang ),( Hsing-tao Kuo ),( Kuo-chih Tseng ),( Yi-hsiang Huang ),( Chi-ming Tai ),( Cheng-yuan Peng ),( Ming-jong Bair ),( Chien-hung Ch 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in CHC and CHB Coinfection Patients: A Phase 3 Study in Taiwan

( Chun-Jen Liu ),( Wan-Long Chuang ),( I-Shyan Sheen ),( Horng-Yuan Wang ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ting-Tsung Chang ),( Benede tta Massetto ),( Jenny Yang ),( Gregory Camus ),( Fangqiu Zh 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Patients co-infected with HCV and HBV have more rapid progression and worse outcomes than mono-infected patients. Taiwan has among the highest prevalence of chronic HCV/HBV coinfection in Southeast Asia. This study evaluated the safety and efficacy of an all-oral treatment with ledipasvir(LDV)/sofosbuvir(SOF) for 12 weeks in chronic HCV and HBV coinfection. Methods: Patients with or without compensated cirrhosis chronic HCV GT1/GT2 and HBV (HBsAg+) treatment naïve were enrolled into open-label, receiving LDV 90 mg/SOF 400 mg(QD) for 12 weeks. The primary efficacy endpoint is SVR12. HBV DNA was monitored at all study visits and it will be monitored for 2 years post-treatment. Results: A total of 111 patients (68[61%] with GT1 and 43[39%] with GT2) were enrolled and treated. The majority were female(62%), treatment naive(67%), and non-cirrhotic(85%), with a mean age of 55 years and mean BMI of 24.5kg/m2. All but one was HBeAg negative. Mean baseline HBV DNA was 2.1 log10IU/mL. SVR4 was 100%(111/111). The mean change in HBV DNA ranged from -0.06 log10IU/mL at week 1 to +0.49 log10IU/mL at follow-up visit 4; HBV DNA kinetics are shown in Fig 1. 60(54%) patients had an increase in HBV DNA> 10 x BL or became HBV DNA > LLOQ. No patients had ALT ≥ 2 X baseline. No patients discontinued treatment due to adverse events (AEs). Three patients had serious AEs(optic neuritis, post procedural bleeding and duodenal ulcer bleeding; none was considered drug related). Conclusions: In chronic HCV/HBV infection patients, LDV/SOF for 12 weeks resulted in an SVR4 rate of 100%. Although most patients had an increase in HBV DNA during treatment, this was not associated with ALT elevations ≥2 X baseline, and no patients started HBV therapy to date. This all-oral, interferon-free regimen was well tolerated, supporting its potential as a treatment option for HCV/HBV co-infected patients.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

( Chen-hua Liu ),( Chi-yi Chen ),( Wei-wen Su ),( Chun-jen Liu ),( Ching-chu Lo ),( Ke-jhang Huang ),( Jyh-jou Chen ),( Kuo-chih Tseng ),( Chi-yang Chang ),( Cheng-yuan Peng ),( Yu-lueng Shih ),( Chia 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.4

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 ㎡/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 ㎡/month; P<0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis. (Clin Mol Hepatol 2021;27:575-588)

Tenofovir Alafenamide for Chronic Hepatitis B Patients with Advanced Fibrosis and Partial Virologic Responses to Oral Nucleos(T)Ide Analogues- Interim Report

( Ming-lung Yu ),( Ming-lun Yeh ),( Chi-yi Chen ),( Pin-nan Cheng ),( Ming-jong Bair ),( Jyh-jou Chen ),( Ching-chu Lo ),( Chi-ming Tai ),( Ching-yang Tsai ),( Kuo-chih Tseng ),( Chien-hung Chen ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Insufficient data regarding the treatment strategy for partial response to nucleot(s)ide analogue (NUC) raised the aim of investigating tenofovir alafenamide (TAF) switching for chronic hepatitis B (CHB) patients with advanced fibrosis and partial response to other NUCs. Methods: CHB patients with advanced fibrosis (stage 3 or 4) and under NUC (except TAF) therapy with detectable hepatitis B virus (HBV) DNA for >52 weeks are enrolled to TAF 25 mg/day for 96 weeks. The objectives are viral suppression, alanine aminotransferase (ALT) normalization and safety. Results: From Feb. 2019, 34 patients, including 21 (61.8%) with entecavir, 10 (29.4%) TDF and 3 (8.8%) lamivudine or adefovir, were enrolled (15 [44.1%] male, median 53 years). The fibroscan demonstrated a mean of 10.5 kPa (7 [20.6%] cirrhotic). Sixteen (47.1%) patients were HBV e antigen positive, seven (20.6%) had YMDD mutation. The median HBV DNA level declined from 68.5 IU/mL at enrollment to 27.0 IU/mL at 4^th week, and undetectable at 12^th, 24^th, 36^th week, respectively, after TAF switching, with undetectable HBV DNA in 14/34 (41.2%), 17/33 (51.5%), 15/25 (60.0%), and 9/15 (60.0%) patients and rate of ALT normalization (≤40 U/L) of 85.3%, 85.3%, 84.8%, 92.0%, and 80.0%, respectively, after TAF switching. (figure 1) Two patients experienced transient virological breakthrough and another one developed at the final time follow up. Serum creatinine and eGFR levels were stable after TAF switching (figure 1). Two patients early terminated including one at 12^th week due to personal reason, and another one accidently died at 20^th week due to acute heart attack. Others suffered only mild degrees of adverse events which were considered unrelated to treatment. Conclusions: The preliminary results demonstrated the TAF switching is effective and safe in viral suppression for CHB patients with advanced fibrosis and partial virologic responses to other NUCs.