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.

Original Article : The Risk of Cellulitis in Cirrhotic Patients: A Nationwide Population-Based Study in Taiwan

( Ming Nan Lin ),( Chen Chi Tsai ),( Tsung Hsing Hung ),( Chih Chun Tsai ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.4

Background/Aims: Cellulitis is a common infectious disease. However, the risk of cellulitis in cirrhotic patients is not well established, and whether liver cirrhosis is a risk factor for cellulitis remains unknown. This study evaluated the relationship between cellulitis and liver cirrhosis. Methods: The National Health Insurance Database, which was derived from the Taiwan National Health Insurance program, was used to identify patients. The study group consisted of 39,966 patients with liver cirrhosis, and the comparison group consisted of 39,701 randomly selected age- and sex-matched patients. Results: During the 3-year follow-up period, 2,674 (6.7%) patients with liver cirrhosis developed cellulitis, and 1,587 (4.0%) patients without liver cirrhosis developed cellulitis (p<0.001). Following a Cox`s regression analysis adjusted for age, sex, and underlying medical disorders, the cirrhotic patients demonstrated a greater risk for the occurrence of cellulitis than the non-cirrhotic patients during the 3-year period (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.55 to 1.77; p<0.001). Additionally, cirrhotic patients with complications also had a greater risk for the occurrence of cellulitis than those patients without complications (HR, 1.23; 95% CI, 1.14 to 1.33; p<0.001). Conclusions: We conclude that cirrhotic patients have a greater risk of cellulitis than non-cirrhotic patients. (Gut Liver 2012;6:482-485)

Optimizing Production of Two Potential Probiotic Lactobacilli Strains Isolated from Piglet Feces as Feed Additives for Weaned Piglets

Ming-Lun Chiang,Hsi-Chia Chen,Kun-Nan Chen,Yu-Chun Lin,Ya-Ting Lin,Ming-Ju Chen 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.8

Two probiotic strains, Lactobacillus johnsonii x-1d-2 and Lactobacillus mucosae x-4w-1, originally isolated from piglet feces, have been demonstrated to possess antimicrobial activities, antibiotic resistances and interleukin-6 induction ability in RAW 267.4 macrophages in our previous study. These characteristics make L. johnsonii x-1d-2 and L. mucosae x-4w-1 good candidates for application in feed probiotics. In this study, soybeal meal, molasses and sodium acetate were selected to optimize the growth medium for cultivation of L. johnsonii x-1d-2 and L. mucosae x-4w-1. These two strains were then freeze-dried and mixed into the basal diet to feed the weaned piglets. The effects of L. johnsonii x-1d-2 and L. mucosae x-4w-1 on the growth performance and fecal microflora of weaned piglets were investigated. The results showed that the bacterial numbers of L. johnsonii x-1d-2 and L. mucosae x-4w-1 reached a maximum of 8.90 and 9.30 log CFU/mL, respectively, when growing in optimal medium consisting of 5.5% (wt/vol) soybean meal, 1.0% (wt/vol) molasses and 1.0% (wt/vol) sodium acetate. The medium cost was 96% lower than the commercial de Man, Rogosa and Sharpe medium. In a further feeding study, the weaned piglets fed basal diet supplemented with freeze-dried probiotic cultures exhibited higher (p<0.05) body weight gain, feed intake, and gain/feed ratio than weaned piglets fed basal diet. Probiotic feeding also increased the numbers of lactobacilli and decreased the numbers of E. coli in the feces of weaned piglets. This study demonstrates that L. johnsonii x-1d-2 and L. mucosae x-4w-1 have high potential to be used as feed additives in the pig industry.

Optimizing Production of Two Potential Probiotic Lactobacilli Strains Isolated from Piglet Feces as Feed Additives for Weaned Piglets

Chiang, Ming-Lun,Chen, Hsi-Chia,Chen, Kun-Nan,Lin, Yu-Chun,Lin, Ya-Ting,Chen, Ming-Ju Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.8

Two probiotic strains, Lactobacillus johnsonii x-1d-2 and Lactobacillus mucosae x-4w-1, originally isolated from piglet feces, have been demonstrated to possess antimicrobial activities, antibiotic resistances and interleukin-6 induction ability in RAW 267.4 macrophages in our previous study. These characteristics make L. johnsonii x-1d-2 and L. mucosae x-4w-1 good candidates for application in feed probiotics. In this study, soybeal meal, molasses and sodium acetate were selected to optimize the growth medium for cultivation of L. johnsonii x-1d-2 and L. mucosae x-4w-1. These two strains were then freeze-dried and mixed into the basal diet to feed the weaned piglets. The effects of L. johnsonii x-1d-2 and L. mucosae x-4w-1 on the growth performance and fecal microflora of weaned piglets were investigated. The results showed that the bacterial numbers of L. johnsonii x-1d-2 and L. mucosae x-4w-1 reached a maximum of 8.90 and 9.30 log CFU/mL, respectively, when growing in optimal medium consisting of 5.5% (wt/vol) soybean meal, 1.0% (wt/vol) molasses and 1.0% (wt/vol) sodium acetate. The medium cost was 96% lower than the commercial de Man, Rogosa and Sharpe medium. In a further feeding study, the weaned piglets fed basal diet supplemented with freeze-dried probiotic cultures exhibited higher (p<0.05) body weight gain, feed intake, and gain/feed ratio than weaned piglets fed basal diet. Probiotic feeding also increased the numbers of lactobacilli and decreased the numbers of E. coli in the feces of weaned piglets. This study demonstrates that L. johnsonii x-1d-2 and L. mucosae x-4w-1 have high potential to be used as feed additives in the pig industry.

nonstop glumes (nsg), a novel mutant affects spikelet development in rice

Nan Wang,Yun-Feng Li,Xian-Chun Sang,Ying-Hua Ling,Fang-Ming Zhao,Zheng-Lin Yang,Guang-Hua He 한국유전학회 2013 Genes & Genomics Vol.35 No.2

The spikelet is a unique structure of grass plants,and its development involved with complicated molecular regulation network. nsg (nonstop glumes) mutant affecting spikelet development was identified from EMS-treated Jinhui10(Oryza sativa L. ssp. indica.). Mutant plants had normal glumes (inner rudimentary glume, empty glumes and lemma/palea) and pedicel at the early flowering stage, but had longer ones at later stage. An extra glume-like organ was found in 84 %of mutant individuals. The number of stamens decreased in most mutant individuals whereas three stigmas or two carpels were found in some mutant individuals. The mutant phenotype suggests that NSG is involved in the whole rice spikelet development. NSG was mapped to a 15 kb region on the chromosome 4. According to sequence analysis, a gene encoding a protein with C2H2 domain exhibited a 13 bp insertion, causing a frame shift in genomics DNA and cDNA in nsg. This gene was identified as the candidated gene of NSG. The mutation of NSG influenced the transcription level of some floral hometic genes. The expression of OsMADS4, OsMADS16, DL and OsMADS3 decreased distinctly, and OsMADS1 increased in nsg panicle, suggests that NSG affected spikelet development through influencing the expression of floral hometic genes.

Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for the Treatment of HCV Genotype 1b Infection without Baseline NS5A Resistance-Associated Variants (DARING)-Interim Report

( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.

Gene Mapping and Expression Analysis of a Novel Mutant reproduce organs absent (roa) in Rice

Nan Wang,Xian Chun Sang,Yun Feng Li,Ying Hua Ling,Fang Ming Zhao,Zheng Lin Yang,Guang Hua He 한국유전학회 2009 Genes & Genomics Vol.31 No.5

Mutant plays an important role in function analysis in plant. A rice flower mutant reproduce organs absent (roa), showing a stable inheritance during several years of study, was identified in rice (Oryza sativa L. ssp. Indica) cultivar Jinhui10 treated with EMS and used in this study. This mutant showed following: elongated palea and pedicle; absence of inner three whorls of floral organs; multi-whorls glume like organs inside the lemma/palea; spikelet meristem like organ upon the pedicle. These phenotypes suggested that ROA is a key gene in rice spikelet development. Genetic analysis confirmed that the mutant traits were controlled by a single recessive nuclear gene. By gene mapping, ROA was restricted between two SSR markers RM221 and RM1342 on the chromosome 2. It concluded that ROA was a novel gene involving in flower development in rice. Besides, the mutation of ROA influenced the transcription level of floral homeotic genes; the expression of floral homeotic genes decreased in roa panicle compared with wild-type, and it suggested that ROA affected flower development by influencing the expression of floral homeotic genes.

Risk Assessment of Breast Cancer in Guangdong, China: A Community-based Survey

Lin, Ying,Shao, Nan,Zhang, Yun-Jian,Wu, Zhuang-Hong,Li, Zhi-Bin,Ren, Ze-Fang,Wang, Shen-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Objectives: Compared with Western countries, the incidence rates for breast cancer in China are still low. However, breast cancer appears to be hitting Chinese women at a much younger age, with a peak between 40 and 50 years. Furthermore, breast tumors of Asian women have molecular and genetic characteristics that are different from those of Caucasian women. Methods: A community-based study was designed to evaluate the relationship between lifestyles and breast cancer risk in Chinese women residing in Guangzhou. 16,314 subjects completed the questionnaire. Potential confounding factors included sociodemographic characteristics. Results: 33 individuals reported a history of breast cancer, yielding a prevalence rate of 202.3/100000. Associations between subjects' demographic and breast cancer risk factors were assessed. Breast cancer is associated with family history of breast cancer, X-rays received, benign breast disease and hyperlipoidemia or hypercholesteremia with elevated odds ratios. Conclusions: Family history of breast cancer, X-ray received benign breast disease and hyperlipoidemia or hypercholesteremia were significantly associated with risk of breast cancer and may havepotential for breast cancer risk assessment.

Optimization of the Viability of Probiotics in a Fermented Milk Drink by the Response Surface Method

Chen, Ming-Ju,Chen, Kun-Nan,Lin, Chin-Wen Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.5

Growth promoters were added to skim milk to retain the viability of Lactobacillus acidophilus and Bifidobacterium longum to help the product meet the "therapeutic minimum" at the time of consumption. The experiments were divided into two parts. The first part of the study used chicory inulin, isomalto-oligosaccharides and sucrose to investigate the effects of sugars on the activity of L. acidophilus and B. longum. The results indicated that the addition of isomalto-oligosaccharides stimulated growth of L. acidophilus and B. longum, resulting in a higher level of the probiotics after one month storage and yielded better $\beta$-galactosidase activity during fermentation. The second part studied the effects of three growth promoters on the viability of the probiotic cultures and the response surface method was employed to find the optimal ratio for addition of the growth promoters. The optimal ratio for added calcium gluconate, sodium gluconate and N-acetylglucosamine in fermented milk drinks were established. The response surface method proved to be a very effective way of optimizing the activity of probiotic cultures when developing a new fermented milk drink.

Development and Verification of an Optimum Composition Model for a Synbiotic Fermented Milk Using Sequential Quadratic Programming Techniques

Chen, Ming-Ju,Chen, Kun-Nan,Lin, Chin-Wen Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.10

The purpose of this research was to develop an optimum composition model for a new synbiotic fermented dairy product with high probiotic cell counts, and to experimentally verify this model. The optimum composition model indicated the growth promoter ratio that could provide the highest growth rate for probiotics in this fermented product. Different levels of growth promoters were first blended with milk to improve the growth rates of probiotics, and the optimum composition model was determined. The probiotic viabilities and chemical properties were analyzed for the samples made using the optimal formula. The optimal combination of the growth promoters for the synbiotic fermented milk product was 1.12% peptides, 3% fructooligosaccharides (FOS), and 1.87% isomaltooligosaccharides (IMO). A product manufactured according to the formula of the optimum model was analyzed, showing that the model was effective in improving the viability of both Lactobacillus spp. and Bifidobacterium spp.