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Yu, Ming-Lung

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Ming-Lung

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Yu, Ming-Lung
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    Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy
    (Impact Journals LLC, 2016) Lu, Ming-Ying; Huang, Ching-I; Hsieh, Ming-Yen; Hsieh, Tusty-Juan; Hsi, Edward; Tsai, Pei-Chien; Tsai, Yi-Shan; Lin, Ching-Chih; Hsieh, Meng-Hsuan; Liang, Po-Cheng; Lin, Yi-Hung; Hou, Nai-Jen; Yeh, Ming-Lun; Huang, Chung-Feng; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Jee-Fu; Chuang, Wan-Long; Dai, Chia-Yen; Yu, Ming-Lung
    Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype.
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    Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients
    (Nature Publishing Group UK, 2017) Lee, Mei-Hsuan; Huang, Chung-Feng; Lai, Hsueh-Chou; Lin, Chun-Yen; Dai, Chia-Yen; Liu, Chun-Jen; Wang, Jing-Houng; Huang, Jee-Fu; Su, Wen-Pang; Yang, Hung-Chih; Kee, Kwong-Ming; Yeh, Ming-Lun; Chuang, Po-Heng; Hsu, Shih-Jer; Huang, Ching-I; Kao, Jung-Ta; Chen, Chieh-Chang; Chen, Sheng-Hung; Jeng, Wen-Juei; Yang, Hwai-I; Yuan, Yong; Lu, Sheng-Nan; Sheen, I-Shyan; Liu, Chen-Hua; Peng, Cheng-Yuan; Kao, Jia-Horng; Yu, Ming-Lung; Chuang, Wan-Long; Chen, Chien-Jen
    This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.
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    Diversity of the association of serum levels and genetic variants of MHC class I polypeptide-related chain A with liver fibrosis in chronic hepatitis C
    (Impact Journals LLC, 2017) Huang, Chung-Feng; Huang, Ching-I; Yeh, Ming-Lun; Wang, Shu-Chi; Chen, Kuan-Yu; Ko, Yu-Min; Lin, Ching-Chih; Tsai, Yi-Shan; Tsai, Pei-Chien; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Huang, Jee-Fu; Chuang, Wan-Long; Yu, Ming-Lung
    Background/Aims Genetic variants of MHC class I polypeptide-related chain A (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is elusive. Results: Linear regression analysis revealed that sMICA were independently correlated to α-fetoprotein (β: 0.149; 95% confidence interval [CI]: 0.001, 0.003; P = 0.007)and MICA rs2596542 GG genotype (β: 0.209; 95% CI: 0.153, 0.483; P < 0.001). While patients were stratified by MICA genetic variants, advanced fibrosis was the only factor independently correlated to sMICA among A allele carriers (β: 0.234; 95% CI: 0.107, 0.543; P = 0.004) but not among non-A allele carriers. Logistic regression analysis revealed that factors associated with advanced liver fibrosis was sMICA (OR/CI: 2.996/1.428–6.287, P = 0.004) and platelet counts (OR/CI: 0.988/0.982–0.994, P < 0.001) in MICA rs2596542 A allele carriers. sMICA > 50 pg/mL provided a positive predictive value of 72 % in predicting advanced liver fibrosis (F3-4) and of 90% in significant fibrosis (> F2) in MICA rs2596542 A allele carriers. Materials and Methods Serum level and single nucleotide polymorphism at rs2596542 of MICA were tested for the association with liver fibrosis in 319 biopsy proven chronic hepatitis C patients. Conclusions: Levels of sMICA were highly correlated to liver disease severity in chronic hepatitis C patients who carried the MICA rs738409 A allele. Patients possessing the genetic predisposition had a higher likelihood of progressed liver fibrosis if they expressed higher sMICA levels.
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    Seroprevalence and clinical characteristics of viral hepatitis in transfusion-dependent thalassemia and hemophilia patients
    (Public Library of Science, 2017) Jang, Tyng-Yuan; Lin, Pei-Chin; Huang, Ching-I; Liao, Yu-Mei; Yeh, Ming-Lun; Zeng, Yu-Sheng; Liang, Po-Cheng; Hsu, Wan-Yi; Tsai, Shih-Pien; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Jee-Fu; Dai, Chia-Yen; Huang, Chung-Feng; Chiou, Shyh-Shin; Chuang, Wan-Long; Yu, Ming-Lung
    Background/Aims Transfusion dependent subjects are at a great risk of viral hepatitis infection. We aimed to evaluate the prevalence and factors associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among transfusion-dependent patients in Taiwan. Methods: A total of 140 patients (67 thalassemic patients, 70 hemophilic patients, two patients with hereditary spherocytosis and one patient with von Willebrand disease) were prospectively enrolled to evaluate the prevalence and factors associated with viral hepatitis and spontaneous HCV clearance. All patients were tested for HBV and HCV serology and virology. Two consecutive serum samples, at least 1 year apart, were collected to clarify HCV seroclearance. Results: The seropositivity rate of hepatitis B surface antigen (HBsAg), HCV antibody (anti-HCV), and both HBsAg/anti-HCV were 6.4%, 45.7% and 5%, respectively. Logistic regression analysis of factors associated with anti-HCV seropositivity included age (odds ratio/95% confidence interval [OR/CI]: 1.12/1.07–1.18, P<0.001), serum alanine aminotransferase (ALT) (OR/CI: 1.04/1.02–1.06, P<0.001) and platelet counts (OR/CI: 0.995/0.991–0.998, P = 0.002). Age was the only factor independently associated with HBsAg seropositivity (OR/CI: 1.08/1.02–1.14.4, P = 0.007). Compared to patients born before 1992, the seroprevalence of HCV among thalassemic patients decreased dramatically in those born after 1992 (46.0% vs. 11.8%, p = 0.012). The seroprevalence of HCV among hemophilic patients also decreased significantly when comparing patients born before 1987 to those born after 1987 (79.5% vs. 11.5%, p<0.001). Similarly, the seroprevalence of HBV decreased significantly in the post-vaccination cohort compared to its counterpart (13.1%, vs. 1.3%, p = 0.005). The spontaneous clearance of HCV was observed in 25.4% (15/59) of patients, and ALT was the only factor associated with it (OR/CI 0.98/0.96–1.00, P = 0.02). Conclusions: Both HBV and HCV infections are prevalent among transfusion-dependent thalassemic and hemophilic patients in Taiwan. Nevertheless, seroprevalence decreased significantly and dramatically for HCV after universal blood screening and for HBV after implementation of a universal mass vaccination program.