182 results on '"Chen, Pei–Jer"'
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2. Hepatitis B reactivation: A possible cause of coronavirus disease 2019 vaccine induced hepatitis.
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Wu, Hsin-Yun, Su, Tung-Hung, Liu, Chun-Jen, Yang, Hung-Chih, Tsai, Jia-Huei, Wei, Ming-Han, Chen, Chieh-Chang, Tung, Chien-Chih, Kao, Jia-Horng, and Chen, Pei-Jer
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COVID-19 ,CHRONIC hepatitis B ,CORONAVIRUS diseases ,HEPATITIS B ,COVID-19 vaccines ,ALANINE aminotransferase ,LIVER injuries - Abstract
Coronavirus disease 2019 (COVID-19) vaccines were rapidly implemented globally and vaccine-associated immune-related hepatitis was recently reported. We aim to investigate its impact in regions endemic of chronic hepatitis B (CHB). We retrospectively collected patients who developed hepatitis within 90 days after COVID-19 vaccination in Taiwan. The mechanisms of hepatitis included vaccine induced liver injury (VILI) and immune-related hepatitis, which are direct liver injuries defined as aspartate or alanine aminotransferase (AST or ALT) increased ≥ 5-fold upper limit of normal (ULN) and/or AST or ALT ≥ 3-fold of ULN with concurrent total bilirubin ≥ 2-fold of ULN. Indirect liver injury due to HBV reactivation was defined as HBsAg reverse seroconversion or significant rise in HBV DNA level. The demographics, clinical data, and course of hepatitis were compared statistically. Twenty-five patients were included with a median age of 54. The culprit vaccines were ChAdOx1 nCoV-19 (n = 9), mRNA-1273 (n = 12), and BNT162b2 (n = 4). The characteristics of hepatitis were comparable regardless of vaccine subtypes. The median onset of hepatitis was 25 days post vaccination, with a peak of 10-fold ALT-increase. The etiologies included HBV reactivation (n = 10), VILI (n = 10), and immune-related hepatitis (n = 5). HBV reactivation accounts for 90% of vaccine-induced hepatitis in patients of CHB (n = 10), and two patients died. Patients with initial AST levels >500 U/L increased 27-fold risks of liver injury greater than moderate severity compared with those without. COVID-19 vaccine induced hepatitis is a clinical significant complication, and HBV reactivation may account for a possible mechanism. [ABSTRACT FROM AUTHOR]
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- 2024
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3. HBV DNA Integration into Telomerase or MLL4 Genes and TERT Promoter Point Mutation as Three Independent Signatures in Subgrouping HBV-Related HCC with Distinct Features
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Li, Chiao-Ling, Hsu, Chia-Lang, Lin, You-Yu, Ho, Ming-Chih, Chen, Chi-Ling, Ho, Tung-Ching, Lin, Yung-Feng, Tsai, Shih-Feng, Tzeng, Sheng-Tai, Huang, Chin-Fang, Wang, Ya-Chun, Yeh, Shiou-Hwei, and Chen, Pei-Jer
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Introduction:A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely, the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform. Methods:A total of 153 HBV-HCCs after surgical resection were subjected to capture sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC. Results:They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate, and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort. Conclusion:A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies.
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- 2024
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4. Pre-operative gamma-glutamyl transferase levels predict outcomes in hepatitis B-related hepatocellular carcinoma after curative resection.
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Su, Tung-Hung, Huang, Shang-Chin, Chen, Chi-Ling, Hsu, Shih-Jer, Liao, Sih-Han, Hong, Chun-Ming, Tseng, Tai-Chung, Liu, Chen-Hua, Yang, Hung-Chih, Wu, Yao-Ming, Liu, Chun-Jen, Chen, Pei-Jer, and Kao, Jia-Horng
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HEPATOCELLULAR carcinoma ,CHRONIC hepatitis B ,HEPATITIS B virus ,HEPATITIS ,SURGICAL excision ,REGRESSION analysis - Abstract
Surgical resection is a curative therapy for early-stage hepatocellular carcinoma (HCC); however, HCC recurrence is not uncommon. Identifying outcome predictors helps to manage the disease. Gamma-glutamyl transferase (GGT) may predict the development of HCC, but its role to predict the outcomes after surgical resection of HCC was unclear. This study aimed to investigate pre-operative GGT levels for outcome prediction in patients with hepatitis B virus (HBV)-related HCC. We conducted a retrospective cohort study to include patients with HBV-related HCC receiving surgical resection. Clinical information, HCC characteristics and usage of antiviral therapy were collected. A time-dependent Cox proportional hazard regression analysis were used to predict HCC recurrence and survival. A total of 699 consecutive patients with HBV-related HCC who received surgical resection with curative intent between 2004 and 2013 were included. After a median of 4.4 years, 266 (38%) patients had HCC recurrence. Pre-operative GGT positively correlated with cirrhosis, tumor burden and significantly increased in patients to develop HCC recurrence. Multivariable analysis demonstrated that pre-operative GGT ≥38 U/L increased 57% risk (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.20–2.06) of recurrent HCC after adjustment for confounding factors. Specifically, pre-operative GGT ≥38 U/L predicted early (<2 years) HCC recurrence (HR: 1.94, 95% CI: 1.30–2.89). Moreover, pre-operative GGT ≥38 U/L predicted all-cause mortality (HR: 1.73, 95% CI: 1.06–2.84) after surgery. Pre-operative GGT levels ≥38 U/L independently predict high risks of HCC recurrence and all-cause mortality in HBV-related HCC patients receiving surgical resection. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Optimizing Survival Benefit by Surgical Resection by the Seven-Eleven Criteria in Barcelona Clinic Liver Cancer Stage A/B Hepatocellular Carcinoma beyond the Milan Criteria
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Huang, Chian-Tzu, Chu, Yu-Long, Su, Tung-Hung, Huang, Shang-Chin, Tseng, Tai-Chung, Hsu, Shih-Jer, Liao, Sih-Han, Hong, Chun-Ming, Liu, Chen-Hua, Yang, Hung-Chih, Liu, Chun-Jen, Chen, Pei-Jer, and Kao, Jia-Horng
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Introduction:Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria is in debate. We aimed to identify candidates for surgical resection (SR) in Barcelona Clinic Liver Cancer (BCLC)-A/B HCC beyond the Milan criteria with survival benefit. Methods:Patients with BCLC-A/B HCC beyond the Milan criteria at the National Taiwan University Hospital during 2005 and 2019 were screened, and those who received transarterial chemoembolization (TACE) or SR were consecutively included. The tumor burden was classified by the seven-eleven criteria into low (≤7), intermediate (7–11), or high (>11). Multivariable Cox proportional hazard regression analysis was used for outcome prediction. Results:Overall, 474 patients who received SR (n= 247) and TACE (n= 227) were enrolled. Patients who underwent SR were significantly younger with better liver reserve. There were 76 (31%) and 129 (57%) deaths in the SR and TACE groups after a median follow-up of 3.9 and 2.1 years, respectively. The seven-eleven criteria could distinguish median overall survival (OS) among low (n= 149), intermediate (n= 203), and high (n= 122) tumor burden groups (7.7 vs. 6.9 vs. 2.8 years, respectively, p< 0.001). Patients receiving SR had a significantly higher median OS compared with TACE in those with intermediate (8.2 vs. 2.6 years, p< 0.001) and high (5.6 vs. 1.5 years, p= 0.001) tumor burden. After adjustment for age, sex, and liver reserve, SR was predictive for better OS in intermediate (adjusted hazard ratio [aHR]: 0.45, 95% confidence interval [CI]: 0.27–0.75) and high tumor burden groups (aHR: 0.54, 95% CI: 0.32–0.92). The survival benefit of SR especially confines to patients within 3 tumors. Conclusions:In patients with BCLC-A/B HCC beyond the Milan criteria with tumor burden beyond the up-to-7 criteria but within 3 tumors, SR has better OS than TACE and should be considered in resectable patients.
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- 2023
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6. Long-term durability of sustained virologic response for hepatitis C virus infection in solid organ transplant recipients receiving direct-acting antivirals.
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Liu, Chen-Hua, Chen, Yih-Sharng, Tsai, Meng-Kun, Wang, Sheoi-Shen, Lee, Chih-Yuan, Tsao, Chuan-I, Liu, Chun-Jen, Su, Tung-Hung, Tseng, Tai-Chung, Huang, Shang-Chin, Wu, Jo-Hsuan, Chen, Pei-Jer, and Kao, Jia-Horng
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HEPATITIS C ,TRANSPLANTATION of organs, tissues, etc. ,ANTIVIRAL agents ,HEPATITIS C virus ,KIDNEY transplantation - Abstract
Data are limited regarding the long-term durability of sustained virologic response (SVR) in solid organ transplant recipients who achieve SVR 12 with direct-acting antivirals (DAAs) for hepatitis C virus (HCV). We reported the virologic outcomes in 42 recipients who received DAAs for acute or chronic HCV infection after heart, liver, and kidney transplantation. After achieving SVR 12 , all recipients received HCV RNA surveys at SVR 24 , and biannually until the last visit. If HCV viremia was detected during the follow-up period, direct sequencing and phylogenetic analysis were performed to confirm late relapse or reinfection. Sixteen (38.1%), 11 (26.2%), and 15 (35.7%) patients underwent heart, liver and, kidney transplantation. Thirty-eight (90.5%) received sofosbuvir (SOF)-based DAAs. No recipients had late relapse or reinfection after a median (range) of post-SVR 12 follow-up 4.0 (1.0–6.0) years. We demonstrate that the durability of SVR in solid organ transplant recipients is excellent once SVR 12 is achieved with DAAs. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Serum cytokine profiles predict outcomes of chronic hepatitis B patients discontinuing entecavir or tenofovir therapy.
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Lin, Meng-Ju, Su, Tung-Hung, Liu, Chun-Jen, Yang, Hung-Chih, Chen, Chi-Ling, Liou, Jyh-Ming, Tseng, Tai-Chung, Liu, Chen-Hua, Hong, Chun-Ming, Chen, Pei-Jer, and Kao, Jia-Horng
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CHRONIC hepatitis B ,HEPATITIS associated antigen ,TUMOR necrosis factors ,CYTOKINES ,TENOFOVIR - Abstract
Distinct hepatitis relapse has been observed after discontinuing entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients. End-of-therapy (EOT) serum cytokines were compared and used for outcome prediction. A total of 80 non-cirrhotic CHB patients in a tertiary medical center in Taiwan who discontinued ETV (n = 51) or TDF (n = 29) therapy after fulfilling the APASL guidelines were prospectively enrolled. Serum cytokines were measured at EOT and 3rd month afterwards. Multivariable analysis was performed to predict virological relapse (VR, HBV DNA >2000 IU/mL), clinical relapse (CR, VR and alanine aminotransferase > 2-fold upper limit of normal) and hepatitis B surface antigen (HBsAg) seroclearance. Compared with TDF group, ETV stoppers had greater interleukin 5 (IL-5), IL-12 p70, IL-13, IL-17 A and tumor necrosis factor alpha (TNF-alpha) (all P < 0.05) at EOT. Older age, TDF use, higher EOT HBsAg and IL-18 (Hazard ratio [HR], 1.01; 95% CI, 1.00–1.02) levels at EOT predicted VR, while older age, higher EOT HBsAg and IL-7 (HR, 1.25; 95% CI, 1.00–1.56) levels predicted CR. In TDF stoppers, higher IL-7 (HR, 1.29; 95% CI, 1.05–1.60) and IL-18 (HR, 1.02; 95% CI, 1.00–1.04) levels predicted VR, while IL-7 (HR, 1.34; 95% CI, 1.08–1.65) and interferon-gamma (IFN-gamma) (HR, 1.08; 95% CI, 1.02–1.14) levels predicted CR. A lower EOT HBsAg level was associated with HBsAg seroclearance. Distinct cytokine profiles were observed after stopping ETV or TDF. Higher EOT IL-7, IL-18, and IFN-gamma could be probable predictors for VR and CR in patients discontinuing NA therapies. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Entecavir Prevents HBV Reactivation During Direct Acting Antivirals for HCV/HBV Dual Infection: A Randomized Trial.
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Cheng, Pin-Nan, Liu, Chun-Jen, Chen, Chi-Yi, Tseng, Kuo-Chih, Lo, Ching-Chu, Peng, Cheng-Yuan, Lin, Chih-Lin, Chiu, Hung-Chih, Chiu, Yen-Cheng, and Chen, Pei-Jer
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A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue. Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level >10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level >2-fold the upper limit of normal in addition to HBVr). Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P <.001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment. Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients. ClinicalTrials.gov no: NCT04405011. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for treating patients with hepatitis C virus reinfection following direct‐acting antiviral‐induced sustained virologic response
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Liu, Chen‐Hua, Liu, Chun‐Jen, Su, Tung‐Hung, Tseng, Tai‐Chung, Chen, Pei‐Jer, and Kao, Jia‐Horng
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Data regarding the patient characteristics of hepatitis C virus (HCV) reinfection following viral eradication by a prior course of direct‐acting antivirals (DAAs) and the clinical performance of pangenotypic DAAs to retreat such patients are lacking. The demographics and potential routes of transmission were shown in 22 patients with confirmed reinfection following HCV clearance by a prior course of DAAs. Twenty patients received retreatment with pangenotypic sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) according to label recommendations. The sustained virologic response (SVR12) rates and the tolerance following treatment were reported. The incidence rates of reinfection among human immunodeficiency virus (HIV)‐positive and HIV‐negative patients were 8.33 per 100 person‐years (95% CI: 5.33‐12.78) and 0.30 per 100 person‐years (95% CI: 0.12‐0.77), respectively. Eighteen (81.8%) patients had HIV coinfection. The elapsed time between SVR12and reinfection ranged from 3 to 36 months. Twenty (90.9%) patients had different viral genotypes/subtypes before and after HCV reinfection. Prior to reinfection, 15 (68.2%) patients achieved SVR12using SOF/VEL or GLE/PIB. Twelve and eight patients were retreated with SOF/VEL for 12 weeks and GLE/PIB for 8 weeks, respectively, in whom SVR12was all achieved. All patients completed the assigned course of retreatment without interruption and all had excellent tolerance. The risk of HCV reinfection is higher in HIV‐positive patients than HIV‐negative patients following DAA‐induced SVR. Treating reinfected patients with SOF/VEL or GLE/PIB as DAA‐naïve patients has excellent effectiveness and tolerance, irrespective of the type of prior DAA exposure or viral genotypes/subtypes.
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- 2023
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10. Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) predicts complete responses of transarterial chemoembolization for hepatocellular carcinoma.
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Wang, Sung-Yin, Su, Tung-Hung, Chen, Bang-bin, Liu, Chun-Jen, Liu, Chen-Hua, Yang, Hung-Chih, Tseng, Tai-Chung, Chen, Pei-Jer, and Kao, Jia-Horng
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VITAMIN K ,CHEMOEMBOLIZATION ,HEPATOCELLULAR carcinoma ,PROTHROMBIN ,LIVER cancer ,ALPHA fetoproteins ,LIVER tumors ,PROTEIN precursors ,BLOOD coagulation factors ,LONGITUDINAL method - Abstract
Background/purpose: Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is a diagnostic marker for hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the standard management for intermediate stage HCC but lacks effective response predictors. We investigated the utility of PIVKA-II as a predictor of TACE response.Methods: This prospective study included consecutive patients with HCC undergoing TACE in Taiwan. Serum PIVKA-II levels were measured before and serially after TACE. Multivariable analyses were conducted to evaluate predictors of mortality, complete responses (CR) to TACE and unTACEable progression.Results: We included 46 patients with HCC (median age: 64 years, men:72%), and Barcelona Clinic Liver Cancer (BCLC) stages A (17%), B (65%), or C (17%). Before TACE, the median PIVKA-II level was 189 mAU/mL. After a median follow-up of 16 months, 27 (59%) patients died. PIVKA-II was positively correlated with tumor burden. Patients with infiltrative HCC or HCC exceeding the up-to-7 criteria had significantly higher baseline PIVKA-II levels than those without. Multivariable analysis indicated the infiltrative HCC independently predicted mortality. In patients BCLC A and B (n = 38), low baseline PIVKA-II (<26 mAU/mL) predicted CR to TACE, whereas high PIVKA-II predicted unTACEable tumor progression. Observations from a validation cohort corroborated the initial result that low PIVKA-II predicts CR. Moreover, serial PIVKA-II levels post TACE were significantly lower in patients with a CR to TACE compared with those without.Conclusion: Low baseline PIVKA-II level helps to predict a CR of TACE in patients with HCC. [ABSTRACT FROM AUTHOR]- Published
- 2022
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11. Serum cytokine/chemokine profiles predict hepatitis B reactivation in HBV/HCV co-infected subjects receiving direct-acting antiviral agents.
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Huang, Shang-Chin, Cheng, Pin-Nan, Liu, Chen-Hua, Yang, Hung-Chih, Su, Tung-Hung, Tseng, Tai-Chung, Chen, Pei-Jer, Kao, Jia-Horng, and Liu, Chun-Jen
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HEPATITIS B ,ANTIVIRAL agents ,HEPATITIS B virus ,DISEASE risk factors ,CYTOKINES - Abstract
Background/purpose: Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting.Methods: From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation).Results: There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P < 0.05). Single or combination of these cytokines helped predict clinical reactivation (all P < 0.05).Conclusion: Higher serum TNF-alpha at baseline and lower IFN-gamma at week 4 were associated with mild clinical reactivation of HBV in patients with HBV/HCV co-infection receiving DAAs. Combination of these cytokines reliably predicted HBV reactivation early. [ABSTRACT FROM AUTHOR]- Published
- 2022
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12. Serum PIVKA-II and alpha-fetoprotein at virological remission predicts hepatocellular carcinoma in chronic hepatitis B related cirrhosis.
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Su, Tung-Hung, Peng, Cheng-Yuan, Chang, Shan-Han, Tseng, Tai-Chung, Liu, Chun-Jen, Chen, Chi-Ling, Liu, Chen-Hua, Yang, Hung-Chih, Chen, Pei-Jer, and Kao, Jia-Horng
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CHRONIC hepatitis B ,ALPHA fetoproteins ,HEPATOCELLULAR carcinoma ,PROPORTIONAL hazards models ,CIRRHOSIS of the liver - Abstract
Background: The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy.Methods: Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated.Results: Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73-4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35-4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards.Conclusion: In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level. [ABSTRACT FROM AUTHOR]- Published
- 2022
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13. Exposure to Air Pollution and Survival in Follow-Up after Hepatocellular Carcinoma
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Chin, Wei-Shan, Pan, Shin-Chun, Huang, Ching-Chun, Chen, Pei-Jer, and Guo, Yue Leon
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Introduction:Air pollutants are classified as carcinogens by the International Agency for Research on Cancer. Long-term exposure to ambient particulate matter with an aerodiameter of 2.5 μm or lower (PM
2.5 ) has been reported to be linked with increased mortality due to hepatocellular carcinoma (HCC). However, the effects of air pollutants other than PM2.5 on HCC-related mortality have not been fully investigated. Accordingly, we conducted this study to assess the effect of long-term exposure to air pollutants (PM2.5 and nitrogen dioxide [NO2 ]) on HCC-related mortality. Method:In 2005, the Taiwan Liver Cancer Network (TLCN) was established by the National Research Program for Genomic Medicine to recruit liver cancer patients from 5 major medical centers in northern, central, and southern Taiwan. The TLCN had successfully recruited 9,344 patients by the end of 2018. In this study, we included 1,000 patients randomly sampled from the TLCN to assess the effect of exposure to air pollutants on HCC mortality after HCC diagnosis. Daily averages of PM2.5 and NO2 concentrations were retrieved from 77 air quality-monitoring stations and interpolated to the townships of patients’ residences by using the Kriging method. The effect of air pollutants on HCC survival was assessed using a Cox proportional hazards model. Results:A total of 940 patients were included in the analysis. After adjusting for potential confounders and mutually adjusting for co-pollutants, we observed that the hazards ratio (95% confidence interval) for HCC-related mortality for every 1-μg/m3 increase in PM2.5 concentration was 1.11 (1.08–1.14) and that for every 1-ppb increase in NO2 concentration was 1.08 (1.03–1.13). Conclusion:Our study suggests that long-term exposure to PM2.5 and NO2 was associated with decreased survival time in patients with HCC in Taiwan.- Published
- 2022
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14. Gut microbiota in the innate immunity against hepatitis B virus — implication in age-dependent HBV clearance.
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Wu, Li-Ling, Huang, Ting-Shuo, Shyu, Yu-Chiau, Wang, Chih-Lin, Wang, Hurng-Yi, and Chen, Pei-Jer
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• The tolerant liver immune environment during early life is regulated both by gut-microbiota and NF-κB subunit p65. • LPS-induced nuclear translocation of p65 in hepatic macrophages is impaired in neonate mice and only fully functioned in adult mice. • HBV may take advantage of immature hepatic immune function to establish chronic infection. • After the maturation of host immunity and gut bacteria, hepatic immune cells can induce proper response toward clearance of HBV infection. Hepatitis B virus (HBV) chronically infects 257 million people and is one of the most important liver diseases worldwide. A unique feature of HBV infection in humans is that viral clearance heavily depends on the age at exposure. Recent studies demonstrated that the virus takes advantage of immature innate immunity, especially hepatic macrophages, and not-yet-stabilized gut microbiota in early life to establish a chronic infection. The liver contains resident and infiltrating myeloid cells involved in immune responses to pathogens. They influence both innate and adaptive sectors of the immune system and their interplay with HBV has only been noticed recently. Here, we discuss how interactions between gut microbiota and hepatic macrophages influence the outcomes of HBV infection. Understanding the underlying mechanism would pave the way for the treatment of chronic HBV infection. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Metabolic Dysfunction-Associated Steatotic Liver Disease Facilitates Hepatitis B Surface Antigen Seroclearance and Seroconversion.
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Huang, Shang-Chin, Su, Tung-Hung, Tseng, Tai-Chung, Chen, Chi-Ling, Hsu, Shih-Jer, Liu, Chen-Hua, Liao, Sih-Han, Hong, Chun-Ming, Lan, Ting-Yuan, Yang, Hung-Chih, Liu, Chun-Jen, Chen, Pei-Jer, and Kao, Jia-Horng
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Hepatitis B surface antigen (HBsAg) seroclearance is the goal of functional cure for hepatitis B virus (HBV) infection. However, the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on this favorable outcome remains unclear. Patients with chronic hepatitis B (CHB) were consecutively recruited. MASLD was defined by the newly proposed disease criteria. Cumulative incidences and associated factors of HBsAg seroclearance/seroconversion were compared between the MASLD and non-MASLD groups. From 2006 to 2021, 4084 treatment-naive hepatitis B e antigen (HBeAg)-negative CHB patients were included. At baseline, CHB patients with concurrent MASLD (n = 887) had significantly lower levels of HBsAg and HBV DNA than the non-MASLD group (n = 3197). During a median follow-up of 5.0 years, MASLD was associated with a higher likelihood of HBsAg seroclearance (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.10–1.85; P =.007), and the accumulation of individual metabolic dysfunctions additively facilitated HBsAg seroclearance. In addition, a higher rate of HBsAg seroconversion was observed in patients with MASLD versus those without MASLD (aHR, 1.37; 95% CI, 1.00–1.86; P =.049). In sensitivity analysis, patients with intermittent MASLD had an intermediate probability of HBsAg seroclearance. After balancing clinical and virologic profiles by inverse probability of treatment weighting (IPTW), MASLD was still associated with a higher HBsAg seroclearance rate (IPTW-adjusted HR, 1.41; 95% CI, 1.09–1.84; P =.010). In untreated HBeAg-negative CHB patients, concurrent MASLD is associated with higher rates of HBsAg seroclearance and seroconversion. Metabolic dysfunctions have additive effects on the functional cure of CHB. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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16. Both hepatitis A and hepatitis D infections may be associated with more advanced liver disease in patients with chronic hepatitis B
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Wu, Jer‐Wei, Tseng, Tai‐Chung, Liu, Chun‐Jen, Su, Tung‐Hung, Liu, Chen‐Hua, Chen, Pei‐Jer, Chen, Ding‐Shinn, and Kao, Jia‐Horng
- Abstract
Acute infection of hepatitis A virus (HAV) causes transient but varying degrees of liver damage. In contrast, hepatitis D virus (HDV) only infects patients with chronic hepatitis B virus (HBV) infection, which may cause chronic and persistent liver damage. We aimed to explore whether infection of both hepatotropic viruses was associated with worse outcomes in patients with chronic HBV infection in a case‐control study. We collected serum and clinical data from 456 patients with chronic HBV infection, including 160, 150, and 146 patients with hepatocellular carcinoma (HCC), cirrhosis and inactive carrier status, respectively. Serum HAV‐IgG and anti‐HDV were determined retrospectively and seroprevalence rates of both markers were compared among the groups with different clinical stages. In the inactive carrier group, 101 (69.18%) and 3 (2.05%) patients had exposure to HAV and HDV infection, respectively. We found higher seropositive rates of HAV‐IgG in cirrhosis (82.67%) and HCC (99.38%) groups, but not seropositive rates of anti‐HDV (4.67% and 3.75% for cirrhosis and HCC respectively). When combining cirrhosis and HCC groups as patients with advanced liver disease, both seropositive HAV‐IgG and anti‐HDV were associated with increased risks of advanced liver disease with odds ratio of 10.65 (95% CI [confidence interval]: 2.74‐41.41, P< .001) and 12.64 (95% CI: 2.14‐74.78, P= .005), respectively. In the case‐control study of patients with chronic HBV infection, both exposure to HAV or HDV infection might be associated with increased risks of cirrhosis and HCC development.
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- 2021
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17. Autophagy restricts mitochondrial DNA damage-induced release of ENDOG (endonuclease G) to regulate genome stability
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Chao, Tung, Shih, Hsueh-Tzu, Hsu, Shih-Chin, Chen, Pei-Jer, Fan, Yu-Shan, Jeng, Yung-Ming, Shen, Zhao-Qing, Tsai, Ting-Fen, and Chang, Zee-Fen
- Abstract
ABSTRACTGenotoxic insult causes nuclear and mitochondrial DNA damages with macroautophagy/autophagy induction. The role of mitochondrial DNA (mtDNA) damage in the requirement of autophagy for nuclear DNA (nDNA) stability is unclear. Using site-specific DNA damage approaches, we show that specific nDNA damage alone does not require autophagy for repair unless in the presence of mtDNA damage. We provide evidence that after IR exposure-induced mtDNA and nDNA damages, autophagy suppression causes non-apoptotic mitochondrial permeability, by which mitochondrial ENDOG (endonuclease G) is released and translocated to nuclei to sustain nDNA damage in a TET (tet methylcytosine dioxygenase)-dependent manner. Furthermore, blocking lysosome function is sufficient to increase the amount of mtDNA leakage to the cytosol, accompanied by ENDOG-free mitochondrial puncta formation with concurrent ENDOG nuclear accumulation. We proposed that autophagy eliminates the mitochondria specified by mtDNA damage-driven mitochondrial permeability to prevent ENDOG-mediated genome instability. Finally, we showed that HBx, a hepatitis B viral protein capable of suppressing autophagy, also causes mitochondrial permeability-dependent ENDOG mis-localization in nuclei and is linked to hepatitis B virus (HBV)-mediated hepatocellular carcinoma development.Abbreviations:3-MA: 3-methyladenine; 5-hmC: 5-hydroxymethylcytosine; ACTB: actin beta; ATG5: autophagy related 5; ATM: ATM serine/threonine kinase; DFFB/CAD: DNA fragmentation factor subunit beta; cmtDNA: cytosolic mitochondrial DNA; ConA: concanamycin A; CQ: chloroquine; CsA: cyclosporin A; Dox: doxycycline; DSB: double-strand break; ENDOG: endonuclease G; GFP: green fluorescent protein; Gy: gray; H2AX: H2A.X variant histone; HBV: hepatitis B virus; HBx: hepatitis B virus X protein; HCC: hepatocellular carcinoma; I-PpoI: intron-encoded endonuclease; IR: ionizing radiation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOMP: mitochondrial outer membrane permeability; mPTP: mitochondrial permeability transition pore; mtDNA: mitochondrial DNA; nDNA: nuclear DNA; 4-OHT: 4-hydroxytamoxifen; rDNA: ribosomal DNA; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TET: tet methylcytosine dioxygenase; TFAM: transcription factor A, mitochondrial; TOMM20: translocase of outer mitochondrial membrane 20; VDAC: voltage dependent anion channel.
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- 2021
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18. Sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for chronic hepatitis C patients with direct acting antiviral failures: Implications for viral elimination in Taiwan.
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Liu, Chen-Hua, Su, Tung-Hung, Liu, Chun-Jen, Chen, Pei-Jer, Chen, Ding-Shinn, and Kao, Jia-Horng
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CHRONIC hepatitis C ,SOFOSBUVIR ,RIBAVIRIN ,HEPATITIS C virus ,HEPATITIS C - Abstract
Despite the excellent antiviral effects of direct acting antivirals (DAAs) for hepatitis C virus (HCV) infection with subsequent decrease of morbidity and mortality, a small proportion (5%) of the treated patients do not respond to first-line DAAs and have persistent viremia. Rescue therapy for patients with DAA failures is thus mandatory from both clinical and public health perspectives. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), a fixed-dose pangenotypic rescue agent, has been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for retreating HCV patients who fail prior DAA therapies. However, this agent has not been licensed by health authorities of Taiwan. Herein we reported two cases who successfully cleared HCV by using SOF/VEL/VOX plus ribavirin (RBV) after virologic failures to first-line pangenotypic SOF/VEL. Furthermore, we discussed the current unmet medical needs and clinical implications of SOF/VEL/VOX on the perspectives of HCV elimination in Taiwan. [ABSTRACT FROM AUTHOR]
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- 2020
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19. Pathologic findings of patients with nonalcoholic fatty liver disease and the impact of concurrent hepatitis B virus infection in Taiwan.
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Su, Hau-Jyun, Kao, Jia-Horng, Tseng, Tai-Chung, Yang, Hung-Chih, Su, Tung-Hung, Chen, Pei-Jer, and Liu, Chun-Jen
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FATTY liver ,HEPATITIS B virus ,VIRUS diseases ,CHRONIC hepatitis B ,HEPATITIS B ,ARTHRITIS Impact Measurement Scales ,CIRRHOSIS of the liver ,HEPATITIS viruses ,RETROSPECTIVE studies ,IMPACT of Event Scale ,DISEASE complications - Abstract
Background& Aims: Pathologic data of non-alcoholic fatty liver disease (NAFLD) was limited and the association between NAFLD and chronic hepatitis B remained unclear in Taiwan. This study aimed to determine the pathological manifestations of NAFLD and the impact of concurrent hepatitis B virus (HBV) infection in a medical center.Methods: Retrospective review of 104 consecutive random liver biopsies with the histologic diagnosis of NAFLD or cryptogenic cirrhosis from 2009 to 2018 was conducted. Clinical, biochemical and histological data were compared among various stages of NAFLD and between those with or without concurrent HBV infection.Results: Advanced fibrosis was documented in 39.42% of Taiwanese patients with NAFLD according to METAVIR scoring system and was associated with aging (odds ratio, 1.06; 95% CI, 1.03-1.10), hypertension (odds ratio, 2.97; 95% CI, 1.31-6.74), diabetes mellitus (odds ratio, 4.36; 95% CI, 1.78-10.70) and concurrent HBV infection (odds ratio, 3.55; 95% CI, 1.46-8.58) by multivariate analyses. Concurrent HBV was found in 28.57% of the NAFLD patients. Patients with concurrent HBV had lower platelet counts, longer prothrombin time/INR and higher fibrosis stage than those without CHB.Conclusion: Advanced fibrosis in patients with NAFLD was common in the biopsy series, and was related to aging, hypertension, diabetes mellitus and concurrent HBV infection. [ABSTRACT FROM AUTHOR]- Published
- 2020
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20. Data Independent Acquisition Mass Spectrometry Enhanced Personalized Glycosylation Profiling of Haptoglobin in Hepatocellular Carcinoma
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Pradita, Tiara, Chen, Yi-Ju, Su, Tung-Hung, Chang, Kun-Hao, Chen, Pei-Jer, and Chen, Yu-Ju
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Aberrant glycosylation has gained significant interest for biomarker discovery. However, low detectability, complex glycan structures, and heterogeneity present challenges in glycoprotein assay development. Using haptoglobin (Hp) as a model, we developed an integrated platform combining functionalized magnetic nanoparticles and zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) for highly specific glycopeptide enrichment, followed by a data-independent acquisition (DIA) strategy to establish a deep cancer-specific Hp-glycosylation profile in hepatitis B virus (HBV, n= 5) and hepatocellular carcinoma (HCC, n= 5) patients. The DIA strategy established one of the deepest Hp-glycosylation landscapes (1029 glycopeptides, 130 glycans) across serum samples, including 54 glycopeptides exclusively detected in HCC patients. Additionally, single-shot DIA searches against a DIA-based spectral library outperformed the DDA approach by 2–3-fold glycopeptide coverage across patients. Among the four N-glycan sites on Hp (N-184, N-207, N-211, N-241), the total glycan type distribution revealed significantly enhanced detection of combined fucosylated-sialylated glycans, which were the most dominant glycoforms identified in HCC patients. Quantitation analysis revealed 48 glycopeptides significantly enriched in HCC (p< 0.05), including a hybrid monosialylated triantennary glycopeptide on the N-184 site with nearly none-to-all elevation to differentiate HCC from the HBV group (HCC/HBV ratio: 2462 ± 766, p< 0.05). In summary, DIA-MS presents an unbiased and comprehensive alternative for targeted glycoproteomics to guide discovery and validation of glyco-biomarkers.
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- 2024
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21. Higher Hepatitis B core-specific T cell response is associated with a lower risk of clinical relapse after discontinuation of oral antiviral treatment
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Tseng, Tai-Chung, Cheng, Huei-Ru, Su, Tung-Hung, Lin, Ping-Hung, Wang, Chih-Chiang, Yang, Hung-Chih, Tsai, Cheng-Shiue, Liu, Chun-Jen, Chen, Pei-Jer, and Kao, Jia-Horng
- Abstract
Hepatitis B virus (HBV)-specific T cell response is a major host immune response to control the virus. However, it is still unclear how it affects long-term outcomes of chronic hepatitis B patients, especially those who stop nucleos(t)ide analogue (NA) therapy. We aimed to explore whether the HBV-specific T cell response at the end of treatment (EOT) was associated with clinical outcomes.
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- 2024
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22. Disease burden from foodborne illnesses in Taiwan, 2012-2015.
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Lai, Ying-Ho, Chung, Yu-An, Wu, Yun-Chun, Fang, Chi-Tai, and Chen, Pei-Jer
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FOODBORNE diseases ,VIBRIO parahaemolyticus ,FOOD pathogens ,MEDICAL care ,SALMONELLA food poisoning ,MEDICAL care costs ,GASTROENTERITIS ,DISEASE incidence ,FOOD poisoning ,ECONOMIC aspects of diseases - Abstract
Background/purpose: Foodborne disease is a global health problem. We aim to provide the first national estimate on disease burden from foodborne illnesses in Taiwan.Methods: We adopted the World Health Organization (WHO) Foodborne Disease Burden Epidemiology Reference Group (FERG) methodology framework, and used a hazard-based incidence approach to calculate disability-adjusted life year (DALY) lost to foodborne diseases. Estimated annual incidences and associated medical costs are based on the National Health Insurance research database. We redistributed incidence of unspecified acute gastroenteritis to specific foodborne pathogens, using reported bacteria, virus, parasite survey results in such cases as the reference. The percentage of foodborne illnesses not seeking medical attention is based on data reported from a nationwide survey.Results: During 2012-2015, 3,895,914 (90% confidence interval [CI]: 3,493,530-4,442,690) foodborne illnesses (1,445,384 sought medical care, with 50 deaths) occurred annually, which caused a total loss of 4974 (90%CI: 4671-5367) DALYs in Taiwan. The annual medical cost was NT$1.3 billion. Young (<5 years) children had the highest incidence. Among the 53% of foodborne illnesses cases with identifiable causal microorganisms, non-typhoid Salmonella, norovirus, and Vibrio parahaemolyticus were leading pathogens (annual foodborne incidence: 185,977, 157,656, and 99,351, respectively). Cases caused by non-typhoid Salmonella peaked in summer, while that caused by norovirus peaked in winter.Conclusion: Foodborne illnesses cause a substantial disease burden in Taiwan. Establishment of active surveillance and investigation mechanisms for the leading foodborne pathogens is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2020
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23. The role of phylogenetic analysis in clarifying the infection source of a COVID-19 patient.
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Wang, Jann-Tay, Lin, You-Yu, Chang, Sui-Yuan, Yeh, Shiou-Hwei, Hu, Bor-Hsian, Chen, Pei-Jer, and Chang, Shan-Chwen
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- 2020
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24. 2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations.
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Yu, Ming-Lung, Chen, Pei-Jer, Dai, Chia-Yen, Hu, Tsung-Hui, Huang, Chung-Feng, Huang, Yi-Hsiang, Hung, Chao-Hung, Lin, Chun-Yen, Liu, Chen-Hua, Liu, Chun-Jen, Peng, Cheng-Yuan, Lin, Han-Chieh, Kao, Jia-Horng, and Chuang, Wan-Long
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HEPATITIS C ,HIV ,HEPATITIS C virus ,HEPATITIS B virus ,CHRONIC kidney failure ,LIVER tumors ,CHRONIC hepatitis C ,ANTIVIRAL agents ,HEPATITIS viruses ,MIXED infections ,HEPATOCELLULAR carcinoma ,DISEASE complications - Abstract
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug-drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement. [ABSTRACT FROM AUTHOR]
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- 2020
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25. 2020 Taiwan consensus statement on the management of hepatitis C: part (I) general population.
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Yu, Ming-Lung, Chen, Pei-Jer, Dai, Chia-Yen, Hu, Tsung-Hui, Huang, Chung-Feng, Huang, Yi-Hsiang, Hung, Chao-Hung, Lin, Chun-Yen, Liu, Chen-Hua, Liu, Chun-Jen, Peng, Cheng-Yuan, Lin, Han-Chieh, Kao, Jia-Horng, and Chuang, Wan-Long
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HEPATITIS C ,HEPATITIS C virus ,LIVER diseases ,CHRONIC hepatitis C ,ANTIVIRAL agents ,HEPATITIS viruses - Abstract
Hepatitis C virus (HCV) infection remains a major public health issue with high prevalence in Taiwan. Recently, the advent of direct-acting antiviral (DAA) agents, with higher efficacy, excellent safety profile, and truncated treatment duration, has revolutionized the paradigm of hepatitis C treatment and made HCV elimination possible. To provide timely guidance for optimal hepatitis C management, the Taiwan Association for the Study of the Liver (TASL) established an expert panel to publish a 2-part consensus statement on the management of hepatitis C in the DAA era. After comprehensive literature review and a consensus meeting, patient-oriented, genotype-guided recommendations on hepatitis C treatment for the general and special populations have been provided based on the latest indications and scientific evidence. In the first part of this consensus, we present the epidemiology and treatment situation of hepatitis C in Taiwan, the development of DAA, pre-treatment evaluation, post sustained virologic response (SVR) monitoring, and most importantly the treatment recommendations for the general population with compensated liver disease. The second part will focus on the treatment recommendations for the special populations. [ABSTRACT FROM AUTHOR]
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- 2020
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26. Cost-effectiveness of preventing hepatitis B virus reactivation in patients with lymphoma and resolved HBV infection.
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Tsou, Hsiao-Hui, Yang, Hung-Chih, Hsiao, Chin-Fu, Hsiung, Chao A., Liu, Tsang-Wu, Chuang, Mei-Hsing, Wu, Hsiao-Yu, Hsu, Ya-Ting, Tsui, Chiung-Wen, Chen, Pei-Jer, Cheng, Ann-Lii, and Hsu, Chiun
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HEPATITIS B virus ,COST effectiveness ,DATABASE administration ,DECISION trees ,INFECTION - Abstract
Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications. Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy. The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p = 0.013). Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection. [ABSTRACT FROM AUTHOR]
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- 2020
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27. Cost-effectiveness of preventing hepatitis B virus reactivation in patients with lymphoma and resolved HBV infection.
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Tsou, Hsiao-Hui, Yang, Hung-Chih, Hsiao, Chin-Fu, Hsiung, Chao A., Liu, Tsang-Wu, Chuang, Mei-Hsing, Wu, Hsiao-Yu, Hsu, Ya-Ting, Tsui, Chiung-Wen, Chen, Pei-Jer, Cheng, Ann-Lii, Hsu, Chiun, and Taiwan Cooperative Oncology Group
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HEPATITIS B virus ,COST effectiveness ,DATABASE administration ,DECISION trees ,INFECTION ,THERAPEUTIC use of antineoplastic agents ,VIRAL antigens ,DNA ,ARTHRITIS Impact Measurement Scales ,ANTIVIRAL agents ,IMPACT of Event Scale ,LYMPHOMAS ,VIRAL antibodies ,CHRONIC hepatitis B ,DISEASE complications - Abstract
Background/purpose: Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications.Methods: Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy.Results: The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p = 0.013).Conclusion: Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection. [ABSTRACT FROM AUTHOR]- Published
- 2020
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28. Global multi-stakeholder endorsement of the MAFLD definition
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Méndez-Sánchez, Nahum, Bugianesi, Elisabetta, Gish, Robert G, Lammert, Frank, Tilg, Herbert, Nguyen, Mindie H, Sarin, Shiv K, Fabrellas, Núria, Zelber-Sagi, Shira, Fan, Jian-Gao, Shiha, Gamal, Targher, Giovanni, Zheng, Ming-Hua, Chan, Wah-Kheong, Vinker, Shlomo, Kawaguchi, Takumi, Castera, Laurent, Yilmaz, Yusuf, Korenjak, Marko, Spearman, C Wendy, Ungan, Mehmet, Palmer, Melissa, El-Shabrawi, Mortada, Gruss, Hans-Juergen, Dufour, Jean-François, Dhawan, Anil, Wedemeyer, Heiner, George, Jacob, Valenti, Luca, Fouad, Yasser, Romero‐Gomez, Manuel, Eslam, Mohammed, Abate, Maria Lorena, Abbas, Bahaa, Abbassy, Ahmed Amr, Abd El Ghany, Waleed, Abd Elkhalek, Amira, Abd ElMajeed, Emad, Abdalgaber, Mohammad, AbdAllah, Mohamed, Abdallah, Marwa, Abdallah, Nourhan, Abdelaleem, Shereen, Abdelghani, Yasser, Abdelghany, Wael, Abdelhalim, Safaa Mohamed, Abdelhamid, Wafaa, Abdelhamid, Nehal, Abdelkader, Nadia A., Abdelkreem, Elsayed, Abdelmohsen, Aly Mohamed, Abdelrahman, Awny Ali, Abd-elsalam, Sherief M, Abdeltawab, Doaa, Abduh, Abdulbaset, Abdulhakam, Nada, Abdulla, Maheeba, Abedpoor, Navid, Abenavoli, Ludovico, Åberg, Fredrik, Ablack, Omala, Abo elftouh, Mostafa, Abo-Amer, Yousry Esam-Eldin, Aboubkr, Ashraf, Aboud, Alaa, Abouelnaga, Amr M., Aboufarrag, Galal A., Aboutaleb, Ashraf, Abundis, Leticia, Adalı, Gupse, Adames, Enrique, Adams, Leon, Adda, Danjuma, Adel, Noor, Adel, Nada, Adel Sayed, Muhammad, Afaa, Taiba Jibril, Afredj, Nawal, Aghayeva, Gulnara, Aghemo, Alessio, Aguilar-Salinas, Carlos A., Ahlenstiel, Golo, Ahmady, Walid, Ahmed, Wafaa, Ahmed, Amira, Ahmed, Samah Nasser, Ahmed, Heba Mostafa, Ahmed, Rasha, Aigner, Elmar, Akarsu, Mesut, Akroush, Maisam, Akyuz, Umit, Al Mahtab, Mamun, Al Qadiri, Tahani, Al Rawahi, Yusriya, AL rubaee, Razzaq, Al Saffar, Muna, Alam, Shahinul, Al-Ani, Zaid, Albillos, Agustín, Alboraie, Mohamed, Al-Busafi, Said, Al-Emam, Mohamed, Alharthi, Jawaher, Ali, Kareem, Ali, Basma Abdelmoez, Ali, Mohammad, Ali, Raja Affendi Raja, Alisi, Anna, AL-Khafaji, Ali Raad, Alkhatry, Maryam, Aller, Rocio, Almansoury, Yahya, Al-Naamani, Khalid, Alnakeeb, Alaa, Alonso, Anna, Alqahtani, Saleh A., Alrabadi, Leina, Alswat, Khalid, Altaher, Mahir, Altamimi, Turki, Altamirano, Jose, Alvares-da-Silva, Mario R., Aly, Elsragy Adel M., Alzahaby, Amgad, Alzamzamy, Ahmed, Amano, Keisuke, Amer, Maysa A., Amin, Mona A., Amin, Sayed A., Amir, Ashraf A., Ampuero, Javier, Anas, Noha, Andreone, Pietro, Andriamandimby, Soa Fy, Anees, Mahmoud, Angela, Peltec, Antonios, Manal, Arafat, Wael, Araya, Jose Moreno, Armendariz-Borunda, Juan, Armstrong, Matthew J., Ashktorab, Hassan, Aspichueta, Patricia, Assal, Fathia, Atef, Mira, Attia, Dina, Atwa, Hoda, Awad, Reham, Awad, Mohyeldeen Abd Elaziz, Awny, Sally, Awolowo, Obafemi, Awuku, Yaw Asante, Ayada, Ibrahim, Aye, Than Than, Ayman, Sherif, Ayman, Hedy, Ayoub, Hesham, Azmy, Hosny M., Babaran, Romiro P., Badreldin, Omneya, Badry, Ahmed, Bahçecioğlu, İbrahim Halil, Bahour, Amira, Bai, Jiajia, Balaban, Yasemin, Balasubramanyam, Muthuswamy, Bamakhrama, Khaled, Banales, Jesus M, Bangaru, Babu, Bao, Jianfeng, Barahona, Jorge Suazo, Barakat, Salma, Barbalho, Sandra Maria, Barbra, Bikwa, Barranco, Beatriz, Barrera, Francisco, Baumann, Ulrich, Bazeed, Shamardan, Bech, Eva, Benayad, Aourarh, Benesic, Andreas, Bernstein, David, Bessone, Fernando, Birney, Susie, Bisseye, Cyrille, Blake, Martin, Bobat, Bilal, Bonfrate, Leonilde, Bordin, Dmitry S, Bosques-Padilla, Francisco, Boursier, Jerome, Boushab, Boushab Mohamed, Bowen, David, Bravo, Patricia Medina, Brennan, Paul N, Bright, Bisi, Broekaert, Ilse, Buque, Xabier, Burgos-Santamaría, Diego, Burman, Julio, Busetto, Luca, Byrne, Chris D., Cabral-Prodigalidad, Patricia Anne I., Cabrera-Alvarez, Guillermo, Cai, Wei, Cainelli, Francesca, Caliskan, Ali Riza, Canbay, Ali, Cano-Contreras, Ana, Cao, Hai-Xia, Cao, Zhujun, Carrion, Andres, Carubbi, Francesca, Casanovas, Teresa, Castellanos Fernández, Marlen Ivón, Chai, Jin, Chan, Siew Pheng, Charatcharoenwitthaya, Phunchai, Chavez-Tapia, Norberto, Chayama, Kazuaki, Chen, Jinjun, Chen, Lin, Chen, Zhong-Wei, Chen, Huiting, Chen, Sui-Dan, Chen, Qiang, Chen, Yaxi, Chen, Gang, Chen, En-Quang, Chen, Fei, Chen, Fei, Chen, Pei-Jer, Cheng, Robert, Cheng, Wendy, Chieh, Jack Tan Wei, Chokr, Imad, Cholongitas, Evangelos, Choudhury, Ashok, Chowdhury, Abhijit, Chukwudike, Evaristus Sunday, Ciardullo, Stefano, Clayton, Michelle, Clement, Karine, Cloa, Marie Michelle, Coccia, Cecilia, Collazos, Cristina, Colombo, Massimo, Cosar, Arif Mansur, Cotrim, Helma Pinchemel, Couillerot, Joris, Coulibaly, Alioune, Crespo, Gonzalo, Crespo, Javier, Cruells, Maria, Cua, Ian Homer Y., Dabbous, Hesham K., Dalekos, George N, D'Alia, Patricia, Dan, Li, Dao, Viet Hang, Darwish, Mostafa, Datz, Christian, Davalos-Moscol, Milagros B, Dawoud, Heba, de Careaga, Blanca Olaechea, de Knegt, Robert, de Ledinghen, Victor, de Silva, Janaka, Debzi, Nabil, Decraecker, Marie, Del Pozo, Elvira, Delgado, Teresa C, Delgado-Blanco, Manuel, Dembiński, Łukasz, Depina, Adilson, Derbala, Moutaz, Desalegn, Hailemichael, Desbois-Mouthon, Christèle, Desoky, Mahmoud, Dev, Anouk, Di Ciaula, Agostino, Diago, Moisés, Diallo, Ibrahima, Díaz, Luis Antonio, Dirchwolf, Melisa, Dongiovanni, Paola, Dorofeyev, Andrriy, Dou, Xiaoguang, Douglas, Mark W., Doulberis, Michael, Dovia, Cecil K., Doyle, Adam, Dragojević, Ivana, Drenth, Joost PH, Duan, Xuefei, Dulskas, Audrius, Dumitrascu, Dan L, Duncan, Oliver, Dusabejambo, Vincent, Dwawhi, Rev. Shem N.A., Eiketsu, Sho, El Amrousy, Doaa, El Deeb, Ahmed, El Deriny, Ghada, El Din, Hesham Salah, El Kamshishy, Salwa, El Kassas, Mohamed, El Raziky, Maissa, Elagamy, Osama A, Elakel, Wafaa, Elalfy, Dina, Elaraby, Hanaa, ElAwady, Heba, Elbadawy, Reda, Eldash, Hanaa Hassan, Eldefrawy, Manal S., Elecharri, Carol Lezama, Elfaramawy, Amel, Elfatih, Mohammed, Elfiky, Mahmoud, Elgamsy, Mohamed, Elgendy, Mohamed, El-Guindi, Mohamed A., Elhussieny, Nagi, Eliwa, Ahmed Maher, Elkabbany, Zeineb, El-Khayat, Hesham, El-Koofy, Nehal M., Elmetwalli, Alaa, Elrabat, Amr, El-Raey, Fathiya, Elrashdy, Fatma, Elsahhar, Medhat, Elsaid, Esraa M., Elsayed, Shimaa, Elsayed, Hany, Elsayed, Aly, Elsayed, Amr M., Elsayed, Hamdy, El-Serafy, Magdy, Elsharkawy, Ahmed M., Elsheemy, Reem Yehia, Elshemy, Eman Elsayed, Elsherbini, Sara, Eltoukhy, Naglaa, Elwakil, Reda, Emad, Ola, Emad, Shaimaa, Embabi, Mohamed, Ergenç, Ilkay, Ermolova, Tatiana, Esmat, Gamal, Esmat, Doaa M., Estupiñan, Enrique Carrera, Ettair, Said, 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Martín, Palle, Sirish, Pan, Ziyan, Pan, Xiao-Yan, Pan, Qiuwei, Papaefthymiou, Apostolis, Paquissi, Feliciano Chanana, Par, Gabriella, Parkash, Arit, Payawal, Diana, Peltekian, Kevork M., Peng, Xuebin, Peng, Liang, Peng, Ying, Pengoria, Rahul, Perez, Martina, Pérez, José Luis, Pérez, Norma Marlene, Persico, Marcello, Pessoa, Mário Guimarães, Petta, Salvatore, Philip, Mathew, Plaz Torres, Maria Corina, Polavarapu, Naveen, Poniachik, Jaime, Portincasa, Piero, Pu, Chunwen, Pürnak, Tuğrul, Purwanto, Edhie, Qi, Xiaolong, Qi, Xingshun, Qian, Zibing, Qiang, Zhao, Qiao, Zengpei, Qiao, Liang, Queiroz, Alberto, Rabiee, Atoosa, Radwan, Manal, Rahetilahy, Alain Marcel, Ramadan, Yasmin, Ramadan, Dina, Ramli, Anis Safura, Ramm, Grant A., Ran, Ao, Rankovic, Ivan, RAO, Huiying, Raouf, Sara, Ray, Sayantan, Reau, Nancy, Refaat, Ahmed, Reiberger, Thomas, Remes-Troche, Jose M, Reyes, Eira Cerda, Richardson, Ben, Ridruejo, Ezequiel, Riestra Jimenez, Sergio, Rizk, Ibrahim, Roberts, Stuart, Roblero, Juan Pablo, Robles, Jorge Alberto Prado, Rockey, Don, Rodríguez, Manuel, Rodríguez Hernández, Heriberto, Román, Eva, Romeiro, Fernando Gomes, Romeo, Stefano, Rosales-Zabal, Jose Miguel, Roshdi, Georgina R., Rosso, Natalia, Ruf, Andres, Ruiz, Patricia Cordero, Runes, Nelia R., Ruzzenente, Andrea, Ryan, Marno, Saad, Ahmed, Sabbagh, Eman BE, Sabbah, Meriam, Saber, Shimaa, Sabrey, Reham, Sabry, Ramy, Saeed, Maysaa Abdallah, Said, Dina, Said, Ebada M, Sakr, Mohammad Amin, Salah, Yara, Salama, Rabab Maamoun, Salama, Asmaa, Saleh, Hussein, Saleh, Ahmed, Salem, Ahmed, Salem, Ahmed Thabet, Salifou, Alkassoum, Salih, Aso Faeq, Salman, Abdallah, Samouda, Hanen, Sanai, Faisal, Sánchez-Ávila, Juan Francisco, Sanker, Lakshumanan, Sano, Tomoya, Sanz, Miquel, Saparbu, Tobokalova, Sawhney, Rohit, Sayed, Fatma, Sayed, Sayed A., Sayed, Ashraf Othman, Sayed, Manar, Sebastiani, Giada, Secadas, Laura, Sediqi, Khawaja Qamaruddin, Seif, Sameh, Semida, Nady, Şenateş, Ebubekir, Serban, Elena Daniela, Serfaty, Lawrence, Seto, Wai-Kay, Sghaier, Ikram, Sha, Min, Shabaan, Hamada M., Shalaby, Lobna, Shaltout, Inass, Sharara, Ala I., Sharma, Vishal, Shawa, Isaac Thom, Shawkat, Ahmed, Shawky, Nehal, Shehata, Osama, Sheils, Sinead, Shewaye, Abate Bane, Shi, Guojun, Shi, Junping, Shimose, Shigeo, Shirono, Tomotake, Shou, Lan, Shrestha, Ananta, Shui, Guanghou, Sievert, William, Sigurdardottir, Solveig, Sira, Mostafa Mohamed, Siradj, Riyadh, Sison, Cecilia, Smyth, Linda, Soliman, Reham, Sollano, Jose D, Sombie, Roger, Sonderup, Mark, Sood, Siddharth, Soriano, German, Stedman, Catherine A M, Stefanyuk, Oksana, Štimac, Davor, Strasser, Simone, Strnad, Pavel, Stuart, Katherine, Su, Wen, Su, Minghua, Sumida, Yoshio, Sumie, Shuji, Sun, Dan-Qin, Sun, Jing, Suzuki, Hiroyuki, Svegliati-Baroni, Gianluca, Swar, Mohamed Osman, TAHARBOUCHT, S., Taher, Zenab, Takamura, Saori, Tan, Lin, Tan, Soek-Siam, Tanwandee, Tawesak, Tarek, Sara, Tatiana, Ghelimici, Tavaglione, Federica, Tecson, Gina Y., Tee, Hoi-Poh, Teschke, Rolf, Tharwat, Mostafa, Thong, Vo Duy, Thursz, Mark, Tine, Tulari, Tiribelli, Claudio, Tolmane, Ieva, Tong, Jing, Tongo, Marco, Torkie, Mamdouh, Torre, Aldo, Torres, Esther A, Trajkovska, Meri, Treeprasertsuk, Sombat, Tsutsumi, Tsubasa, Tu, Thomas, Tur, Josep A., Turan, Dilara, Turcan, Svetlana, Turkina, Svetlana, Tutar, Engin, Tzeuton, Christian, Ugiagbe, Rose, Uygun, Ahmet, Vacca, Michele, Vajro, Pietro, Van der Poorten, David, Van Kleef, Laurens A., Vashakidze, Eliza, Velazquez, Carlos Moctezuma, Velazquez, Mirtha Infante, Vento, Sandro, Verhoeven, Veronique, Vespasiani-Gentilucci, Umberto, Vethakkan, Shireene Ratna, Vilaseca, Josep, Vítek, Libor, Volkanovska, Ance, Wallace, Michael, Wan, Wang, Wang, Yan, Wang, Ying, Wang, Xiaolin, Wang, Xuemei, Wang, Chengyan, Wang, Chunjiong, Wang, Mingjie, Wangchuk, Pelden, Weltman, Martin, White, MaryFrances, Wiegand, Johannes, Wifi, Mohamed-Naguib, Wigg, Alan, Wilhelmi, Markus, William, Remon, Wittenburg, Henning, Wu, Shengjie, Wubeneh, Abdu Mohammed, Xia, Hongping, Xiao, Jian, Xiao, Xiao, Xiaofeng, Wang, Xiong, Wanyuan, Xu, Liang, Xu, Jie, Xu, Weiguo, Xu, Jing-Hang, Xu, Keshu, Xu, Yumin, Xu, Shi-Hao, Xu, Meng, Xu, Aimin, Xu, Chengfu, Yan, Hongmei, Yang, Jingyi, Yang, Rui-Xu, Yang, Yating, Yang, Qinhe, Yang, Naibin, Yao, Jia, Yara, Justine, Yaraş, Serkan, Yılmaz, Nimet, Younes, Ramy, younes, Huda, Young, Sona, Youssef, Farah, Yu, Yanyan, Yu, Ming-Lung, Yuan, Jing, Yue, Zhang, Yuen, Man-Fung, Yun, Wang, Yurukova, Nonka, Zakaria, Serag, Zaky, Samy, Zaldastanishvili, Maia, Zapata, Rodrigo, Zare, Nazanin, Zerem, Enver, Zeriban, Nema, Zeshuai, Xu, Zhang, Huijie, Zhang, Xuemei, Zhang, Yupei, Zhang, Wen-Hua, Zhang, Xuchen, Zhang, Yon-ping, Zhang, Yuexin, Zhang, Zhan-qing, Zhao, Jingmin, Zhao, Rong-Rong, Zhao, Hongwei, Zheng, Chao, Zheng, Yijie, Zheng, Ruidan, Zheng, Tian-Lei, Zheng, Kenneth, Zhou, Xi Qiao, Zhou, Yongjian, Zhou, Yu-Jie, Zhou, Hong, Zhou, Ling, Zhou, Yongning, Zhu, Long dong, Zhu, Yong Fen, Zhu, Yueyong, Zhu, Pei-Wu, Ziada, Ebtesam, Ziring, David, Ziyi, Li, Zou, Shanshan, Zou, Zhengsheng, Zou, Huaibin, and Zuart Ruiz, Roberto
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- 2022
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29. Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C in Taiwan: Real-world data
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Hong, Chun-Ming, Liu, Chen-Hua, Su, Tung-Hung, Yang, Hung-Chih, Chen, Pei-Jer, Chen, Yu-Wen, Kao, Jia-Horng, and Liu, Chun-Jen
- Abstract
Treatment of chronic hepatitis C (CHC) has entered a new era since the introduction of direct-acting antiviral agents (DAAs). Numerous clinical trials have shown that treatment response as well as tolerability of DAAs are superior to those of conventional therapy with pegylated interferon and ribavirin. However, the results of clinical trials may not be directly applied to real-world practice. Therefore our study tried to investigate the effectiveness of various DAA regimens in Taiwanese patients with chronic hepatitis C.
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- 2020
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30. Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy
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Tseng, Tai-Chung, Peng, Cheng-Yuan, Hsu, Yao-Chun, Su, Tung-Hung, Wang, Chia-Chi, Liu, Chun-Jen, Yang, Hung-Chih, Yang, Wan-Ting, Lin, Chia-Hsin, Yu, Ming-Lung, Lai, Hsueh-Chou, Tanaka, Yasuhito, Nguyen, Mindie H., Liu, Chen-Hua, Chen, Pei-Jer, Chen, Ding-Shinn, and Kao, Jia-Horng
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Background and Aims:Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker correlating with liver fibrosis stages. However, little is known about how it predicts risks of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term antiviral treatment. Materials and Methods:The study contained 2 parts. The first part was to explore whether M2BPGi could be an HCC predictor in 899 CHB patients receiving long-term entecavir therapy. The second part was to validate the findings in an independent cohort of 384 on-treatment CHB patients with more severe liver disease. Results:In the discovery cohort, there were 64 patients developing HCC within an average follow-up of 7.01 years. Our data showed that M2BPGi level was positively associated with HCC development. When stratifying the patients by an M2BPGi level of 1.73 (the third quartile), the high M2BPGi group was shown to have an increased HCC risk compared to the low M2BPGi group with hazard ratio of 5.80 (95% CI 3.50–9.60). Furthermore, we found that the M2BPGi level complements PAGE-B score, a well-validated HCC prediction model, to predict HCC development. Lastly, the cutoff was validated in the independent cohort, especially those with an intermediate PAGE-B score. Conclusions:In CHB patients receiving long-term antiviral treatment, serum M2BPGi level not only serves as an independent HCC predictor but also complements PAGE-B in stratifying HCC risks.
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- 2020
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31. A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
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Zhang, Tian-Ying, Guo, Xue-Ran, Wu, Yang-Tao, Kang, Xiao-Zhen, Zheng, Qing-Bing, Qi, Ruo-Yao, Chen, Bin-Bing, Lan, Ying, Wei, Min, Wang, Shao-Juan, Xiong, Hua-Long, Cao, Jia-Li, Zhang, Bao-Hui, Qiao, Xiao-Yang, Huang, Xiao-Fen, Wang, Ying-Bin, Fang, Mu-Jin, Zhang, Ya-Li, Cheng, Tong, Chen, Yi-Xin, Zhao, Qin-Jian, Li, Shao-Wei, Ge, Sheng-Xiang, Chen, Pei-Jer, Zhang, Jun, Yuan, Quan, and Xia, Ning-shao
- Abstract
ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.
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- 2020
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32. Efficacy and safety of 12 weeks of daclatasvir, asunaprevir plus ribavirin for HCV genotype-1b infection without NS5A resistance-associated substitutions.
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Yu, Ming-Lung, Hung, Chao-Hung, Huang, Yi-Hsiang, Peng, Cheng-Yuan, Lin, Chun-Yen, Cheng, Pin-Nan, Chien, Rong-Nan, Hsu, Shih-Jer, Liu, Chen-Hua, Huang, Chung-Feng, Su, Chien-Wei, Huang, Jee-Fu, Liu, Chun-Jen, Kao, Jia-Horng, Chuang, Wan-Long, Chen, Pei-Jer, and Chen, Ding-Shinn
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RIBAVIRIN ,HEPATITIS C virus ,HEPATITIS C ,ANTIVIRAL agents ,COMBINATION drug therapy ,CLINICAL trials ,DRUG resistance in microorganisms ,HEPATITIS viruses ,IMIDAZOLES ,ISOQUINOLINE ,LONGITUDINAL method ,MEDICAL cooperation ,PROTEINS ,RESEARCH ,RNA ,SULFONAMIDES ,CHRONIC hepatitis C ,THERAPEUTICS - Abstract
Background/purpose: Treatment with daclatasvir plus asunaprevir (DCV + ASV) for 24 weeks provided a sustained virologic response (SVR) rate of over 90% in hepatitis C virus genotype 1b (HCV-1b) infected patients without non-structural 5A (NS5A) resistance-associated substitutions (RASs) at the L31 and Y93 sites. In this study, we investigated whether adding ribavirin to the DCV + ASV combination could shorten the original treatment regimen to 12 weeks without compromising the treatment efficacy for HCV-1b patients without NS5A RASs.Methods: In the prospective, open-label, single-arm, nationwide multi-center phase III study, a total of 70 interferon-naïve or interferon-experienced HCV-1b patients without baseline L31/Y93 RASs received daclatasvir (60 mg/day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks, with a 12-week post-treatment follow-up. The primary end-point was the rate of undetectable HCV RNA 12 weeks post-treatment (SVR12).Results: The SVR12 rate was 97.1% (68/70) and 100% (68/68) in the full-analysis-set and the per-protocol population, respectively. None of the 68 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. Two patients withdrew from the study at treatment days 21 and 34 due to anorexia and fatigue, which were considered ribavirin-related and resolved post medication cessation. A total of 4 serious adverse events were reported and considered treatment-unrelated. No deaths or grade 4 adverse events requiring hospitalization was observed throughout the study.Conclusion: Truncated regimen of DCV + ASV plus ribavirin for 12 weeks was highly effective and safe in HCV-1b patients without NS5A L31/Y93 RAS. [ABSTRACT FROM AUTHOR]- Published
- 2019
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33. Cell and Animal Models for Studying Hepatitis B Virus Infection and Drug Development.
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Hu, Jianming, Lin, You-Yu, Chen, Pei-Jer, Watashi, Koichi, and Wakita, Takaji
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Many cell culture and animal models have been used to study hepatitis B virus (HBV) replication and its effects in the liver; these have facilitated development of strategies to control and clear chronic HBV infection. We discuss the advantages and limitations of systems for studying HBV and developing antiviral agents, along with recent advances. New and improved model systems are needed. Cell culture systems should be convenient, support efficient HBV infection, and reproduce responses of hepatocytes in the human body. We also need animals that are fully permissive to HBV infection, convenient for study, and recapitulate human immune responses to HBV and effects in the liver. High-throughput screening technologies could facilitate drug development based on findings from cell and animal models. [ABSTRACT FROM AUTHOR]
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- 2019
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34. Taiwan consensus statement on the management of chronic hepatitis B.
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Chien, Rong-Nan, Kao, Jia-Horng, Peng, Cheng-Yuan, Chen, Chien-Hung, Liu, Chun-Jen, Huang, Yi-Hsiang, Hu, Tsung-Hui, Yang, Hwa-I, Lu, Sheng-Nan, Ni, Yen-Hsuan, Chuang, Won-Long, Lee, Chuan-Mo, Wu, Jaw-Chin, Chen, Pei-Jer, and Liaw, Yun-Fan
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CHRONIC hepatitis B ,IMMUNOSUPPRESSION ,HEPATITIS B ,MATERNAL age ,TRANSPLANTATION of organs, tissues, etc. ,THERAPEUTIC use of proteins ,HEPATITIS B vaccines ,ANTIVIRAL agents ,CONSENSUS (Social sciences) ,HEPATITIS viruses ,HEPATOCELLULAR carcinoma ,HIV infections ,IMMUNIZATION ,CIRRHOSIS of the liver ,LIVER tumors ,MEDICAL protocols ,MEDICAL societies ,PROTEINS ,PURINES ,QUESTIONNAIRES ,VIRAL antigens ,DISEASE management ,VIRAL load ,DISEASE progression ,DISEASE complications ,DIAGNOSIS ,PREVENTION ,VACCINES ,THERAPEUTICS - Abstract
The experts of Taiwan Association for the Study of Liver (TASL) have actively participated and led the guidelines on hepatitis B virus (HBV) management by Asian Pacific Association for the Study of Liver (APASL) which is the first international association for the study of liver to publish the statement on HBV management before. However, there are more and more new data on the natural history and treatment of HBV infection in the past decade. These include new application of an old biomarker (quantitative HBsAg), clinical significance of HBV genotype and naturally occurring mutations, the role of non-invasive examination in evaluating severity of hepatic fibrosis, clinical significance of outcome calculators, new drug or new combination strategies towards more effective therapy and organ transplantation including liver and non-liver transplantation. It is time to publish the guidelines on HBV management of Taiwan. Hence, TASL have conducted an expert meeting to review, to discuss and to debate the relevant literatures, followed by draft the manuscript of HBV management guidelines and recommendations. The guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patient receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included. [ABSTRACT FROM AUTHOR]
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- 2019
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35. Low Hepatitis B Core–Related Antigen Levels Correlate Higher Spontaneous Seroclearance of Hepatitis B Surface Antigen in Chronic Hepatitis B Patients With High Hepatitis B Surface Antigen Levels.
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Tseng, Tai-Chung, Chiang, Chieh, Liu, Chun-Jen, Hong, Chun-Ming, Su, Tung-Hung, Yang, Hung-Chih, Yang, Wan-Ting, Liu, Chen-Hua, Chen, Pei-Jer, and Kao, Jia-Horng
- Abstract
Seroclearance of hepatitis B surface antigen (HBsAg) indicates functional cure for hepatitis B virus (HBV) infection. Low HBsAg levels can predict HBsAg seroclearance over time. However, little is known about the association between hepatitis B core–related antigen (HBcrAg) levels and spontaneous seroclearance of HBsAg. We conducted a retrospective cohort study including 2614 treatment-naïve patients with chronic HBV infection who received long-term follow-up at the National Taiwan University Hospital. The primary end point was spontaneous HBsAg seroclearance. We aimed to explore whether HBcrAg levels could predict HBsAg seroclearance, especially for patients with HBsAg levels >1000 IU/mL. There were 465 patients who cleared HBsAg with 32,414.72 person-years of follow-up, with a mean clearance rate of 1.43% per year. We found that lower HBcrAg levels at baseline were associated with an increased likelihood of HBsAg seroclearance (log rank P <.001). When restricting the study population to 1539 patients with HBsAg levels >1000 IU/mL, only HBcrAg <10,000 U/mL (vs ≥100,000 U/mL) served as an independent viral predictor for HBsAg seroclearance, with adjusted hazard ratio of 1.95 (95% CI, 1.16–3.27). In contrast to the late decline of HBsAg levels (5–9 years before HBsAg seroclearance), HBcrAg levels became undetectable 10–14 years before HBsAg seroclearance. This finding was confirmed by the different annual HBsAg seroclearance rates in the first and second decades of follow-up (0.97% vs 3.75%; P <.001) in patients achieving undetectable HBcrAg levels. Lower serum HBcrAg levels were associated with increased probability of HBsAg seroclearance over time. In patients with HBsAg levels >1000 IU/mL, clearing HBcrAg may serve as an early biomarker for HBsAg seroclearance. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2023
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36. Impact of occult hepatitis B on the clinical outcomes of patients with chronic hepatitis C virus infection: A 10-year follow-up.
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Chen, Hsing-Yu, Su, Tung-Hung, Tseng, Tai-Chung, Yang, Wan-Ting, Chen, Ting-Chih, Chen, Pei-Jer, Chen, Ding-Shinn, Kao, Jia-Horng, and Liu, Chun-Jen
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HEPATITIS B virus ,HEPATITIS C ,HEALTH outcome assessment ,LIVER cancer ,DISEASE progression ,CELL surface antigens ,PATIENTS - Abstract
Background/purpose: Occult hepatitis B infection (OHB) is not rare in countries that are endemic for hepatitis B virus (HBV) and in patients with chronic hepatitis C virus (HCV) infection. Notably, OHB has been shown to play a role in the progression of liver diseases, including the development of hepatocellular carcinoma (HCC); however, the data is inconsistent. We aim to clarify the contribution of concurrent OHB to the progression of liver diseases in a long-term cohort of patients with HCV infection and to investigate the value of total anti-hepatitis B core (anti-HBc) antibody as a surrogate OHB biomarker.Methods: We included 250 chronic anti-HCV-positive patients who had resolved HBV infection (anti-HBc positive and hepatitis B surface antigen negative). OHB was then detected using a sensitive commercial assay for serum HBV DNA with a low limit of detection of 6 IU/mL. Clinical outcomes, including the development of liver cirrhosis, HCC, and all-cause deaths, were compared between OHB-positive and OHB-negative patients.Results: At baseline, only 183 (73.20%) patients had positive HCV ribonucleic acid, and 56 (30.60%) of these 183 patients with active HCV infection had OHB. The presence of OHB did not correlate with any adverse clinical outcome in multivariate analyses. In addition, chronic hepatitis C patients with OHB did not have a higher level of serum total anti-HBc.Conclusion: OHB infection may not contribute to the development of adverse liver outcomes in patients with chronic HCV. [ABSTRACT FROM AUTHOR]- Published
- 2017
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37. Addition of ribavirin to daclatasvir plus asunaprevir for chronic hepatitis C 1b patients with baseline NS5A resistance-associated variants improved response.
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Chun-Ming Hong, Chun-Jen Liu, Shiou-Hwei Yeh, Pei-Jer Chen, Hong, Chun-Ming, Liu, Chun-Jen, Yeh, Shiou-Hwei, and Chen, Pei-Jer
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RIBAVIRIN ,CHRONIC hepatitis C ,HEPATITIS C treatment ,ANTIVIRAL agents ,INTERFERON receptors ,THERAPEUTICS ,IMIDAZOLES ,ISOQUINOLINE ,SULFONAMIDES ,COMBINATION drug therapy ,DRUG resistance in microorganisms ,GENETIC polymorphisms ,HEPATITIS viruses ,CIRRHOSIS of the liver ,PROTEINS ,VIRAL load ,GENOTYPES - Abstract
Background/purpose: Daclatasvir is a nonstructural protein 5A inhibitor with potent activity against hepatitis C virus genotypes 1-6 in vitro, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate, the SVR rate in patients with baseline NS5A-L31/Y93H polymorphisms decreased to around 40%. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important. Whether the addition of ribavirin could improve the SVR rate among this group of patients remains unknown and hence our case series was reported.Methods: For six adult chronic hepatitis C 1b patients with a pre-existing NS5A-Y93H (>20%) polymorphism, we added ribavirin (800 mg/d) to daclatasvir/asunaprevir for 24 weeks and followed through 12-weeks post-treatment. Four of these patients received interferon/ribavirin treatment before but relapsed, while the other two were naïve cases. Two of them had liver cirrhosis and one had hepatocellular carcinoma postcurative therapy. The primary efficacy end-point was undetectable hepatitis C virus RNA (hepatitis C virus RNA level of<25 IU/mL) at 12 weeks after the end of the treatment (SVR12).Results: In total, five cases reached SVR12 eventually (SVR rate: 83%; 95% confidence interval: 18.6-99.1%). However, the viral load of one remaining patient rebounded from the 24th week of treatment. No patients developed significant adverse effects during and after the treatment.Conclusion: In genotype 1b chronic hepatitis C patients with NS5A-Y93H polymorphism, the addition of ribavirin to daclatasvir/asunaprevir may increase the SVR12 rate with minimal side effects, and thus deserves more comprehensive trials in resource-limited areas. [ABSTRACT FROM AUTHOR]- Published
- 2017
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38. Long-term Evolution of Estimated Glomerular Filtration Rate in Patients With Antiviral Treatment for Hepatitis C Virus Infection.
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Liu, Chen-Hua, Lin, Jou-Wei, Liu, Chun-Jen, Su, Tung-Hung, Wu, Jo-Hsuan, Tseng, Tai-Chung, Chen, Pei-Jer, and Kao, Jia-Horng
- Abstract
Data regarding the long-term evolution of estimated glomerular filtration rate (eGFR) in patients receiving antiviral treatment for hepatitis C virus are limited. A total of 1987 patients with eGFR ≥15 mL/min/1.73m
2 who received interferon or direct-acting antiviral treatment were prospectively enrolled in this cohort study. The eGFR was assessed biannually by the Chronic Kidney Disease Epidemiology Collaboration equation from the time point of sustained virologic response (SVR 12). Multivariate generalized estimated equation was used to assess the association between the factors of interest and evolution of eGFR following antiviral treatment. Multivariate Cox regression analysis was used to assess the relative risk of end-stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m2 . Patients who achieved SVR 12 (adjusted slope coefficient difference: 2.36 mL/min/1.73 m2 /year; 95% confidence interval [CI], 1.50 to 3.32; P <.001) were associated with eGFR improvement, compared with those who did not achieve SVR 12. Among patients who achieved SVR 12 , the eGFR evolution was comparable (adjusted slope coefficient difference: 0.31 mL/min/1.73m2 /year; 95% CI, −0.34 to 0.96; P =.35) in those treated with interferon or direct-acting antiviral. The incidence rates of ESRD in patients who achieved and did not achieve SVR 12 were 0.06 per 100 person-years and 0.37 per 100 person-years. Patients who achieved SVR 12 were associated with a lower risk of ESRD (adjusted hazard ratio, 0.24; 95% CI, 0.05–0.68; P =.021). The long-term eGFR evolution and risk of ESRD are significantly improved in patients who achieve SVR 12 with anti- hepatitis C virus treatment. [Display omitted] [ABSTRACT FROM AUTHOR]- Published
- 2023
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39. Prevalence and clinical implications of IL28B genotypes in Taiwanese patients with chronic hepatitis C.
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Yone-Han Mah, Chen-Hua Liu, Chi-Ling Chen, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao, Mah, Yone-Han, Liu, Chen-Hua, Chen, Chi-Ling, Tseng, Tai-Chung, Liu, Chun-Jen, Chen, Pei-Jer, Chen, Ding-Shinn, and Kao, Jia-Horng
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CHRONIC hepatitis B ,GENOTYPES ,BIOPSY ,HISTOLOGICAL techniques ,VIRAL hepatitis ,GENETICS - Abstract
Background/purpose: Clinical implications of IL28B gene in Taiwanese chronic hepatitis C (CHC) patients remain unknown. We thus investigated the prevalence and clinical implications of IL28B rs8099917 genotypes in CHC patients with different hepatitis C virus (HCV) genotypes and healthy controls.Methods: A total of 200 HCV genotype 1 patients and 200 HCV genotype 2 patients who received liver biopsy, as well as 197 healthy controls were enrolled to determine the frequencies of IL28B rs8099917 genotypes. In addition, the association of IL28B rs8099917 genotype with baseline data, including HCV RNA level, HCV genotype, histological activity grade, fibrosis stage, and body mass index, were evaluated and further stratified by covariant factors.Results: Compared with healthy controls, CHC patients had a lower prevalence rate of favorable IL28B rs8099917 TT genotype (81.0% vs. 89.3%, p = 0.025). In addition, the prevalence rates of favorable TT genotype in patients with HCV genotypes 1 and 2 were 76.0% and 86.0%, respectively (p = 0.007). Using ordered logistic regression analysis, higher fibrosis stages were found to be associated with a lower prevalence of TT genotype (p = 0.033), but not histological activity grades (p = 0.748). The association with fibrosis stages was more pronounced in female patients (p = 0.024).Conclusion: In Taiwan, CHC patients have a lower frequency of favorable IL28B TT genotype than healthy controls. Among patients with CHC, the frequency of TT genotype is higher in HCV genotype 2 patients than in HCV genotype 1 patients. In addition, CHC patients with TT genotype, particularly females, have a lower likelihood of advanced fibrosis. [ABSTRACT FROM AUTHOR]- Published
- 2016
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40. Association Between High Levels of Hepatitis B Core Antibody and Seroclearance of Hepatitis B e Antigen in Individuals With Chronic Hepatitis B Virus Infection.
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Liu, Jessica, Hu, Hui-Han, Chang, Chia-Ling, Jen, Chin-Lan, Lee, Mei-Hsuan, Lu, Sheng-Nan, Wang, Li-Yu, Yuan, Quan, Xia, Ning-Shao, Sugiyama, Masaya, Nishida, Nao, Mizokami, Masashi, Chen, Chien-Jen, Chen, Pei-Jer, and Yang, Hwai-I
- Abstract
For chronic hepatitis B patients, hepatitis B e antigen (HBeAg) seroclearance signals a transition from an immunologically active phase to an inactive carrier state with a reduction in hepatitis B virus (HBV) DNA levels and a reduced risk of hepatocellular carcinoma (HCC).
1 Predictors of HBeAg seroclearance include lower HBV DNA levels, viral genotype, the precore mutation, and higher serum alanine aminotransferase (ALT) levels.2 [ABSTRACT FROM AUTHOR]- Published
- 2019
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41. Acoustic Radiation Force Impulse US Imaging: Liver Stiffness in Patients with Chronic Hepatitis B with and without Antiviral Therapy
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Su, Tung-Hung, Liao, Chun-Hsun, Liu, Chen-Hua, Huang, Kai-Wen, Tseng, Tai-Chung, Yang, Hung-Chih, Liu, Chun-Jen, Chen, Pei-Jer, Chen, Ding-Shinn, and Kao, Jia-Horng
- Abstract
Long-term antiviral therapy reduces liver stiffness in chronic hepatitis B as measured by serial acoustic radiation force impulse US measurement.
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- 2018
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42. Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection
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Lin, Pin-Hung, Wong, Weng-In, Wang, Yi-Lan, Hsieh, Meng-Ping, Lu, Chia-wen, Liang, Chieh-Yu, Jui, Sung-Hsiang, Wu, Fang-Yi, Chen, Pei-Jer, and Yang, Hung-Chih
- Abstract
Peptide-based T cell vaccines targeting the conserved epitopes of influenza virus can provide cross-protection against distantly related strains, but they are generally not immunogenic. Foreign antigen-specific regulatory T (Treg) cells are induced under subimmunogenic conditions peripherally, although their development and role in vaccine-mediated antiviral immunity is unclear. Here, we demonstrated primary vaccination with peptides alone significantly induced antigen-specific Foxp3+Treg cells, which were further expanded by repeated vaccination with unadjuvanted peptides. Certain adjuvants, including CpG, suppressed the induction and expansion of antigen-specific Treg cells by peptide vaccination. Interestingly, secondary influenza virus infection significantly increased the frequency of preexisting antigen-specific Treg cells, although primary infection barely induced them. Importantly, specific depletion of vaccine-induced antigen-specific Treg cells promoted influenza viral clearance, indicating their inhibitory role in vivo. Immunization with CpG-adjuvanted peptides by the subcutaneous prime–intranasal-boost strategy restricted the recruitment and accumulation of antigen-specific Treg cells in lung, and stimulated robust T cell immunity. Finally, subcutaneous prime–intranasal-boost immunization with CpG-adjuvanted peptides or whole-inactivated influenza vaccines protected mice from heterosubtypic influenza virus infection. In conclusion, antigen-specific Treg cells induced by peptide vaccines attenuate the antiviral immunity against influenza virus infection. CpG-adjuvanted peptide vaccines provide heterosubtypic influenza protection probably by inhibiting Treg development and enhancing T cell immunity.
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- 2018
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43. Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection
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Lin, Pin-Hung, Wong, Weng-In, Wang, Yi-Lan, Hsieh, Meng-Ping, Lu, Chia-wen, Liang, Chieh-Yu, Jui, Sung-Hsiang, Wu, Fang-Yi, Chen, Pei-Jer, and Yang, Hung-Chih
- Abstract
Peptide-based T cell vaccines targeting the conserved epitopes of influenza virus can provide cross-protection against distantly related strains, but they are generally not immunogenic. Foreign antigen-specific regulatory T (Treg) cells are induced under subimmunogenic conditions peripherally, although their development and role in vaccine-mediated antiviral immunity is unclear. Here, we demonstrated primary vaccination with peptides alone significantly induced antigen-specific Foxp3+Treg cells, which were further expanded by repeated vaccination with unadjuvanted peptides. Certain adjuvants, including CpG, suppressed the induction and expansion of antigen-specific Treg cells by peptide vaccination. Interestingly, secondary influenza virus infection significantly increased the frequency of preexisting antigen-specific Treg cells, although primary infection barely induced them. Importantly, specific depletion of vaccine-induced antigen-specific Treg cells promoted influenza viral clearance, indicating their inhibitory role in vivo. Immunization with CpG-adjuvanted peptides by the subcutaneous prime–intranasal-boost strategy restricted the recruitment and accumulation of antigen-specific Treg cells in lung, and stimulated robust T cell immunity. Finally, subcutaneous prime–intranasal-boost immunization with CpG-adjuvanted peptides or whole-inactivated influenza vaccines protected mice from heterosubtypic influenza virus infection. In conclusion, antigen-specific Treg cells induced by peptide vaccines attenuate the antiviral immunity against influenza virus infection. CpG-adjuvanted peptide vaccines provide heterosubtypic influenza protection probably by inhibiting Treg development and enhancing T cell immunity.
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- 2018
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44. Intracellular hepatitis B virus increases hepatic cholesterol deposition in alcoholic fatty liver via hepatitis B core protein[S]
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Wang, Yaqi, Wu, Ting, Hu, Danqing, Weng, Xinxin, Wang, Xiaojing, Chen, Pei-Jer, Luo, Xiaoping, Wang, Hongwu, and Ning, Qin
- Abstract
Hepatitis B virus (HBV) infection is a prevalent infectious disease with serious outcomes like chronic and acute hepatitis, cirrhosis, and hepatocellular carcinoma. However, the metabolic alteration by HBV is rarely taken into consideration. With the high prevalence of alcohol consumption and chronic HBV infection, their overlap is assumed to be an increasing latent hazard; although the extent has not been calculated. Moreover, the impact of chronic alcohol consumption combined with HBV on cholesterol metabolism is unknown. Six-week-old male FVB/Ncrl mice were hydrodynamically injected with a pGEM-4Z-1.3HBV vector and then fed an ethanol diet for 6 weeks. Serum biomarkers and liver histology, liver cholesterol levels, and cholesterol metabolism-related molecules were measured. In vitro assays with HBx, hepatitis B surface (HBs), or hepatitis B core (HBc) protein expression in HepG2 cells costimulated with ethanol were conducted to assess the cholesterol metabolism. HBV expression synergistically increased cholesterol deposition in the setting of alcoholic fatty liver. The increase of intrahepatic cholesterol was due to metabolic alteration in cholesterol metabolism, including increased cholesterol synthesis, decreased cholesterol degradation, and impaired cholesterol uptake. Overexpression of HBV component HBc, but not HBs or HBx, selectively promoted the hepatocellular cholesterol level.
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- 2018
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45. Fibrosis-4 Index Helps Identify HBV Carriers With the Lowest Risk of Hepatocellular Carcinoma
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Tseng, Tai-Chung, Liu, Chun-Jen, Su, Tung-Hung, Yang, Wan-Ting, Chen, Chi-Ling, Yang, Hung-Chih, Wang, Chia-Chi, Kuo, Stephanie Fang-Tzu, Liu, Chen-Hua, Chen, Pei-Jer, Chen, Ding-Shinn, and Kao, Jia-Horng
- Abstract
Objectives:Several viral and host risk factors have been used to predict risks of hepatocellular carcinoma (HCC) in patients with chronic infection of hepatitis B virus (HBV). However, little is known whether fibrosis-4 (FIB-4) index, a liver fibrosis biomarker, helps identify non-cirrhotic patients with the lowest HCC risk.Methods:A total of 2075 treatment-naive Taiwanese patients with chronic HBV infection were followed for an average period of 16.02 years. None of them had liver cirrhosis at baseline. We explored whether a low FIB-4 index complements the favourable predictors to defines patients with the lowest HCC risk. The finding was validated in 532 non-cirrhotic patients receiving long-term nucleos(t)ide analogue (NUC) treatment with suppressed viral replication.Results:A total of 137 treatment-naive and 10 NUC-treated patients developed HCC, respectively. We found that HCC risk started to increase when baseline FIB-4 index >1.29 in the treatment-naive cohort. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with a higher risk of HCC with hazards ratio of 5.56 (95% confidence interval: 3.93–7.86). More importantly, among patients with low viral load (HBV DNA level <2,000 IU/ml), baseline FIB-4 index helped stratify different HCC risks such that none of 326 HBeAg-negative patients with FIB-4 index <1.29, ALT level <40 U/l, and HBsAg level <1,000 IU/ml developed HCC. In addition, the patients with the FIB-4 index <1.29 consistently had the lowest HCC risks in the validation cohort receiving long-term NUC treatment.Conclusions:In non-cirrhotic patients with chronic HBV infection, FIB-4 index <1.29 complements the existing clinical profile to define patients with the lowest HCC risk.
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- 2017
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46. Androgen receptor functions in pericentral hepatocytes to decrease gluconeogenesis and avoid hyperglycemia and obesity in male mice.
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Chen, Kai-Wei, Chen, Yu-Shan, Chen, Pei-Jer, and Yeh, Shiou-Hwei
- Subjects
HYPERGLYCEMIA ,ANDROGEN receptors ,NON-alcoholic fatty liver disease ,GLUCONEOGENESIS ,LIVER cells ,BLOOD sugar ,BODY weight - Abstract
Although the impact of hepatic androgen receptor (AR) pathway on liver pathogenesis was documented, its physiological function in normal liver is remained unclear. This study aims to investigate if hepatic AR acts on metabolism, the major liver function, using a hepatic-specific AR-transgenic (H-ARTG) mouse model. We established the albumin promoter driven H-ARTG mice and included wild type (WT) and H-ARKO mice for study. The body weight, specific metabolic parameters and results from various tolerance tests were compared in different groups of mice fed a chow diet, from 2 to 18 months of age. Glucose feeding and insulin treatment were used to study the expression and zonal distribution pattern of AR and related genes in liver at different prandial stages. The body weight of H-ARTG mice fed a chow diet was 15 % lower than that of wild-type mice, preceded by lower blood glucose and liver triglyceride levels caused by AR reduced hepatic gluconeogenesis. The opposite phenotypes identified in H-ARKO and castrated H-ARTG mice support the critical role of activated AR in decreasing gluconeogenesis and triglyceride levels in liver. Hepatic AR acting by enhancing the expression of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH), a key of glycerophosphate shuttle, was identified as one mechanism to decrease gluconeogenesis from glycerol. We further found AR normally expressed in zone 3 of hepatic lobules. Its level fluctuates dependent on the demand of glucose, decreased by fasting but increased by glucose uptake or insulin stimulation. AR is a newly identified zone 3 hepatic gene with function in reducing blood glucose and body weight in mice. It suggests that stabilization of hepatic AR is a new direction to prevent hyperglycemia, obesity and nonalcoholic fatty liver disease (NAFLD) in males. [Display omitted] • Overexpression of hepatic AR decreases body weight and white adipose tissues in male mice fed a chow diet. • Hepatic AR downregulates gluconeogenesis to decrease blood glucose and liver triglyceride, preceding body weight changes. • Increasing cGPDH in glycerophosphate shuttle is one mechanism for hepatic AR to decrease glycerol gluconeogenesis. • AR normally expresses in zone 3 hepatocytes and is decreased by fasting and restored postprandially by insulin stimulation. [ABSTRACT FROM AUTHOR]
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- 2022
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47. Perspectives on dual hepatitis B and C infection in Taiwan.
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Liu, Chun-Jen, Chen, Pei-Jer, Chen, Ding-Shinn, Tseng, Tai-Chung, and Kao, Jia-Horng
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HEPATITIS B virus ,HEPATITIS C virus ,VIRAL transmission ,LIVER diseases ,HEPATITIS associated antigen ,CIRRHOSIS of the liver ,HEPATITIS C treatment ,PATIENTS ,DISEASE risk factors ,THERAPEUTIC use of proteins ,RECOMBINANT proteins ,RIBAVIRIN ,ANTIVIRAL agents ,POLYETHYLENE glycol ,COMBINATION drug therapy ,HEPATITIS B ,HEPATITIS C ,HEPATITIS viruses ,VIRAL antigens ,TREATMENT effectiveness ,GENOTYPES ,MIXED infections ,THERAPEUTICS - Abstract
Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas, and can be found in populations at risk of parenteral viral transmission. Clinical observatory studies suggest a higher risk of liver disease progression in patients with dual HCV/HBV infection than in HBV or HCV monoinfected patients. Recent trials confirmed that combination therapy of peginterferon alfa-2a or alfa-2b and ribavirin was effective and safe in dually infected patients with positive HCV RNA. Moreover, about 30% of the dually infected patients cleared hepatitis B surface antigen within 5 years after the start of peginterferon-based therapy. The optimal treatment strategies for dually infected patients with active hepatitis B, with decompensated cirrhosis, or in other clinical situations should be explored in further studies. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may lead to the development of strategies for the treatment of dually infected patients with active hepatitis C, particularly for those not tolerating or not eligible for peginterferon-based therapy. Notably, direct-acting antivirals would not have any activity against HBV infection; simultaneous or on-demand nucleos(t)ide analogs would be needed if clinically indicated. [ABSTRACT FROM AUTHOR]
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- 2016
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48. Management of hepatitis C virus infection in the Asia-Pacific region: an update
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Lim, Seng Gee, Aghemo, Alessio, Chen, Pei-Jer, Dan, Yock Young, Gane, Edward, Gani, Rino, Gish, Robert G, Guan, Richard, Jia, Ji Dong, Lim, Kieron, Piratvisuth, Teerha, Shah, Samir, Shiffman, Mitchell L, Tacke, Frank, Tan, Soek Siam, Tanwandee, Tawesak, Win, Khin Maung, and Yurdaydin, Cihan
- Abstract
The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high.
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- 2017
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49. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study
- Author
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Razavi-Shearer, Devin, Gamkrelidze, Ivane, Pan, Calvin, Jia, Jidong, Berg, Thomas, Gray, Richard, Lim, Young-Suk, Chen, Chien-Jen, Ocama, Ponsiano, Desalegn, Hailemichael, Abbas, Zaigham, Abdallah, Ayat, Aghemo, Alessio, Ahmadbekova, Sabohat, Ahn, Sang Hoon, Aho, Inka, Akarca, Ulus, Al Masri, Nasser, Alalwan, Abduljaleel, Alavian, Seyed, Al-Busafi, Said, Aleman, Soo, Alfaleh, Faleh, Alghamdi, Abdullah, Al-Hamoudi, Waleed, Aljumah, Abdulrahman, Al-Naamani, Khalid, Al-Rifai, Ahmad, Alserkal, Yousif, Altraif, Ibrahim, Amarsanaa, Jazag, Anderson, Motswedi, Andersson, Monique, Armstrong, Paige, Asselah, Tarik, Athanasakis, Kostas, Baatarkhuu, Oidov, Ben-Ari, Ziv, Bensalem, Aicha, Bessone, Fernando, Biondi, Mia, Bizri, Abdul Rahman, Blach, Sarah, Braga, Wornei, Brandão-Mello, Carlos, Brosgart, Carol, Brown, Kimberly, Brown, Robert, Jr, Bruggmann, Philip, Brunetto, Maurizia, Buti, Maria, Cabezas, Joaquin, Casanovas, Teresa, Chae, Chungman, Chan, Henry Lik Yuen, Cheinquer, Hugo, Chen, Pei-Jer, Cheng, Kent Jason, Cheon, Myeong-Eun, Chien, Cheng-Hung, Choudhuri, Gourdas, Christensen, Peer Brehm, Chuang, Wan-Long, Chulanov, Vladimir, Cisneros, Laura, Coffin, Carla, Contreras, Fernando, Coppola, Nicola, Cornberg, Markus, Cowie, Benjamin, Cramp, Matthew, Craxi, Antonio, Crespo, Javier, Cui, Fuqiang, Cunningham, Chris, Dalgard, Olav, De Knegt, Robert, De Ledinghen, Victor, Dore, Gregory, Drazilova, Sylvia, Duberg, Ann-Sofi, Egeonu, Steve, Elbadri, Mohammed, El-Kassas, Mohamed, El-Sayed, Manal, Estes, Chris, Etzion, Ohad, Farag, Elmobashar, Ferradini, Laurent, Ferreira, Paulo, Flisiak, Robert, Forns, Xavier, Frankova, Sona, Fung, James, Gane, Edward, Garcia, Virginia, García-Samaniego, Javier, Gemilyan, Manik, Genov, Jordan, Gheorghe, Liliana, Gholam, Pierre, Gish, Robert, Goleij, Pouya, Gottfredsson, Magnus, Grebely, Jason, Gschwantler, Michael, Guingane, Nanelin Alice, Hajarizadeh, Behzad, Hamid, Saeed, Hamoudi, Waseem, Harris, Aaron, Hasan, Irsan, Hatzakis, Angelos, Hellard, Margaret, Hercun, Julian, Hernandez, Javier, Hockicková, Ivana, Hsu, Yao-Chun, Hu, Ching-Chih, Husa, Petr, Janicko, Martin, Janjua, Naveed, Jarcuska, Peter, Jaroszewicz, Jerzy, Jelev, Deian, Jeruma, Agita, Johannessen, Asgeir, Kåberg, Martin, Kaita, Kelly, Kaliaskarova, Kulpash, Kao, Jia-Horng, Kelly-Hanku, Angela, Khamis, Faryal, Khan, Aamir, Kheir, Omer, Khoudri, Ibtissam, Kondili, Loreta, Konysbekova, Aliya, Kristian, Pavol, Kwon, Jisoo, Lagging, Martin, Laleman, Wim, Lampertico, Pietro, Lavanchy, Daniel, Lázaro, Pablo, Lazarus, Jeffrey V, Lee, Alice, Lee, Mei-Hsuan, Liakina, Valentina, Lukšić, Boris, Malekzadeh, Reza, Malu, Abraham, Marinho, Rui, Mendes-Correa, Maria Cássia, Merat, Shahin, Meshesha, Berhane Redae, Midgard, Håvard, Mohamed, Rosmawati, Mokhbat, Jacques, Mooneyhan, Ellen, Moreno, Christophe, Mortgat, Laure, Müllhaupt, Beat, Musabaev, Erkin, Muyldermans, Gaëtan, Naveira, Marcelo, Negro, Francesco, Nersesov, Alexander, Nguyen, Van Thi Thuy, Ning, Qing, Njouom, Richard, Ntagirabiri, Rénovat, Nurmatov, Zuridin, Oguche, Stephen, Omuemu, Casimir, Ong, Janus, Opare-Sem, Ohene, Örmeci, Necati, Orrego, Mauricio, Osiowy, Carla, Papatheodoridis, George, Peck-Radosavljevic, Markus, Pessoa, Mário, Pham, Trang, Phillips, Richard, Pimenov, Nikolay, Pincay-Rodríguez, Loreley, Plaseska-Karanfilska, Dijana, Pop, Cora, Poustchi, Hossein, Prabdial-Sing, Nishi, Qureshi, Huma, Ramji, Alnoor, Rautiainen, Henna, Razavi-Shearer, Kathryn, Remak, William, Ribeiro, Sofia, Ridruejo, Ezequiel, Ríos-Hincapié, Cielo, Robalino, Marcia, Roberts, Lewis, Roberts, Stuart, Rodríguez, Manuel, Roulot, Dominique, Rwegasha, John, Ryder, Stephen, Sadirova, Shakhlo, Saeed, Umar, Safadi, Rifaat, Sagalova, Olga, Said, Sanaa, Salupere, Riina, Sanai, Faisal, Sanchez-Avila, Juan F, Saraswat, Vivek, Sargsyants, Narina, Sarrazin, Christoph, Sarybayeva, Gulya, Schréter, Ivan, Seguin-Devaux, Carole, Seto, Wai-Kay, Shah, Samir, Sharara, Ala, Sheikh, Mahdi, Shouval, Daniel, Sievert, William, Simojoki, Kaarlo, Simonova, Marieta, Sinn, Dong Hyun, Sonderup, Mark, Sonneveld, Milan, Spearman, C Wendy, Sperl, Jan, Stauber, Rudolf, Stedman, Catherine, Sypsa, Vana, Tacke, Frank, Tan, Soek-Siam, Tanaka, Junko, Tergast, Tammo, Terrault, Norah, Thompson, Alexander, Thompson, Peyton, Tolmane, Ieva, Tomasiewicz, Krzysztof, Tsang, Tak-Yin, Uzochukwu, Benjamin, Van Welzen, Berend, Vanwolleghem, Thomas, Vince, Adriana, Voeller, Alexis, Waheed, Yasir, Waked, Imam, Wallace, Jack, Wang, Cong, Weis, Nina, Wong, Grace, Wong, Vincent, Wu, Jaw-Ching, Yaghi, Cesar, Yesmembetov, Kakharman, Yip, Terry, Yosry, Ayman, Yu, Ming-Lung, Yuen, Man-Fung, Yurdaydin, Cihan, Zeuzem, Stefan, Zuckerman, Eli, and Razavi, Homie
- Abstract
The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally.
- Published
- 2023
- Full Text
- View/download PDF
50. Safety and dose escalation of the targeted oncolytic adenovirus OBP-301 for refractory advanced liver cancer: Phase I clinical trial
- Author
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Heo, Jeong, Liang, Ja-Der, Kim, Chang Won, Woo, Hyun Young, Shih, I-Lun, Su, Tung-Hung, Lin, Zhong-Zhe, Yoo, So Young, Chang, Stanley, Urata, Yasuo, and Chen, Pei-Jer
- Abstract
OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 × 1012viral particles. The most common treatment-emergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.
- Published
- 2023
- Full Text
- View/download PDF
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