Browsing by Author "Hsu, Shih-Jer"

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An Open-Label, Randomized, Active-Controlled Trial of 8 Versus 12 Weeks of Elbasvir/Grazoprevir for Treatment-Naive Patients With Chronic Hepatitis C Genotype 1b Infection and Mild Fibrosis (EGALITE Study): Impact of Baseline Viral Loads and NS5A Resistance-Associated Substitutions
(2019-08-15)
Huang, Chung-Feng
;
Hung, Chao-Hung
;
Cheng, Pin-Nan
;
Bair, Ming-Jong
;
Huang, Yi-Hsiang
Background. A 12-week grazoprevir/elbasvir regimen is highly effective against hepatitis C virus genotype 1 (HCV-1) infection. The efficacy of an 8-week regimen for treatment-naive HCV-1-infected patients with mild fibrosis has not been determined. Methods. Treatment-naive HCV-1b-infected patients with mild fibrosis were randomly assigned to receive 8 (n = 41) or 12 (n = 41) weeks of grazoprevir/elbasvir therapy. The primary end point was a sustained virologic response, defined as an HCV RNA level of < 12 IU/mL, at posttreatment week 12 (SVR12). Results. SVR12 was achieved by 87.8% of patients (36 of 41) in the 8-week arm and 100% (41 of 41) in the 8-week arm of the full-analysis population and by 90.0% (36 of 40) and 100% (41 of 41), respectively, in the per-protocol population (all P = .055). In the 8-week arm, a significantly lower SVR12 rate was observed among patients with a high HCV-1b load, defined as >= 1 500 000 IU/mL (79% vs 100%; P =.042), and among those with a baseline Y93H resistance-associated substitution (RAS) frequency of >15% in HCV nonstructural protein 5A (NS5A; 40.0% vs 97.1%; P = .004). Between-group analysis demonstrated that, among patient with a high HCV-1b load and a baseline Y93H RAS frequency of >15%, those in the 8-week arm had a substantially lower SVR12 rate than those in the 12-week arm (40.0% vs 100.0%). All 4 HCV-1b relapses had a Y93H RAS frequency of >99% at posttreatment week 12. Conclusions. Twelve weeks of grazoprevir/elbasvir therapy is highly effective for treatment-naive patients with mild fibrosis. A truncated, 8-week grazoprevir/elbasvir regimen might be applied for those with low viral loads or without a significant NS5A RAS frequency.
Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy
(2011-03-01)
Hsu, Ching-Sheng
;
Hsu, Shih-Jer
;
Chen, Hung-Chia
;
Tseng, Tai-Chung
;
Liu, Chen-Hua
Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN alpha-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 +/- 3.73) (day(-1), mean +/- SD) but lower daily viral production rate (P = 10(6)-10(12)) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients.
Association of IL28B genotypes with metabolic profiles and viral clearance rate in chronic hepatitis C patients
(2013-03-01)
Hsu, Ching-Sheng
;
Hsu, Shih-Jer
;
Chen, Hung-Chia
;
Liu, Chen-Hua
;
Jeng, Jenher
IL28B genotypes have a strong impact on treatment outcomes of chronic hepatitis C (CHC) and on-treatment viral kinetics. Since metabolic regulation and interferon response are highly integrated, metabolic profiles may play an important role in the link between IL28B genotypes and hepatitis C virus (HCV) infection. Thus, the association of IL28B rs8099917 genotypes with metabolic profiles and the impact of metabolic profiles on hepatitis C viral kinetic parameters were examined. A case-control analysis including 278 CHC patients and 280 subjects without chronic HCV infection was performed. The associations of IL28B rs8099917 genotype with pretreatment metabolic profiles and early viral kinetic parameters were evaluated. Compared to HCV genotype 1 patients, the differences in metabolic profiles were more significant in genotype 2 patients. HCV genotype 2 patients with TT genotype had higher serum total cholesterol and high density lipoprotein (HDL) levels than those with GT genotype, and the differences remained significant when adjusted for age, sex, and body mass index (p = 0.005 for total cholesterol; p = 0.006 for HDL). In addition, patients with higher serum TG, higher fasting blood glucose, and lower HDL had a lower viral clearance rate. IL28B genotypes may affect lipid profiles of CHC patients, especially in HCV-genotype 2 patients. Patients with higher serum fasting blood glucose, triglyceride, and lower HDL have a lower viral clearance rate during pegylated interferon plus ribavirin therapy.