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( Massimo Colombo ),( Alessio Aghemo ),( Lin Liu ),( Robert H. Hyland ),( Chohee Yun ),( Diana M. Brainard ),( John G. Mchutchison ),( Sunjin Hwang ),( Marc Bourliere ),( Markus Peck-radosavljevic ),( 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Methods: Kidney transplant recipients with chronic GT1 or GT4 HCV infection, treatment-naive and treatment-experienced, with or without compensated cirrhosis were randomized 1:1 at 5 sites in Europe to receive LDV/SOF (90 mg/400 mg) for 12 or 24 weeks. Randomization was stratified by HCV genotype, treatment history and presence or absence of cirrhosis. Cirrhosis was determined by liver biopsy (Metavir score = 4 or Ishak score ≥5), Fibroscan® >12.5 kPa, or Fibrotest® >0.75 and APRI >2. A pretreatment creatinine clearance <40 mL/min was an exclusionary criterion. The primary endpoint was SVR12. Results: 114 patients were randomized and treated; median age was 53, 58% were male, 94% were white, 72% carried the non-CC IL28B allele, 91% had GT 1 infection, 69% were treatment-naive, and 15% had compensated cirrhosis. The median eGFR was 56ml/min (range 35-135ml/min). All 92 patients with SVR4 data available achieved SVR4 including a patient discontinuing treatment at Week 4 due to an AE. SAEs were reported in 12 (11%) patients; 3 were assessed as treatment related: syncope, pulmonary embolism, and blood creatinine increased. The most frequent AEs were headache (19%), asthenia (13%), and fatigue (10%). Conclusions: Administration of LDV/SOF for 12 or 24 weeks in patients with chronic HCV genotype 1 or 4 patients who have undergone kidney transplant was safe and highly effective with an SVR4 rate of 100%. Treatment was well-tolerated. SVR12 data for all patients will be presented.
( Michael Charlton ),( Michael Manns ),( Hadas Dvory-sobol ),( Evguenia Svarovskaia ),( Brian Doehle ),( Sarah Arterburn ),( Chohee Yun ),( Diana M. Brainard ),( John G. Mchutchison ),( Michael Miller 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Ledipasvir/sofosbuvir (LDV/SOF) with ribavirin (RBV) demonstrated high SVR rates in patients with chronic hepatitis C (HCV) genotype (GT) 1 or 4 infection who have decompensated cirrhosis or who have undergone liver transplantation. Here we evaluated the effect of baseline HCV NS5A and NS5B resistance-associated variants (RAVs) on treatment outcome and characterized the viral resistance in all virologic failures. Methods: Deep sequencing with a 1% assay cut-off was performed for NS5A and NS5B at baseline for all the patients and at the time of virologic failure for those who relapsed. Results: Out of 625, 622, and 619 samples were analyzed for baseline NS5A and NS5B respectively. Table 1 summarizes SVR12 rates by treatment duration and the presence or absence of baseline NS5A RAVs. NS5B RAVs at baseline were uncommon, occurring in 4.8% (28/586) GT1 patients and 3.2% (1/31) GT 4 patients. Of these 29 patients, only one GT1 patient with CPT C cirrhosis who had L159F at baseline and was treated for 24 weeks with LDV/SOF+RBV did not achieve SVR12. NS5A RAVs at positions 24, 28, 30, 31, 58, and 93 were enriched or emerged in 20/22 (91%) GT1 and 1/3 GT4 infected patients with virologic failure. The NS5B NI RAV E237G emerged in 3 GT1a patients and 1 GT4d patient at the time of relapse (4/23, 17%). Conclusions: The presence of baseline NS5A or NS5B RAVs did not impact the treatment outcome to 12 or 24 weeks of LDV/SOF+RBV in GT1 or GT4 HCV patients with liver ransplantation without decompensated liver disease, or 24 weeks of LDV/SOF+RBV in patients with decompensated cirrhosis. Lower SVR rates were observed among the limited number of patients with decompensated cirrhosis and baseline NS5A RAVs who received 12 weeks of LDV/SOF+RBV treatment.
( S Fung ),( P Kwan ),( A Horban ),( M Pelemis ),( P Husa ),( H W Hann ),( Jf Flaherty ),( B Massetto ),( P Dinh ),( A Corsa ),( K Kitrinos ),( Jg Mchutchison ),( M Fabri ),( E Gane ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Efficacy and safety of tenofovir DF (TDF) have been demonstrated over 6 years in pivotal HBV studies, but have yet to be established in lamivudine-resistant (LAM-R) patients in a prospective, randomized trial. Methods: Phase 3b, double-blind, randomized (1:1) comparison of TDF and emtricitabine (FTC)/TDF in chronic HBV patients on LAM at screening with HBV DNA ≥103 IU/mL and documented LAM-R (rtM204V/I±rtL180M; INNO-LiPA HBV v2/ v3). Patients were stratified by ALT (≥ or <2×ULN) and HBeAg status. Efficacy and safety, including bone mineral density (BMD) monitoring by DXA were assessed over 96 weeks. Results: Of 280 randomized and treated patients, 133/141 (94%) and 125/139 (90%) in TDF and FTC/TDF groups completed 96 weeks. Groups were well matched: mean age 47 years, 75% males, 34% Asian, 47% HBeAg+, 42% ALT <ULN; HBV genotypes: 22% A, 14% B, 19% C, and 45% D. By ITT analysis, missing=failure, 89% and 86% receiving TDF and FTC/TDF, respectively, had HBV DNA <400 copies/mL at Week 96 (P =0.43); 70% in each arm had normal ALT. HBeAg loss was observed in 10/65 (15%) and 9/68 (13%) in TDF and FTC/TDF arms, respectively. One patient (FTC/TDF) had HBsAg loss without seroconversion. Both treatments were well tolerated with 1% (3/280) discontinuing for adverse event (1 TDF, 2 FTC/TDF). No patients had confirmed increase in serum creatinine of ≥0.5 mg/dL, and 1% (2 TDF) had serum phosphorus <2 mg/dL. BMD of spine and hip revealed no clinically relevant bone loss, and there were no non-traumatic fractures reported. No TDF resistance was detected through 96 weeks. Conclusions: A high rate of HBV DNA suppression with no detectable TDF resistance was achieved with TDF monotherapy in LAM?R patients through 96 weeks. TDF was safe and well tolerated, with a low rate of renal events and no evidence of clinically relevant bone loss.