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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

Frontiers of Medicine  2014, Vol. 8 Issue (2): 166-174   https://doi.org/10.1007/s11684-014-0334-2
  本期目录
Advances in newly developing therapy for chronic hepatitis C virus infection
Paul J. Pockros()
Division of Gastro/Hepatology, Scripps Clinic, 10666 N Torrey Pines Road, N203, La Jolla, CA 92067, USA
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Abstract

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

Key wordsdirect-acting antiviral (DAA)    nucleotide polymerase inhibitors    protease inhibitors
收稿日期: 2014-01-20      出版日期: 2014-05-21
 引用本文:   
. [J]. Frontiers of Medicine, 2014, 8(2): 166-174.
Paul J. Pockros. Advances in newly developing therapy for chronic hepatitis C virus infection. Front. Med., 2014, 8(2): 166-174.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-014-0334-2
https://academic.hep.com.cn/fmd/CN/Y2014/V8/I2/166
  
Class Study phase Proposed therapy Genotype studied Previous treatment Endpoint Percent achieving endpoint Adverse events
Asunaprevir NS3 PI II TRIPLE: 600 mg BID×12 weeks+
PEG-IFN /RBV for 24−48weeks
1 Naïve RVR at 4 and 12 weeks
SVR
eRVR in 75%
SVR in 83%
Hepatotoxicity
Simeprevir NS3/4A PI III TRIPLE: 150 mg daily×12 weeks+ PEG-IFN /RBV 1 Naïve SVR12 81% overall
65% in cirrhotics
Fatigue, headache, pruritis, hyperbilirubinemia, rash
III TRIPLE: 150?mg daily×12 weeks+ PEG-IFN /RBV 1 Relapse SVR12 79% overall, 70% genotype 1a and 86% 1b
Faldaprevir NS3/4A PI III TRIPLE: 120?mg a day vs. 240?mg a day vs. placebo×12?weeks+ PEG-IFN /RBV for 24?weeks 1 Naïve SVR12 79% at 120?mg dose
80% at 240?mg dose
Rash, photosensitivity, unconjugated hyperbilirubinemia, anemia
MK-5172 NS3/4A PI II 100?mg vs. 200?mg vs. 400?mg vs. 800?mg a day ×12weeks+ PEG-IFN / RBV ×24−48?weeks 1 Naïve SVR24 86% at 100 mg
92% at 200 mg
91% at 400 mg
87% at 800 mg
no effect of IL28B on SVR
Hyperbilirubinemia, elevated transaminases seen at higher doses.
Rash, anemia
Daclatasvir NS5A IIa 3?mg vs. 10?mg vs. 60?mg a day+ PEG-IFN /RBV ×48?weeks 1 Naïve RVR at 4 and 12 weeks 42% at 3?mg
83% at 10?mg
75% at 60?mg
Diarrhea, headache
Sofosbuvir NPI III 400?mg daily+ PEG-IFN /RBV 1, 4, 5, 6 Naïve SVR12 89% genotype 1
96% genotype 4
100% genotypes 5 and 6
Fatigue, headache, nausea and insomnia
400?mg daily+ RBV×12 weeks vs. PEG-IFN /RBV × 24?weeks 2, 3 Naïve SVR12 67% with sofosbuvir
67% with PEG-IFN /RBV
Mericitabine NPI II 1000?mg daily × 24 weeks+ PEG-IFN /RBV×24−48 weeks 1, 4 Naïve SVR12 56.8% vs. 36.5% mericitabine vs. placebo Fatigue, headache, nausea
Deleobuvir NNPI II 600?mg 3× a day+ PEG-IFN /RBV×28 days 1 Naïve RVR 58% GI events, rash, hyperbilirubinemia
VX-222 NNPI II 100?mg or 400?mg daily+
DUAL: telaprevir vs.
TRIPLE: tvr+ RBV
QUAD: tvr+ RBV+ IFN
1 Naïve RVR at 12 weeks 85% on 100?mg QUAD therapy
90% on 400?mg QUAD therapy
Fatigue, GI upset
Setrobuvir NNPI II 200?mg or 400?mg 2× a day+ PEG-IFN /RBV 1 Naïve SVR12 SVR equal between PEG-IFN /RBV and therapy with setrobuvir Rash
Tegobuvir NNPI II 40?mg 2× a day+
DUAL: GS-9256
TRIPLE: GS-9256/RBV
QUAD: GS-9256/ PEG-IFN /RBV
1 Naive RVR at 28?days 7% DUAL
38% TRIPLE
100% QUAD
Transient elevations in bilirubin
Tab.1  
  
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