Keywords: Hepatitis C virus; Chronic hepatitis C; Direct-acting antiviral agents
Hepatitis C virus (HCV) infection is one of the most common hepatic
diseases, which could pose a public health threat to the world. In China, there
are more than ten million patients infected by HCV [1]. The treatment system
for HCV infection has changed drastically over the past 5 years, direct-acting
antiviral agents (DAAs) has stepped onto the historical stage and experienced
unprecedented development with a real breakthrough [2,3]. In fact, when the
pegylated interferons α-ribavirin was widely used to treat HCV infection, we
have already realized that there was a possibility of being cured after
infected by HCV.
Although using the oral antiviral drugs has become the major treatment
option in most developed countries, DAAs are not available in China. The most
common treatment still based on the use of pegylated interferons α-ribavirin.
However, the cure rate of this treatment could only achieve 44% to 70% [4]. The
recurrence rate for genotype 1b could even reach 10%. And it also has many side
effects such as the long course of treatment, parenteral administration and the
complicated operation. Moreover, for many patients with nephrosis or severe cirrhosis,
such interferons are not allowed to be used. These limits towards interferons
greatly hindered the patient's recovery and cure. With the development of
economy, many of the domestic patients try to buy the DAAs from overseas in
various ways. Unfortunately, these purchasing channels could not ensure the
medicine quality, which could lead to the heavy potential safety hazard.
In 2016, the European Association for the Study
of the Liver (EASL) has completely entered the DAA age, and the pegylated
interferons α-ribavirin scheme was no longer recommended. The United States
Food and Drug Administration (FDA) has approved the following, currently
commercialised DAA:Sofosbuvir (Sovaldi) [5], Simeprevir (Olysio) [6],
Daclatasvir (Daklinza) [7], Sofosbuvir + ledipasvir (Harvoni) [8],
Ombitasvir-Paritaprevir/Ritonavir and dasabuvir (Viekirax) [9]. In the
meantime, drugs pending commercialization in the near future are combinations
of various antivirals.MSD (Merck Sharp and Dohme) combo: Grazoprevir (MK-5172),
100 mg, a second generation protease inhibitor, + Elbasvir (MK-8742), 50 mg, a
second generation NS5A inhibitor(10).BMS (Bristol-Myers Squibb) combo:
Asunaprevir+daclatasvir+beclabuvir: a combination of daclatasvir, asunaprevir
(NS3 protease inhibitor), and beclabuvir (a non-nucleoside NS5B polymerase
inhibitor) with activity in genotypes 1, 2, 3, 4 and 5; and variable activity
in genotype 6 [10,11]. The main inconvenience of these new drugs is their high
cost. This necessitates selection and prioritization of candidate patients to
receive them, via strategies established by the various national organizations,
in accordance with the recommendations of scientific societies. With the DAAs
appearing on the market, the anti-HCV therapy has gone into the late DAA epoch.
In this epoch, how to develop workable, practical as well as economical
anti-HCV therapy based on different patients individual need has become more
complicated and challengeable. In May
8th, 2018, Shanghai, Merck has announced that its polypillZepatier, the DAAs
towards HCV was approved by China's State Food and Drug Administration in April
28th, 2018. Zepatier is mainly used to cure the adult patients with chronic
hepatitis for genotype 1 and 4 [12]. Clinical
results showed that Zepatier has much higher sustained viral response (SVR).
For genotype 1, the SVR could increase from 94% to 98% after the treatment for
12 weeks. For genotype 4, the SVR could increase from 97% to 100%for 12 weeks
[13]. Nowadays, 56.8% the HCV infection patients was genotype 1b in China.
Zepatier would definitely bring the patients more options and more convenient
conditions for curing HCV infection [14].
Zepatieris
called as the “binary star” combination for curing HCV infection. It is a kind
of combination drug of elbasvir and grazoprevir. The patients should take one
pill every day for sustaining 12 weeks. This treatment would not need to
combine ribavirin, which provides a much more convenient therapeutic schedule
with only one single tablet. Meantime, for the HCV infection patients with
other diseases such as cirrhosis, HIV, advanced chronic kidney disease and
hereditary blood disease, Zepatier treatment could also get satisfactory
efficacy when combined with other common clinical drugs.
AUTHOR CONTRIBUTIONS
All authors have contributed to this article. YQLdrafted the full
manuscript and XG contributed in editing the manuscript.
COMPETING FINANCIAL
INTERESTS
The authors declare no competing financial
interests.
1.
Wei
L, Wang FS, Zhang MX, Jia JD, Yakovlev AA, et al. (2018) Daclatasvir plus
asunaprevir in treatment-naïve patients with hepatitis C virus genotype 1b
infection. World J Gastroenterol 24: 1361-1372.
2.
Jr
RSB (2016) The possible association between DAA
treatment for HCV infection and HCC recurrence.
Gastroenterol Hepatol 12: 776.
3.
El
MK, Funk AL, Salaheldin M, Shimakawa Y, Eltabbakh M, et al. (2017) Increased
recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C
infected Egyptian cohort: A comparative analysis. J Viral Hepat 25: 623-630.
4.
Zoulim
F, Liang TJ, Gerbes AL, Aghemo A, Deufficburban S, et al. (2015) Hepatitis C
virus treatment in the real world: Optimising treatment and access to
therapies. Gut 64: 1824-1833.
5.
Lawitz
E (2013) Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for
hepatitis C. New Eng J Med 368: 34.
6.
Manns
M, Marcellin P, Poordad F, de Araujo ES, Buti M, et al. (2014) Simeprevir with
pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients
with chronic hepatitis C virus genotype 1 infection (QUEST-2): A randomised,
double-blind, placebo-controlled phase 3 trial. Lancet 384: 403.
7.
Amano
M, Ishikawa H (2015) Pharmacological properties and
clinical efficacy of daclatasvir (Daklinza(®)) and asunaprevir (Sunvepra(®)).
Nihon Yakurigaku Zasshi 145: 152-162.
8.
Keating
GM (2015) Ledipasvir/Sofosbuvir: A review of its use in chronic hepatitis C.
Drugs 75: 675.
9.
Andreone
P, Colombo MG, Enejosa JV, Koksal I, Ferenci P, et al. (2014) ABT-450,
ritonavir, ombitasvir and dasabuvir achieves 97% and 100% sustained virologic
response with or without ribavirin in treatment-experienced patients with HCV
genotype 1b infection. Gastroenterology 147: 359.
10.
Zeuzem
S, Ghalib R, Reddy KR, Pockros PJ, Ari ZB, et al. (2015) Grazoprevir-Elbasvir combination
therapy for treatment-naive cirrhotic and non-cirrhotic patients with chronic
hepatitis C virus genotype 1, 4 or 6 infection: A randomized trial. Ann Intern
Med 163: 1-13.
11.
Hassanein
T, Sims KD, Bennett M, Gitlin N, Lawitz E, et al. (2015) A
randomized trial of daclatasvir in combination with asunaprevir and beclabuvir
in patients with chronic hepatitis C virus genotype 4 infection.
J Hepatol 62: 1204.
12.
Gerstoft
J (2016) Elbasvir/grazoprevir (Zepatier) for hepatitis C. Med Lett Drugs Ther
58: 25.
13.
Liu
JB, Pan XF (2016) Minimizing Kirchhoff index among graphs with a given vertex
bipartiteness, Elsevier Science Inc.
14.
Kang
MG, Kang MJ, Ji E, Yoo BK (2017) Meta-analysis of the efficacy and safety of
grazoprevir and elbasvir for the treatment of hepatitis C virus infection.
Korean J Clin Pharm 27: 150-160.