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Moghe et al. Hepatoma Res 2018;4:36 I http://dx.doi.org/10.20517/2394-5079.2018.54 Page 3 of 9

Table 1. Timeline of drug approvals for hepatitis C (USA)
Approval date Anti-viral agent Trade name
Feb 26, 1991 Interferon alfa-2b Intron-A
1996 Interferon alfa-2a Roferon
Sep 10, 1997 Interferon alfacon-1 Infergen
Aug 7, 2001 Peginterferon alfa-2b Peg-Intron
Oct 16, 2002 Peginterferon alfa-2a Pegasys
May 13, 2011 Boceprevir Victrelis
May 23, 2011 Telaprevir Incivek
Nov 24, 2013 Simeprevir Olysio
Dec 6, 2013 Sofosbuvir Sovaldi
Oct 10, 2014 Sofosbuvir/ledipasvir Harvoni
Dec 19, 2014 Ombitasvir/paritaprevir/ritonavir/dasabuvir Viekira Pak
Jul 24, 2015 Daclatasvir Daklinza
Jul 24, 2015 Ombitasvir/paritaprevir/ritonavir Technivie
Jan 28, 2016 Elbasvir/grazoprevir Zepatier
Jun 28, 2016 Sofosbuvir/velpatasvir Epclusa
Jul 18, 2017 Sofosbuvir/velpatasvir/voxilaprevir Vosevi
Aug 3, 2017 Glecaprevir/pibrentasvir Mavyret

Developed countries have typically demonstrated lower prevalence of HCV infection compared to
developing countries. In the United States, HCV seroprevalence is 1.6% to 1.8%, amounting to 5-7 million
individuals [15,18] . The populations at risk are intravenous drug users, incarcerated and homeless persons,
and those born in the “baby boomer” years between 1945 and 1965. During those years, extensive illicit
intravenous drug use in social settings and the use of contaminated blood products led to the spread of
HCV. Since the establishment of standard screening practices for blood products and organs, a noticeable
decline of incident HCV cases has been noted [18-20] . This is also true for other developed countries including
Australia, Japan and parts of Europe . Currently, the major risk factor for transmission in those countries
[15]
[15]
is the sharing of infected needles by intravenous drug users .
As HCV and HIV have similar routes of transmission, co-infection is common especially in countries such
as Thailand, Malaysia and China, where intravenous drug abuse and addiction are major problems . Of the
[21]
40 million known HIV infected persons in the world, approximately 4.5 million are co-infected with HCV .
[22]
Unfortunately, HIV-induced immunosuppression leads to accelerated progression of HCV disease, resulting
in cirrhosis within 5-10 years of infection rather than the usual 10-20 years . Alcohol abuse also accelerates
[21]
HCV disease progression.

HCV TREATMENT - EVOLUTION FROM INTERFERONS TO DIRECT-ACTING ANTIVIRALS
Before the turn of the century, standard treatment for chronic hepatitis C consisted of the combination of
interferon-alfa administered three times a week with ribavirin daily for 24 or 48 weeks [23,24] . Subsequent
introduction of pegylated interferons allowed for once a week injections and improved response rates. Still,
treatment was associated with considerable side-effects limiting its applicability particularly among patients
with comorbidities and organ transplant status other than liver transplantation.

The introduction of direct-acting antivirals (DAA), telaprevir and boceprevir, in 2011 dawned a new era in
the management of HCV infection [Table 1]. Both drugs were NS3/4A protease inhibitors, and were used in
[25]
combination with peg-interferons and ribavirin to avoid the emergence of resistant variants . Those agents
[26]
improved SVR rates but did not improve the side-effect profile. Thus, the use of triple therapy came with its
own challenges particularly with regard to compliance and monitoring . Simeprevir was another protease
[15]
inhibitor that was approved to be used in combination with peginterferon and ribavirin with similar effects.
Those three drugs constituted the first generation of DAAs.