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Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease
worldwide [1]. The long-term impact of HCV infection is highly variable, ranging
from minimal histological changes to extensive brosis and cirrhosis with or without
hepatocellular carcinoma (HCC). The number of chronically infected persons
worldwide is estimated to be about 160 million, but most are unaware of their
infection. The implementation of extended criteria for screening for HCV is a subject
of major debate among different stakeholders. Clinical care for patients with HCVrelated liver disease has advanced considerably during the lasttwo decades,
thanksto an enhancedunderstanding of the pathophysiology of the disease, and
because of developments in diagnostic procedures and improvements in therapy
and prevention. These EASLRecommendations on Treatmentof HepatitisC are
intended to assist physicians and other healthcare providers, as well as patients and
other interested individuals, in the clinical decision-making process by describing
the current optimal managementofpatientswithacuteandchronicHCVinfections.These
recommendations apply to therapies that have been approved in the European
Union at the time of their publication.
----------------------------------------------------------------------------------------------------------------------------------------Hepatitis (inflammation of the liver) refers to a group of viral infections that affect
the liver. The most common types are hepatitis A, hepatitis B and hepatitis C. Each
is caused by a different virus.
Transformative advances in drug treatments approved by the Food and Drug
Administration are giving the 3.2 million Americans with chronic hepatitis C a
chance for a longer, healthier life without the virus. Thats welcome news for baby
boomerswho make up three of four adults with the hepatitis C virusand millions
of other Americans, many of whom dont yet know they are infected and carriers.
Hepatitis C is the most common chronic blood-borne infection in the United States.
There is no vaccine for this disease, but hepatitis C can be prevented by avoiding
behaviors that can spread the virusincluding sharing needles, syringes or other
equipment to inject drugs. A diagnosis of hepatitis C no longer means months and
months of painful drug injections, which for decades were the only option. Science
is making strides in therapies, giving patients new alternatives.
Hepatitis C is a deadly yet often overlooked disease that silently damages the liver over time. It is rarely
even treated, due to its nature of showing no symptoms as well as the mostly out-of-pocket cost of
treatment. Currently, less than 100 hepatitis C patients are undergoing treatment in the Philippines.
But in spite of all these barriers, there is now renewed hope for a cure.
Apart from the standard treatment composed of a combination therapy of peg-interferon (pegylated
interferon) and ribavirin, there is now a new addition to the treatment regimen that is poised to increase a
patients chance for virus eradication significantly, said Dr. Stuart Gordon, Director of the Division of
Hepatology and Hepatology Research at the Henry Ford Health System in Michigan and Professor of
Medicine at Wayne State University School of Medicine, Michigan.
Hepatitis C affects 3.2 million Americans and kills more people each year than
HIV/AIDS in the United States.
Approximately 3.2 million Americans are currently living with chronic hepatitis C, an
infection caused by the hepatitis C virus.1 Hepatitis C slowly destroys the liver over
time and can lead to serious and potentially life-threatening complications,
including liver cancer and the need for liver transplants.2 In addition to serious liver
damage, the complications of untreated hepatitis C can include Type 2 diabetes,
rheumatologic disorders and thyroid disease.3,4,5 Since the discovery of the virus in
1989, effectively treating hepatitis C has been a challenge. For years, the only
available treatment options were ineffective for many patients and often difficult to
tolerate.6 Initial treatment regimens involved up to a year of weekly interferon
injections and ribavirin tablets, which can cause side effects such as depression,
nausea, severe reductions in certain blood cells and flu-like symptoms.7 These often
difficult-to-tolerate treatment regimens, combined with low cure rates, caused many
patients to stop treatment before it was completed.
(daclatasvir), Olysio (simeprevir), Sovaldi (sofosbuvir), Technivie and Viekira Pak. Sovaldi and Olysio may
be prescribed together with or without ribavirin, or each may be separately combined with ribavirin and in
some cases peginterferon as well. Harvoni is two drugs formulated in to one daily pill, whereas Technivie
and Viekira Pak are a combination of medications that may be prescribed with or without ribavirin.
When hepatitis C treatment is working, the virus usually becomes undetectable within four to 12 weeks
and remains that way throughout treatment. People are considered cured when they have achieved what
is known as a sustained virologic response (SVR), or continuation of this undetectable status, 12 to 24
weeks after completing therapy.
BODY
What Medical Treatments Are Available?
If you are diagnosed with chronic hepatitis C, your doctor may recommend taking a
combination of medicines to try to prevent the virus from harming your liver. These
antiviral medicines are called interferon and ribavirin. Treatment with this combo usually
lasts between 24 and 48 weeks.
Since these drugs can lead to serious side effects, its important to discuss your
treatment options with your doctor. Not everyone who has chronic hepatitis C will
benefit from taking medicines.
For most people, hepatitis is a silent disease until it causes substantial damage to
the liver. That process may take several years, and can lead to liver failure, liver
transplantation and liver cancer. Hepatitis C is a bit like smoking, the longer youve
had it, the higher your risk of developing complicationsin this case, liver cancer
and end-stage liver disease. Its a progressive disease that takes years, even
decades, before the patient develops cirrhosis or cancer, Murray says. The good
news is that when you cure hepatitis C, you also lower its risks, though you dont
completely erase the years of damage to your liver.
Hepatitis C is an infectious disease affecting primarily the liver, caused by the hepatitis C
virus (HCV).[1] The infection is oftenasymptomatic, but chronic infection can lead to scarring of the
liver and ultimately to cirrhosis, which is generally apparent after many years. In some cases, those
with cirrhosis will go on to develop liver failure, liver cancer, or lifethreatening esophageal and gastric varices.[1]
HCV is spread primarily by blood-to-blood contact associated with intravenous drug use, poorly
sterilized medical equipment, andtransfusions. An estimated 150200 million people worldwide are
infected with hepatitis C.[2][3][4] The existence of hepatitis C originally identifiable only as a type of
non-A non-B hepatitis was suggested in the 1970s and proven in 1989. [5] Hepatitis C infects only
humans and chimpanzees.[6] It is one of five known hepatitis viruses: A, B, C, D, and E.
The virus persists in the liver in about 85% of those infected. This chronic infection can be treated
with medication: the standard therapy is a combination of peginterferon and ribavirin, with
either boceprevir or telaprevir added in some cases. Globally, an estimated 5095% of people
treated are cured.[7][8] With more recently developed medications cure rates are around 80 to 95%.
[8]
Those who develop cirrhosis or liver cancer may require a liver transplant. Hepatitis C is the leading
reason for liver transplantation, though the virus usually recurs after transplantation.
[9]
No vaccine against hepatitis C is available. About 343,000 deaths due to liver cancer from hepatitis
C occurred in 2013, up from 198,000 in 1990.[10] An additional 358,000 in 2013 occurred due to
cirrhosis.[10]
Both pegylated interferon alpha 2b and 2a; are given as a subcutaneous injection once a week.
Optimally, pegylated interferon therapy should be combined with oral ribavirin. In persons who
cannot take ribavirin, monotherapy with pegylated interferon may be used; however, monotherapy
has been shown to achieve sustained virologic response rates of only25%. Older preparations
(nonpegylated forms) of interferon are even less effective than pegylated interferon.
Ribavirin: The antiviral agent, ribavirin (Rebetol, Copegus), is a nucleoside analogue that is taken
by mouth. Nucleoside analogues are man-made molecules that closely resemble the biochemical
units that make up genetic material (RNA and DNA). Ribavirin works by fooling the virus into using it
instead of the normal building blocks of RNA, thereby slowing viral reproduction. Ribavirin has not
worked well when used alone for hepatitis C.
Combined pegylated interferon and ribavirin: Combined therapy with both pegylated interferon
and ribavirin produces a sustained virologic response or cure in 28% to 50% of patients with
genotype 1. (Genotype 1 is the most common genotype in the U.S., but also the most resistant to
treatment.) For unknown reasons, response rates are lower in African American persons and higher
in Caucasians. In patients with genotype 2, sustained response rates are higher (76% to 82%).
Duration of therapy depends on the genotype. Recommended duration of treatment for Genotype 1
is 48 weeks and for genotype 2 and 3 is 24 weeks.
Combination therapy is associated with more side effects than therapy with pegylated interferon
alone. (See below.) In research studies, up to 20% of patients receiving combination therapy
required a reduction in the doses or discontinuation of therapy because of the side effects.
Nevertheless, combination therapy represented significant progress in the treatment of chronic
hepatitis C.
Some patients treated successfully with combination therapy still have detectable virus after 24
weeks of treatment. Few of these patients go on to have a sustained response. Therefore, patients
on combination therapy should have hepatitis C virus RNA measured at 24 weeks of therapy. In
those who are still positive for the virus at that time, consideration is given to stopping treatment,
since the chance of a sustained response with further treatment is small.
medications- interferon, ribavirin and a new agent). The response to triple therapy was better than
with pegylated interferon and ribavirin, reaching approximately 80%. Telaprevir(Incivek) was
withdrawn from the market in 2014 by the manufacturer due to the availability of better drugs.
Sofosbuvir (Sovaldi) and simeprevir (Olysio) are oral therapeutic drugs, which were approved by
the FDA in 2013. These drugs can be used in combination with ribavirin and interferon, but
with simeprevir it is possible to eliminate the interferon. The effectiveness of treatment with these
combinations of medications is extremely high (greater than 90%), and it now provides an all oral
treatment.
Some of these new medications are also are known as direct acting antivirals (DAA) because they:
Directly attack and help kill the hepatitis C virus in the body
Ledipasvir and sofosbuvir (Harvoni) is a combination that is taken as one pill once a day is the
latest addition to the list of direct acting antivirals approved in 2014. With this therapy, the
effectiveness is even greater with a rate of sustained responses of 94%-99% with fewer side effects.
Duration of therapy also is reduced to 12 weeks (instead of the traditional 48 weeks with interferon
and ribavirin).
Ombitasvir, paritaprevir and ritonavir co-packaged with dasabuvir tablets (Viekira Pak), another
combination of oral direct acting antivirals was approved by the FDA in December 2014. The
sustained response rate of this combination was 91%-100%. As these medications are very new,
data is still limited, and more data is expected to be available in the near future.
Many other medications are under investigation but are not approved yet. The latest treatment
guidelines by American Association for the Study of Liver Disease (AASLD) and Infectious Disease
Society of America (IDSA) recommends use of these newer medications (direct acting antivirals) as
the primary treatment for hepatitis C infection and no longer recommend treatment with pegylated
interferon and ribavirin. The choice of direct acting antiviral varies by specific virus genotype and the
presence or absence of cirrhosis. In the U.S., specific insurance providers also might influence the
choice due to the high cost of direct acting antivirals. Patients are encouraged to discuss these
options with their physician on an individual basis.
relapse,
partial response
no response
Rapid viral response: Rapid viral response is defined as the absence of detectable HCV RNA in
serum using a sensitive test 4 weeks after initial treatment. Favorable response this early predicts
longer term treatment success.
End of treatment response: End of treatment response is defined as absence of HCV RNA in
blood using a sensitive test at the end of treatment, whatever duration of treatment has been
chosen.
Sustained virologic response: The optimal response is a sustained virologic response (SVR),
defined as the absence of detectable HCV RNA in serum using a sensitive test at the end of the
treatment and six months later. Most of these individuals will remain in remission (no signs of the
disease, cure) indefinitely, with no detectable hepatitis C virus RNA in the blood or liver. Moreover,
follow-up biopsies show a marked reduction in inflammation and there even can be regression of
scarring. Longer follow-up of these patients is necessary, however, to evaluate definitively whether
sustained responders will avoid the complications of cirrhosis and live longer.
Relapsers: Relapsers are patients who initially eliminate the RNA from their blood, but then develop
detectable RNA again shortly after discontinuing therapy. The RNA becomes detectable again within
six months and usually within the first three months of stopping treatment.
Partial responders: Patients whose HCV RNA levels decline (two log decrease), but never become
undetectable at 24 weeks are referred to as partial responders.
No response: Patients who have sustained levels of detectable HCV RNA during therapy are known
as non-responders. Patients in whom HCV RNA becomes undetectable during the early period of
treatment, but reappears before the end of therapy should probably likewise be considered nonresponders. This reappearance of HCV RNA during therapy is referred to as a 'break through' of
HCV.
Treating hepatitis C
stopping smoking
keeping personal items, such as toothbrushes or razors, for your own
use
not sharing any needles or syringes with others
Read some FAQs about living with hepatitis C for more information.
Hepatitis C medications
Currently, treatment for chronic hepatitis C usually involves taking two main
medicines:
pegylated interferon a medication that encourages the immune
system to attack the virus
ribavirin an antiviral medication that stops the virus reproducing
These medications may just be taken together, although they're often
combined with a third medication, such as simeprevir or sofosbuvir.
These are newer hepatitis C medications that have been shown to make
treatment more effective. Read more about all these medications below.
Pegylated interferon and ribavirin
Pegylated interferon is usually taken as a weekly injection. You can be trained
to inject yourself at home. It usually needs to be taken for up to 48 weeks,
depending on your circumstances.
Ribavirin is available as capsules, tablets or an oral solution. It's normally
taken twice a day with food. It needs to be taken alongside pegylated
interferon for up to 48 weeks.
For more information see the National Institute for Health and Care
Excellence (NICE) guidelines on peginterferon alfa and ribavirin for the
treatment of chronic hepatitis C.
Simeprevir and sofosbuvir
Medications
Treatment with antiviral medication is recommended in all people with proven chronic hepatitis C
who are not at high risk of dying from other causes.[74] People with the highest complication risk
should be treated first, with the risk of complications based on the degree of liver scarring. [74] The
initial recommended treatment depends on the type of hepatitis C virus with which a person is
infected.[74]
Sofosbuvir with ribavirin and interferon appears to be around 90% effective in those with genotype 1,
4, 5, or 6 disease.[75] Sofosbuvir with just ribavirin appears to be 70 to 95% effective in type 2 and 3
disease but has a higher rate of adverse effects.[76][75] Treatments that contain ledipasvir and
sofosbuvir for genotype 1 has success rates of around 93 to 99% but is very expensive. [77] In
genotype 6 infection, pegylated interferon and ribavirin is effective in 60 to 90% of cases. [7] There is
some tentative data for simeprevir use in type 6 disease as well.[7]
Prior to 2011, treatments consisted of a combination of pegylated interferon alpha and ribavirin for a
period of 24 or 48 weeks, depending on HCV genotype.[12] This produces cure rates of between 70
and 80% for genotype 2 and 3, respectively, and 45 to 70% for genotypes 1 and 4. [76] Adverse effects
with these treatments were common, with half of people getting flu like symptoms and a third
experiencing emotional problems.[12] Treatment during the first six months is more effective than
once hepatitis C has become chronic.[25]
Surgery
Cirrhosis due to hepatitis C is a common reason for liver transplantation[25] though the virus usually
(8090% of cases) recurs afterwards.[9][78] Infection of the graft leads to 1030% of people developing
cirrhosis within five years.[79] Treatment with pegylated interferon and ribavirin post transplant
decreases the risk of recurrence to 70%.[80]
Alternative medicine
Several alternative therapies are claimed by their proponents to be helpful for hepatitis
C including milk thistle, ginseng, and colloidal silver.[81] However, no alternative therapy has been
shown to improve outcomes in hepatitis C, and no evidence exists that alternative therapies have
any effect on the virus at all.[
in patients with advanced liver disease (brosis METAVIR score F3 or F4). The
combination of sofosbuvir and ribavirin is indicated in patients infected with
HCV.
AbbVie's VIEKIRAX Approved In Japan For Genotype 1 Chronic Hepatitis C
ABBVIE'S VIEKIRAX (OMBITASVIR/PARITAPREVIR/RITONAVIR TABLETS)
RECEIVES APPROVAL IN JAPAN FOR THE TREATMENT OF GENOTYPE 1 CHRONIC
HEPATITIS C
- NEW INTERFERON AND RIBAVIRIN-FREE TREATMENT OPTION FOR PATIENTS WITH
MOST COMMON TYPE OF HEPATITIS IN JAPAN, GENOTYPE 1 CHRONIC HEPATITIS C,
INCLUDING THOSE WITH COMPENSATED CIRRHOSIS[1]
- VIEKIRAX CONSISTS OF A 12-WEEK, TWO DIRECT-ACTING ANTIVIRAL, FIXED-DOSE
COMBINATION OF PARITAPREVIR/RITONAVIR WITH OMBITASVIR, DOSED ONCE
DAILY[1]
- APPROXIMATELY 1.5 TO 2 MILLION PEOPLE ARE LIVING WITH HEPATITIS C IN JAPAN,
ONE OF THE HIGHEST RATES OF HEPATITIS C INFECTION IN THE INDUSTRIALIZED
WORLD[2],[3]
Sep 28, 2015
NORTH CHICAGO, Ill., Sept. 28, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global
biopharmaceutical company, today announced that the Japanese Ministry of Health,
Labour and Welfare (MHLW) approved VIEKIRAX(ombitasvir/paritaprevir/ritonavir),
as a new interferon and ribavirin-free treatment option for adult patients with
chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with
compensated liver cirrhosis.1 VIEKIRAX consists of a 12-week, two direct-acting
antiviral, xed-dose combination of paritaprevir/ritonavir with ombitasvir, dosed
once daily.
"Today's approval represents an important step forward for the treatment of
Japanese patients, a population with specic needs based on patient and viral
characteristics," said Jean-Michel Pawlotsky, MD, PhD, professor of medicine at the
University of Paris-Est, France. "VIEKIRAX is a valuable new addition to a number of
treatments that are changing the face of hepatitis C, making it possible to achieve
high virologic cure rates, even in patients whose disease has progressed to
compensated liver cirrhosis."
Japan has one of the highest rates of hepatitis C infection in the industrialized world,
with approximately 1.5 to 2 million people living with HCV.2, 3 Genotype 1 is the
cirrhotic GT1b patients who were eligible for therapy with IFN and had a high viral
load, dened as an HCV RNA level 100,000 IU/mL and received at least one dose
of the double-blind, active study drug.
In sub-study 2, 42 GT1b treatment-nave and IFN (with or without RBV) treatmentexperienced patients with compensated cirrhosis received open-label treatment for
12 weeks (Arm C) with SVR12 and assessed as a secondary efficacy endpoint.
One patient from each arm (n=3/363) experienced on-treatment virologic failure
[Arm A, 0.5% (n=1/215); Arm B, 0.9% (n=1/106); Arm C, 2.4% (n=1/42)]. Across all
arms, eight patients (n=8/354) experienced post-treatment relapse [Arm A, 2.4%
(n=5/209); Arm B, 1.0% (n=1/105); Arm C, 5.0% (n=2/40)].
AbbVie studied its two direct-acting antiviral treatment regimen without RBV in
Japan due to patient and viral characteristics specic to the Japanese population,
including high prevalence of GT1b.
hepatitis C," said Norbert Bischofberger, PhD, Executive Vice President of Research
and Development and Chief Scientic Officer at Gilead. "Genotype 1 is the most
prevalent form of HCV in the United States, but worldwide, more than half of people
living with HCV are infected with other genotypes. SOF/VEL complements our
current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the
potential to simplify treatment and eliminate the need for HCV genotype testing."
The FDA has assigned SOF/VEL a Breakthrough Therapy designation, which is
granted to investigational medicines that may offer major advances in treatment
over existing options. The NDA for SOF/VEL is supported by data from four Phase 3
ASTRAL trials, which evaluated the xed-dose combination in hepatitis C genotypes
1-6. Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1,
ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy
endpoint of SVR12. The ASTRAL-4 study randomized 267 patients with
decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with
or without ribavirin (RBV), or 24 weeks of SOF/VEL. Those who received SOF/VEL
plus RBV for 12 weeks achieved an SVR12 rate of 94 percent, while those who
received SOF/VEL for 12 weeks and 24 weeks achieved SVR12 rates of 83 percent
and 86 percent, respectively.
Patients treated with SOF/VEL for 12 weeks in ASTRAL-1, ASTRAL-2 and ASTRAL-3
had similar adverse events compared with placebo-treated patients in ASTRAL-1.
The most common adverse events were headache, fatigue and nausea. The most
common adverse events in ASTRAL-4 were fatigue, nausea and headache.
Gilead plans to submit a regulatory application for approval of SOF/VEL in the
European Union by the end of the year.
The SOF/VEL xed-dose combination is an investigational product and its safety and
efficacy have not been established.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and
commercializes innovative therapeutics in areas of unmet medical need. The
company's mission is to advance the care of patients suffering from life-threatening
diseases. Gilead has operations in more than 30 countries worldwide, with
headquarters in Foster City, California.
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995 that are subject to risks,
uncertainties and other factors, including the risk that FDA may not approve the
SOF/VEL xed-dose combination, and that any marketing approvals, if granted, may
have signicant limitations on its use. In addition, Gilead may be unable to le for
regulatory approval of SOF/VEL in other geographies in the currently anticipated
timelines. Further, additional clinical studies of SOF/VEL may produce unfavorable
results. As a result, Gilead may not be able to successfully commercialize SOF/VEL.
These risks, uncertainties and other factors could cause actual results to differ
materially from those referred to in the forward-looking statements. The reader is
cautioned not to rely on these forward-looking statements. These and other risks
are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter
ended June 30, 2015, as led with the U.S. Securities and Exchange Commission. All
forward-looking statements are based on information currently available to Gilead,
and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Sovaldi and Harvoni is available
atwww.gilead.com.
Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc. or its related
companies.
CONCLUSION
What are the goals of therapy for hepatitis C infection?
The ultimate goals of antiviral therapy are to:
eliminate hepatitis C,
As previously mentioned, only a sustained virologic response provides the possibility of achieving all
of these goals since most patients who have a sustained response will remain in remission
indefinitely. The rest of the patients (non-responders, partial responders, and relapsers) may show
improvement in blood tests with or without relief of symptoms.
What is the current research and what is in the future for hepatitis C?
As our knowledge of hepatitis C increases, more and more patients are being diagnosed with
chronic infection. Current research includes diagnosis, natural history, treatment, and vaccine
development.
Diagnosis: More accurate tests are being developed to detect even smaller amounts of the
virus.
Natural history: There is much we do not know about the natural history of chronic hepatitis
C. Why do some people clear the virus spontaneously? What makes some people develop
cirrhosis when others appear to have little liver damage? What predicts response to treatment
or re-treatment?
Treatment: New medications are being developed in the hopes of improving response rates
even further. In addition, newer oral medications not requiring interferon are in early stages of
testing that have SVRs upwards of 95%.
Vaccine development: Scientists have not been able to develop an effective vaccine
against hepatitis C. This is partly due to the ability of hepatitis C to change (mutate) and evade
the body's immune responses. Attempts to develop a vaccine, however, are continuing.
Unlike other serious chronic diseases, hepatitis C has the ability to be cured
When it comes to hepatitis C, the outlook for the future is better, but the past is
catching up with us especially if you are a baby boomer, Murray says. Still, this
is a fortuitous time because better hepatitis C treatments are becoming available
just as the patient population at risk of long-term complications is about to peak.
There are treatments for chronic hepatitis and many reasons to get tested now
more than ever because of the availability of safe and effective therapies.
WHEN AND IN WHOM TO INITIATE HCV THERAPY
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Successful hepatitis C treatment results in sustained virologic response (SVR), which
is tantamount to virologic cure, and as such, is expected to benet nearly all
chronically infected persons. When the US Food and Drug Administration (FDA)
approved the rst IFN-sparing treatment for HCV infection, many patients who had
previously been warehoused sought treatment, and the infrastructure
(experienced practitioners, budgeted health-care dollars, etc) did not yet exist to
treat all patients immediately. Thus, the panel offered guidance for prioritizing
treatment rst to those with the greatest need. Since that time, there have been
opportunities to treat many of the highest-risk patients and to accumulate realworld experience of the tolerability and safety of newer HCV medications. More
importantly, from a medical standpoint, data continue to accumulate that
demonstrate the many benets, within the liver and extrahepatic, that accompany
HCV eradication. Therefore, the panel continues to recommend treatment for all
patients with chronic HCV infection, except those with short life expectancies that
cannot be remediated by treating HCV, by transplantation, or by other directed
therapy. Accordingly, prioritization tables are now less useful and have been
removed from this section.
Despite the strong recommendation for treatment for nearly all HCV-infected
patients, pretreatment assessment of a patients understanding of treatment goals
and provision of education on adherence and follow-up are essential. A wellestablished therapeutic relationship between practitioner and patient remains
crucial for optimal outcomes with new direct-acting antiviral (DAA) therapies.
Additionally, in certain settings there remain factors that impact access to
medications and the ability to deliver them to patients. In these settings,
practitioners may still need to decide which patients should be treated rst. The
descriptions below of unique populations may help physicians make more informed
treatment decisions for these groups.
Clinical Benefit of Cure
The proximate goal of HCV therapy is SVR (virologic cure), defined as the continued absence of detectable HCV
RNA at least 12 weeks after completion of therapy. SVR is a marker for cure of HCV infection and has been shown to
be durable, in large prospective studies, in more than 99% of patients followed up for 5 years or more. (Swain,
2010); (Manns, 2013) Patients in whom an SVR is achieved have HCV antibodies but no longer have detectable
HCV RNA in serum, liver tissue, or mononuclear cells, and achieve substantial improvement in liver histology.
(Marcellin, 1997); (Coppola, 2013); (Garcia-Bengoechea, 1999) Assessment of viral response, including
documentation of SVR, requires use of an FDA-approved quantitative or qualitative nucleic acid test (NAT) with a
detection level of 25 IU/mL or lower.
Patients who are cured of their HCV infection experience numerous health benefits, including a decrease in liver
inflammation as reflected by improved aminotransferase (ie, alanine aminotransferase [ALT], aspartate
aminotransferase [AST]) levels and a reduction in the rate of progression of liver fibrosis. (Poynard, 2002b) Of 3010
treatment-naive HCV-infected patients with pretreatment and posttreatment biopsies from 4 randomized trials of 10
different IFN-based regimens (biopsies separated by a mean of 20 months), 39% to 73% of patients who achieved an
SVR had improvement in liver fibrosis and necrosis (Poynard, 2002b), and cirrhosis resolved in half of the cases.
Portal hypertension, splenomegaly, and other clinical manifestations of advanced liver disease also improved. Among
HCV-infected persons, SVR is associated with a more than 70% reduction in the risk of liver cancer (hepatocellular
carcinoma [HCC]) and a 90% reduction in the risk of liver-related mortality and liver transplantation. (Morgan, 2013);
(van der Meer, 2012); (Veldt, 2007)
Cure of HCV infection also reduces symptoms and mortality from severe extrahepatic manifestations, including
cryoglobulinemic vasculitis, a condition affecting 10% to 15% of HCV-infected patients. (Fabrizi, 2013); (Landau,
2010) HCV-infected persons with non-Hodgkin lymphoma and other lymphoproliferative disorders achieve complete
or partial remission in up to 75% of cases following successful therapy for HCV infection. (Gisbert, 2005);
(Takahashi, 2012); (Svoboda, 2005); (Mazzaro, 2002); (Hermine, 2002) These reductions in disease severity
contribute to dramatic reductions in all-cause mortality. (van der Meer, 2012); (Backus, 2011) Lastly, patients who
achieve SVR have substantially improved qualities of life, which include physical, emotional, and social health.
(Neary, 1999); (Younossi, 2013) Because of the many benefits associated with successful HCV treatment,
clinicians should treat HCV-infected patients with antiviral therapy with the goal of achieving an SVR, preferably early
in the course of chronic HCV infection before the development of severe liver disease and other complications.
REFERENCE
Faster, Easier Cures for Hepatitis. FDA Consumer Health Information / U.S. Food and
Drug Administration. July 2014
Innovating and Expanding Access to Hepatitis C Treatments. Gilead Sciences Policy
Position. October 2014
1.
Ryan KJ, Ray CG (editors), ed. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 551
2. ISBN 0838585299.
2. ^ Jump up to:a b Gravitz L. (2011). "A smouldering public-health crisis". Nature 474 (7350): S2
4.doi:10.1038/474S2a. PMID 21666731.
3. ^ Jump up to:a b c d "Hepatitis C". World Health Organization (WHO). June 2011. Retrieved2011-07-13.
4. ^ Jump up to:a b c Mohd Hanafiah, K; Groeger, J; Flaxman, AD; Wiersma, ST (April 2013). "Global
epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV
seroprevalence.". Hepatology (Baltimore, Md.) 57 (4): 1333
42. doi:10.1002/hep.26141.PMID 23172780.
5. Jump up^ Houghton M (November 2009). "The long and winding road leading to the identification of
the hepatitis C virus". Journal of Hepatology 51 (5): 939
48.doi:10.1016/j.jhep.2009.08.004. PMID 19781804.
6. Jump up^ Shors, Teri (2011-11-08). Understanding viruses (2nd ed.). Burlington, MA: Jones & Bartlett
Learning. p. 535. ISBN 9780763785536.
7. ^ Jump up to:a b c Bunchorntavakul, C; Chavalitdhamrong, D; Tanwandee, T (Sep 27, 2013). "Hepatitis
C genotype 6: A concise review and response-guided therapy proposal.". World journal of
hepatology 5 (9): 496504. doi:10.4254/wjh.v5.i9.496. PMID 24073301.
8. ^ Jump up to:a b "Hepatitis C FAQs for Health Professionals". CDC. October 14, 2015. Retrieved31
October 2015. Clinical trials have shown that these new medications achieve SVR in 80%-95% of
patients after 12-24 weeks of treatment.
20. ^ Jump up to:a b Hepatitis C and CAM: What the Science Says. National Center for Complementary
and Alternative Medicine (NCCAM). March 2011. (Retrieved 7 March 2011)
21. Jump up^ Liu, J; Manheimer E; Tsutani K; Gluud C (March 2003). "Medicinal herbs for hepatitis C
virus infection: a Cochrane hepatobiliary systematic review of randomized trials". The American journal
of gastroenterology 98 (3): 53844. doi:10.1111/j.1572-0241.2003.07298.x. PMID 12650784.
22. Jump up^ Rambaldi, A; Jacobs, BP; Gluud, C (17 October 2007). "Milk thistle for alcoholic and/or
hepatitis B or C virus liver diseases.". The Cochrane database of systematic reviews (4):
CD003620. doi:10.1002/14651858.CD003620.pub3. PMID 17943794.