US Pharm. 2014;39(4):18-20.
In the United States, an estimated 3.2
million people are living with chronic hepatitis C virus (HCV)
infection, the potentially fatal liver disease.1 While anyone can get HCV, more than 75% of these are baby boomers—the generation born between 1945 and 1965.2
In 75% to 85% of persons initially infected with HCV, the disease
becomes chronic; progression of liver fibrosis is more rapid in those
who acquire the infection at an older age.3,4
HCV is considered a silent killer, since the disease can progress for decades without any indications of illness.1,2 Though it is silent, its destructive capacity renders it a leading cause of liver disease and liver cancer.2,5
HCV is the leading cause of liver transplants in the U.S.; the virus
recurs almost universally following liver transplantation, resulting in
chronic hepatitis or cirrhosis in 90% of patients within 5 years.2,5,6
Deaths attributed to HCV were as high as 16,600 in 2010, according to the CDC; had these patients been diagnosed and treated earlier, many deaths could have been prevented.7 HCV prevalence varies with geography and other risk factors.8 The CDC recommends testing for HCV in high-risk individuals (
), which includes anyone born from 1945 to 1965, the age group that is five times more likely to have HCV.2 Currently, there is no vaccine (i.e., immunoprophylaxis) for HCV.1
Why Baby Boomers?
Health officials believe that most people
infected with HCV do not know it. Hence, an initiative has begun to
increase awareness (see
and to have healthcare providers request that those at risk get tested.
HCV is commonly thought to affect mostly IV drug users.7
According to the CDC, baby boomers are more likely to suffer from HCV
than others owing to the high rates of experimental drug use in the
1960s and 1970s, in addition to the lack of oversight provided to the
transfusion blood supply before 1992.7 Most of the elderly who have HCV infection have acquired it from blood transfusions.3
Baby boomers, who are currently in their late 40s to late 60s, may not be aware of their exposure to potentially infected blood.7
At present, transmission of HCV through blood transfusion has become
very rare since the advent of screening tests for donated blood. Of
note, however, some sporadic cases do occur in patients without apparent
risk factors.8 HCV may also be contracted when poor infection-control practices are used during tattooing or body piercing.4
While it is possible to contract the disease through sex, it is
uncommon; risk increases for those who have multiple sex partners, have a
sexually transmitted disease, engage in rough sex, or are infected with
outlines key characteristics of HCV with which pharmacists should be familiar.
Clinical Manifestations and Complications
Approximately 70% to 80% of people with acute HCV do not have any symptoms.4
Mild-to-severe symptoms that appear soon after being infected include
fever, fatigue, and loss of appetite; nausea, vomiting, and abdominal
pain; dark urine and clay-colored bowel movements; joint pain; and
jaundice.4 The severity of HCV infection often
fluctuates. Symptoms of hepatitis may recur after temporary abatement.
Furthermore, aminotransferase levels may roller-coaster for many years,
or even decades.8 While patients are usually asymptomatic
when HCV becomes chronic, the disease does progress to cirrhosis in 20%
to 30% of cases and often takes decades to manifest.8 In
patients with HCV-induced cirrhosis, hepatocellular carcinoma can ensue,
but this is only rarely the case in chronic HCV infection without
cirrhosis.8 Of note, up to 20% of patients with alcoholic
liver disease harbor HCV; alcohol and HCV act synergistically to worsen
liver inflammation and fibrosis.8
There has been limited efficacy associated with treatment of HCV (see Treatment
below); thus, prevention of viral hepatitis is very important.
Practicing good personal hygiene assists in the prevention of
transmission; blood (i.e., found on razors and toothbrushes) and other
body fluids (e.g., saliva, semen) of patients with acute HCV infection
are considered infectious.4,8 While barrier protection is recommended, isolating patients is of no value in HCV infection.8
Avoiding unnecessary transfusions and screening all blood donors for
HCV antibodies (anti-HCV) can minimize posttransfusion infection;
screening has been shown to decrease the incidence of posttransfusion
hepatitis.8 Currently, there is no product that exists for
immunoprophylaxis of HCV; in an infected individual, HCV is capable of
altering its amino acid pattern over time, producing quasispecies, which
hampers vaccine development.8
Treatment of HCV consists of supportive care and treatment of the cause.9 Successful treatment can eliminate the virus from the body and prevent liver damage, cirrhosis, and even liver cancer.2 Goals of treatment include treating the cause in addition to managing complications (e.g., ascites, encephalopathy).9
To that end, it is imperative to identify and discontinue any drugs
that cause hepatitis and to treat other underlying disorders, (e.g.
Wilson disease, characterized by cirrhosis of the liver).9 Agents that enhance viral replication (e.g., corticosteroids,
immunosuppressants) should be avoided in chronic HCV.9
For chronic HCV, the genotype (1, 2, 3,
4, 5, and 6) determines the course, duration, and success of therapy;
genotype 1 accounts for up to 80% of cases in the U.S.9 Patients
with all genotypes are traditionally treated with peginterferon
(PEG-IFN) alpha-2a or -2b plus weight-based ribavirin (RBV);
additionally, a direct-acting antiviral affecting specific HCV targets
such as proteases or polymerases is added for specific genotypes.9-12
The addition of an HCV protease inhibitor (telaprevir, boceprevir, or
simeprevir) to PEG-IFN and RBV represents an important advance in the
treatment of patients with genotype 1, increasing the rate of sustained
virologic response (permanent elimination of HCV-RNA)9, 13
The HCV polymerase inhibitor sofosbuvir is effective against HCV
genotypes 1–6 and can be used without interferon, creating an all-oral
regimen of sofosbuvir plus RBV for genotypes 2 and 3; this regimen may
also be useful for patients who have contraindications to or who are
refractory to treatment with interferon-based regimens.9,11 See RESOURCES for specific dosing regimens. Two recently published studies involving all-oral, IFN-free regimens are briefly discussed below.
In the first study, oral daclatasvir
(still in the approval process) 60 mg once daily and oral sofosbuvir 400
mg once daily for either 12 or 24 weeks were tested, with or without a
third drug, ribavirin.5,14 Sulkowski et al concluded that
once-daily oral daclatasvir plus sofosbuvir was associated with high
rates of sustained virologic response among patients infected with HCV
genotype 1, 2, or 3, including those with no response to prior therapy
with telaprevir or boceprevir.5,14 Pharmacists should note that this was an open-label study funded by Bristol-Myers Squibb and Pharmasset (Gilead).
In a second study, participants were
randomly assigned to take any of three combinations of antiviral
agents—medications called ABT-450, ABT-267, and ABT-333—for 8, 12, or 24
weeks. Kowdley et al concluded that in this phase 2b study, all-oral
regimens of antiviral agents and ribavirin were effective both in
patients with HCV genotype 1 infection who had not received therapy
previously and in those who had not had a response to prior therapy.15
Pharmacists should note that this was an open-label study funded by
AbbVie. Lok, a coauthor of the first study, remarked that while
pharmaceutical companies funded both studies, the companies carefully
scrutinized the data, and the data will be examined by the FDA as well.5 For further details of these data, see References 14 and 15.
Updated Information and Guidance: Treatment
for HCV infection has evolved significantly since the introduction of
highly effective HCV protease inhibitor therapies in 2011, and it is
expected to accelerate, for new agents with varied mechanisms of action
will probably become available over the next few years.16 The
American Association for the Study of Liver Diseases and the Infectious
Diseases Society of America have created a website designed for the
rapid formulation and dissemination of evidence-based recommendations
for HCV management; developed by experts, these recommendations provide
healthcare professionals with timely guidance as new therapies become
available and are integrated into HCV regimens, including those by HCV
genotype (see Reference 16). The associations’ guidance is presented as a
“living document” that will continually provide updated information and
direction on FDA-approved regimens; it may also recommend off-label use
of certain drugs or tests or provide information on regimens not yet
approved by the FDA.16 Additionally, data from cost-effectiveness studies may guide treatment choice in the future as well (see Cost Implications,
below). Pharmacists are encouraged to review the latest recommendations
on this website and look for the soon-to-be-posted “Monitoring Patients
Who Are On or Have Completed Therapy,” which will offer guidance to
those providing pharmaceutical care for patients with HCV. For a table
of approved treatments for HCV, see Reference 13; for special geriatric
considerations, see Reference 12.
Cost Implications: More
Americans now die from hepatitis C than from HIV, according to
1999-2007 data reviewed by the CDC; most of those dying are middle-aged.17
Lok indicated in an interview that cost is an issue regarding
interferon-free regimens and will therefore make these treatments
inaccessible to many patients.5,14 In light of initiatives
for additional screening, an increase in demand for treatment can
potentially place an enormous burden on Medicare and Medicaid agencies,
private insurers, and taxpayers. The implications of the recent FDA
approval of simeprevir and sofosbuvir are staggering given the high cost
of these agents and the huge number of people who could benefit from
treatment.17 Experts have indicated the possibility of drug
rationing and an impact on insurance premiums; further, a new generation
of HCV medications is expected to gain FDA approval later this year.17
Liver disease, liver cancer, and deaths
from HCV are on the rise, and no vaccine is available for contacts of
patients with this infection. Pharmacists can encourage the testing of
high-risk individuals, including those born between 1945 and 1965.
Furthermore, pharmacists can guide patients and healthcare providers
regarding available treatments that can eliminate HCV from infected
individuals and prevent liver damage, cirrhosis, and even liver cancer
associated with this disease.
1. Reinberg S. Baby boomers need hepatitis C Test, CDC study confirms. WebMD.
Aging Well. August 15, 2013.
Accessed February 19, 2014.
2. Centers for Disease Control and
Prevention. U.S. Department of Health and Human Services. Hepatitis C:
why baby boomers should get tested. May 2013.
February 19, 2014.
3. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet. 1997;349:825-832.
4. Centers for Disease Control and
Prevention. Hepatitis C FAQs for the public. Last reviewed February 10,
2014. www.cdc.gov/hepatitis/c/cfaq.htm#cFAQ22. Accessed March 19, 2014.
5. Marcus MB. Most with hepatitis C may soon find hope in new treatments. WebMD.
News from HealthDay.
Accessed February 19, 2014.
6. Johnson HJ, Schonder KS. Solid-organ transplantation. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill Inc; 2011:1555.
7. Walker J. Doctors push to screen baby boomers for hepatitis C. Health & Wellness. Wall Street Journal. Oct. 28, 2013. http://online.wsj.com/news/articles/SB10001424052702304200804579163523170170660. Accessed February 19, 2014.
8. Acute Viral Hepatitis. Hepatic and
biliary disorders. Merckmanuals.com. Last full review/revision February
2014. Accessed March 31. 2014.
9. Chronic hepatitis. Merckmanuals.com.
Last full review/revision March 2013.
c&alt=sh. Accessed February 19, 2014.
10. Clark MA, Finkel R, Rey JA., eds. Pharmacology. 5th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2012:461-466.
11. Epocrates Essentials Version 4.5. www.epocrates.com. Accessed March 10, 2014.
12. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 19th ed. Hudson, OH: Lexicomp; 2014.
13. U.S. Food and Drug Administration,
U.S. Department of Health and Human Services. Updated 12/07/2013.
Accessed March 19, 2014.
14. Sulkowski MS, Gardiner DF,
Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously
treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211-221.
15. Kowdley KV, Lawitz E, Poordad F, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014;370:222-232.
16. American Association for the Study of
Liver Diseases and the Infectious Diseases Society of America.
Recommendations for testing, managing, and treating hepatitis C.
www.hcvguidelines.org/. Accessed March 8, 2014.
17. Ollove M. Hep C. USA Today.
March 3, 2014.
Accessed March 10, 2014.
18. Hurley J, Green JT. The liver. In: Fillit HM, Rockwood K, Woodhouse K, eds. Brocklehurst’s Textbook of Geriatric Medicine and Gerontology. 7th ed. Philadelphia, PA: Saunders Elsevier; 2010:635-644.
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