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HEPATITIS C
INTRODUCTION
Hepatitis C is a virus that causes a chronic infection of the liver. The hepatitis C virus
was first identified in 1989. Since that time, hepatitis C has become a serious worldwide
health issue. It has been estimated that approximately 170 million people are infected
with hepatitis C. It is a significant cause of liver cancer, cirrhosis, and hepatitis, and as
the population ages, it is expected that the number of people affected and the burden on
the health care system will both increase. Improved screening techniques have
significantly decreased the chances of hepatitis C being transmitted during blood
transfusions. The majority of cases (in developed countries) are caused by IV drug use,
and this is obviously a social issue that is very difficult to manage. There is no vaccine
for hepatitis C, the available treatment is long, expensive, and risky, and the success rate
for the therapy varies considerably depending on the form of the virus and other factors.
OBJECTIVES
When the student has finished this module, she/he will be able to:
1. Identify the correct definition of hepatitis C.
2. Identify the 2 most important clinical implications of hepatitis C infection.
3. Identify the type of virus that hepatitis C is considered to be.
4. Identify 3 characteristics of the virus that have treatment implications.
5. Identify the major route of transmission of hepatitis C in developed countries.
6. Identify the percentage of people with hepatitis C infection who will develop cirrhosis.
7. Identify the percentage of people with hepatitis C infection who will develop liver
cancer.
8. Identify 3 relatively common complications of a hepatitis C infection.
9. Identify the 2 blood tests that are used to confirm the presence of hepatitis C.
10. Identify the “gold standard” test used to assess fibrosis and cirrhosis in patients with a
hepatitis C infection.
11. Identify 2 other tests that can be used to detect fibrosis and cirrhosis.
12. Identify the most common genotype of hepatitis C in the United States.
13. Identify 2 factors that increase the risk of developing liver cancer.
14. Identify 3 patient characteristics that would indicate the need to screen for hepatitis C.
15. Identify a drug used to treat hepatitis C and its mode of action.
16. Identify a drug used to treat hepatitis C and its mode of action.
17. Identify the factor that most determines the success rate of the therapy for hepatitis C.
18. Identify the correct definition of sustained viral response.
19. Identify a serious, commonly experienced adverse effect of the therapy for hepatitis
C.
20. Identify a commonly experienced psychological adverse effect of the therapy used to
treat hepatitis C.
EPIDEMIOLOGY
Hepatitis C is the most common chronic, blood-borne disease in the United States.1
The Centers for Disease Control (CDC) has estimated that approximately 1.8% of the
population of the United States has been exposed to hepatitis C, and of that number, 75%
are viremic.2 Those numbers would mean that there are 2.7 million people with an active
hepatitis C infection. Hepatitis C infections are the cause of approximately 20% of all
cases of hepatitis and are responsible for 8000 to 10,000 deaths in the United States each
year.3 Hepatitis C is also the most common cause of hepatic cancer (approximately 30%
of all cases) and the leading indicator of a need for liver transplant.4
PATHOPHYSIOLOGY
Hepatitis C is caused by the hepatitis C virus. The hepatitis C virus is an RNA virus.
RNA viruses (HIV, hepatitis C, Ebola, dengue, influenza, etc.) have very high replication
rates, they are genetically very diverse, and they have a very high rate of mutation, a
mutation rate that is several orders of magnitude greater than DNA-based viruses and
organisms.5
One of the reasons why RNA viruses mutate so intensely and are so genetically diverse
is that these viruses have quasispecies. Quasispecies are variants of the virus with small –
but very significant – molecular variations, and it is thought that quasispecies were
developed by viruses as a survival tactic. By constantly producing new and different
“profiles,” the virus can ensure its survival against the body’s immune system and drugs.
There are six major hepatitis C genotypes – genotypes 1 through 6 – and there are
more than 100 subspecies.6 The most common genotype worldwide is type 1, and this is
the most common genotype in the United States: approximately 72% of all patients in the
United States with a hepatitis C virus infection have the type I genotype of the virus.
Genotype 2 (an incidence of approximately 15%) and genotype 3 (an incidence of
approximately 7%) are much less common in the United States. Genotypes 1a and 1b are
very common in the United States.7
Learning Break: Hepatitis C virus has six major genotypes, there are more than 100
subtypes of the virus, and it replicates and mutates very rapidly. These facts have
enormous implications when clinicians are trying to eradicate the virus.
TRANSMISSION OF HEPATITIS C
The most common mode of transmission of hepatitis C is by exposure to infected
blood.8 This happens most often – in developed countries – because of intravenous
drug use. The CDC has estimated that 33% of people between the ages of 18-30 who use
IV drugs are infected with hepatitis C, and the rate of infection is approximately 70% 90% in older person who used, or still use IV drugs.9 IV drug use is by far the most risky
behavior in terms of being infected with the hepatitis C virus; the rate of transmission of
the virus is much higher than with any other mode of transmission.
Learning Break: Syringes used by people who are intravenous drug users have been
tested, and the hepatitis C virus can persist in the syringe for many weeks, even when the
syringe is subjected to relatively extreme temperatures.
There are other modes of transmission of hepatitis C. Most are uncommon, but some
can be important in certain situations.

Blood transfusion: Hepatitis C can also be spread by blood transfusion, but with
greater awareness of the prevalence of the disease and better screening techniques
of blood supplies, the risk of this is extremely low – perhaps 1 case of
transmission for every 2 million tranfusions.10,11

Hemodialysis: Patients who undergo maintenance hemodialysis have a much
higher rate of hepatitis C infection than the general population, and these patients
and the population of IV drug users account for the greatest number of hepatitis C
infections in developed countries.12,13 The majority of the cases of hepatitis C
infection associated with hemodialysis appear to be caused by poor technique and
poor compliance with sterility precautions and protocols by dialysis unit
personnel.14,15 Hepatitis C has been reported to be transmitted during medical
procedures such as endoscopy, colonoscopy, etc., but the transmission rates in
these situations are very low.

Pregnancy: The hepatitis C virus can be transmitted from an infected mother to
the fetus, but the rate of transmission is considered to be low, approximately 2% 6%.16 If the viral load is high, the mother has an HIV infection, there are perineal
lacerations during delivery, there is a prolonged rupture of the membrane, or an
amniocentesis was performed, the risks are higher.17 The virus can be found in
breast milk, but breastfeeding is not contraindicated.18

Sexual transmission: The information on sexual transmission of hepatitis C is
confusing and contradictory. Hepatitis C can be detected in tears, semen, and
saliva, but the rate of sexual transmission of the virus is thought to be very low. If
both sexual partners are in a long-term, monogamous relationship, the risk of
hepatitis C sexual transmission is thought to be approximately 0% - 0.6%, and the
CDC does not recommend the use of barrier protection for these couples.19,20 One
recent study that examined the medical literature concluded that there is no risk of
sexual transmission of hepatitis if partners are in a monogamous relationship.21
However, if the infected partner or partners has used IV drugs, has had > 20
sexual partners, or if the couple engages in violent sexual activity, the risk of
sexual transmission increases.22 There are reports of sexual transmission in which
these and other risk factors are absent, but the rate of transmission is very low,
and these cases may be due to unreported/under-reported IV drug use. Hepatitis
C infections in men who have sex with men are common if the participants also
have an HIV infection (hepatitis infection rates reported in this population to be
approximately 9.4% to 17.8%),23,24 The incidence of hepatitis C infection among
men who have sex with men but who do not have an HIV infection has been
reported to be equivalent to the incidence of the hepatitis C infection in the
general population.25

Other forms of drug use: Insufflation of drugs (snorting) has identified as a route
of transmission of hepatitis C.26

Family transmission: The risk of being infected with the hepatitis C virus is
higher among people who are living with someone who has the virus then those
who are not.27,28 The risk is not high, however, and these infections most likely
happen when family members share toothbrushes, nail clippers, inhalants, etc.,
Hepatitis C cannot be contracted by sharing utensils, touching, coughing,
sneezing, and other causal contact. It is not transmitted through insect bites, food,
or water.

HIV infection: The incidence of hepatitis C infection is much higher among men
who have sex with men and who also have an HIV infection. This may be due to
sex practices that increase the risk of exposure to contaminated blood, a higher
rate of IV drug use among this population, or an unknown factor.29,30

Other causes: The risk of transmission of hepatitis C due to a needle stick is
approximately 1.8% - 3%.31 In about 10% of all cases of hepatitis C infection, no
mode of transmission can be identified.32
NATURAL HISTORY OF HEPATITIS C INFECTION
Hepatitis C causes inflammation and fibrosis of the liver. In approximately 15% - 25 %
of all people infected with the virus it is spontaneously cleared, although there is
evidence that the spontaneous clearance rate can at times be as high as 50%.33,34
However, it is clear from the published literature that most people infected with hepatitis
C develop chronic hepatitis.
If the hepatitis virus is not spontaneously cleared, the natural history of those infected
has been well doucumented.35 Approximately 80% of those infected will develop a
chronic, stable infection and it will not affect the person’s health. The other 20% will
develop cirrhosis and fibrosis; the extent of the cirrhosis and fibrosis depends on use of
alcohol (more than three drinks/50 grams of alcohol a day) age, sex, obesity, presence of
diabetes, and co-infection with other viruses. Most of these people – 75% - will have a
clinical course that is slow and progressive, while the other 25% will develop liver failure
or liver cancer. This means that the risk of developing liver failure or liver cancer is
approximately 1% - 4%.
Learning Break: The treatment for hepatitis C is takes 11 months, it is expensive, it
causes numerous uncomfortable and potentially serious side effects, and for many
patients there not a very good chance it will work. Most people with a hepatitis C
infection will not die from the disease, but liver cancer is a grim diagnosis. It would be
extremely useful to be able to predict who will develop liver failure and/or cancer so that
those who will benefit from the treatment and those who won’t could be clearly
identified. This is not possible at this time, but if the patient with a hepatitis C infection
abuses alcohol or uses IV drugs, has an HIV infection or a hepatitis B infection, has
hemochromatosis (deposition of hemosiderin, an intracellular form of iron), developed
the infection later in life, is male, has diabetes, or is infected with genotype 1B, there is a
greater chance of developing liver cancer.36,37
DIAGNOSING HEPATITIS C
Most patients with hepatitis C have chronic stable infections that do not affect their
health and they have no signs or symptoms. People with cirrhosis can have fatigue,
malaise, nausea, vomiting, peripheral edema, jaundice, and ascites. The liver
transaminases may be normal (even if there are serious hepatic lesions) or they may
be elevated, and they tend to fluctuate.
Learning Break: Because many people with a hepatitis C infection may not be aware
they are carrying the virus, it is important that people who have a high risk of being
infected are screened. This would include: people who do, or have used IV drugs, people
with an HIV infection, people who received blood products or organ transplants before
1992, children born to a mother with a hepatitis C infection, people who received clotting
factor products prior to 1987, and people who receive maintenance dialysis.
Learning Break: It is not recommended that the general population – i.e., people without
specific risk factors for contracting hepatitis C – who are asymptomatic be screened for
the virus.
The definitive tests that will confirm an infection with hepatitis C and let the clinician
know what type and how widespread the infection are a) an anti-HCV antibody
screening that detects antibodies against the core protein of the virus, b) if the anti-HCV
test is positive, it is recommended to perform a recombinant immunoblot assay (RIBA)
to confirm the infection , and c) viral load and viral genotyping.38 In certain
circumstances (an early infection, or people who cannot make antibodies against the
virus), the anti-HCV antibody test may be negative even if the person is infected, and a
polymerase chain reaction (PCR) test for hepatitis C RNA should be obtained.
Learning Break: The RIBA test is recommended to confirm the diagnosis because in
certain circumstances the test for anti-HCV antibody can yield a false positive.
Learning Break: Viral load actually measures hepatitis C virus RNA. The viral load
fluctuates considerably over time, and an increase or decrease does not have any clinical
significance. Also, the viral load is often referred to as “high” or “low,” and any
measurement > 800,000 copies per IU/mL is considered high. However, a high viral load
is not a completely reliable indicator that the patient will develop cirrhosis or cancer.
When an infection has been confirmed, an ultrasound examination of the liver is done
to look for evidence of tumors, cysts, etc. Ultrasound has been shown to be useful for
detecting early-stage liver cancer.39
A liver biopsy can also be performed to assess the degree of inflammation and fibrosis.
It can also help to discover and/or rule out other disease or pathologies. Unfortunately, it
is possible that the tissue samples may not accurately represent the true extent of
inflammation and fibrosis, and as with all such procedures, there can be errors by the
pathologist.40 There are also complications (bleeding and infections), but these are very
uncommon. At this time, although there is some controversy concerning its usefulness,
liver biopsy is still considered to be the gold standard test for evaluation of the
extent of fibrosis and cirrhosis in patients with a hepatitis C infection.41,42
Other tests have been investigated for assessing liver inflammation and fibrosis in
patients with hepatitis C. Transient elastography has been used as a non-invasive way
of detecting the presence and/or extent of liver fibrosis. This technique uses an ultrasound
that produces vibrations that “bounce” off the liver. By measuring the degree of rebound
of these vibrations from the liver, elastography is able to determine how “stiff” the liver
is which in turn reflects the degree of cirrhosis. It appears to be an accurate technique –
and compares well with liver biopsy – for these purposes.43,44
FibroTest (FT) is a measurement of five blood levels: alfa2-macroglobulin,
apoliporoteinA1, haptoglobin, GTT, and bilirubin. It has been shown to compare
favorably with liver biopsy for identifying cirrhosis and predicting five-year
mortality.45,46 Another blood test that has been used to assess fibrosis is the Enhanced
Liver Fibrosis (ELF) test. This is a combination of three markers of fibrosis: hylauronic
acid, amino-terminal propeptide-of-Type III collagen, and tissue-inhibitor of matrixmetaloproteinase-1, and like the FibroTest it has been shown to be as effective (compared
to liver biopsy) and it is probably superior (compared to transient elastography) for
detecting liver fibrosis.47
Learning Break: The blood components measured in the FibroTest and ELF are matrix
components of liver cells, and various hepatic enzymes.
Liver fibrosis caused by hepatitis C is often staged in categories of 0/1 (no fibrosis or
early fibrosis), 2 (intermediate), and 3/4 (advanced).48 Other rating scales exist (e.g., the
Ishak scale, the Knodell histologic activity index) that measure the extent of the disease
and the degree of fibrosis.
COMPLICATIONS OF HEPATITIS C
Aside from cirrhosis and liver cancer, there are many other complications that have
been associated with hepatitis C infections. Some of these are clearly caused by the
disease (e.g., cryogobulinemia), others are strongly liked to hepatitis C (e.g., lichen
planus), in some the associations with hepatitis C have been confirmed (e.g., diabetes
mellitus), while for the association between the disease and hepatitis C gas been made
only on the basis of anecdotal observations (e.g., rheumatoid arthritis).49

Diabetes: There is clinical and experimental evidence that indicates that an
infection with the hepatitis C virus affects glucose metabolism and that patients
infected with the hepatitis C have a higher incidence of type 2 diabetes than the
general population.50 It appears that even after controlling for factors such as age,
obesity, etc., the presence of a hepatitis C infection is an independent factor that
increases the risks for developing type 2 diabetes; in several studies this risk has
been estimated to be two- to seven-fold.51
Learning Break: Type 2 diabetes and insulin resistance appear to worsen the clinical
progress of hepatitis C infections and reduce the effectiveness of therapy.52,53

Non-Hodgkin’s lymphoma: Non-Hodgkin’s lymphoma has been reported in
about 5% - 8% of all patients with a hepatitis C infection, and the risk of
developing non-Hodgkin’s lymphoma may increase approximately threefold in
patients with a hepatitis C infection.54,55

Dermatological complications: Lichen planus is an inflammatory skin disease
that is characterized by, pruritic, papular, scaly lesions. It has been suggested that
lichen planus can be caused by hepatitis C, and there is evidence that the disease
is much more common among people with a hepatitis C infection.56,57 The signs
and symptoms can be very annoying and irritating, but it is not a dangerous
disease and does not cause serious or permanent harm. Porphyria cutanea tarda
(PCT) is another skin disorder that has been strongly associated with hepatitis C
infection. This disease is caused by reduced activity of a specific enzyme that is
involved in the heme synthesis pathway.58 Porphyria cutanea tarda is manifested
by photosensitive erythema, fragile skin, skin erosions, blisters, and scarring. The
disease is very common among people with hepatitis C; one study estimated
found that approximately 50% of all patients with a chronic hepatitis infection had
porphyria cutanea tarda.59 Infected skin lesions that heal slowly and scarring are
common in patients with porphyria cutanea tarda.60 It has also been noted that
patients with this disease are more likely than the general population to develop
liver cancer, but this association has not been proven 61

Renal disease and hepatitis C: Kidney disease has been associated with hepatitis C
infection, and the most common type of renal disorder seen in patients with a
hepatitis C infection is membranoproliferative glomerulonephritis
(MPGN).62,63 Membranoproliferative glomerulonephritis is a form of nephritis
that is caused by a specific pattern of glomerular injury, and it can result in
nephrotic syndrome, azotemia, and hematuria. The disease is a relatively common
complication of hepatitis C: the incidence has been estimated to be approximately
40%.64,65

Cryoglobulinemia: Cryglobulinemia is the most common extrahepatic
complication of hepatitis C infection.66 The disease is immune-mediated. It is
characterized by deposition of immune complexes into the endothelium of small
and medium-sized arteries and veins. This cause a widespread inflammation and
vasculitis.67 The estimates of the prevalence of cryoglobulinemia in patients who
have hepatitis C very considerably and range from 10% to 70%.68 The disease
appears to be an independent factor that increases the risk of developing cirrhosis,
and all of the hepatitis C genotypes are equally affected.

Thyroid disease: Thyroid disease is relatively common in patients with a hepatitis
C infection. One author noticed a 13% incidence of thyroiditis in the patient
population infected with hepatitis C; the incidence was 7% in the patients who
were not infected with the virus.69 Antonelli et al found a much higher incidence
(2% versus 0%) of thyroid cancer in patients with hepatitis C, and a higher
incidence of hypothyroidism.70,71

Pulmonary fibrosis: Pulmonary fibrosis is a complication of chronic hepatitis C
infection. The approximate incidence of the disease in this patient population
varies widely (0.04% to 13%) and there is some controversy as to whether there is
a true cause and effect relationship.72,73,74

Atherosclerosis: Some researchers have noted the presence of a hepatitis C
infection increases the risks for developing coronary and carotid
atherosclerosis.75,76
Learning Break: The patient with a chronic hepatitis C infection has a heightened
immune response, and this response to the infection appears to be the cause of the
complications. There is evidence that strongly suggests that the type 2 diabetes, renal
disease, thyroid disease, etc. are immune complex-associated diseases, i.e., autoimmune
diseases.77
The complications explained here are the most common ones and those for which there
is either proof and/or very strong evidence for a cause and effect relationship. There have
been case reports that have reported an association between hepatitis C and these
diseases: psoriasis, chronic polyarthritis, rheumatoid arthritis, polyartheritis nodosa,
Bechet’s syndrome, fibromyalgia, chronic urticaria, chronic pruritus, vitiglio, Kaposi’s
pseudo-sarcoma, cardiomyopathies, corneal ulcer, erectile dysfunction, necrolytic acral
erythema, peripheral and central neuropathies, and poly/dermatomyositis.78
TREATMENT OF HEPATITIS C
There is no vaccine for hepatitis C so prevention of the disease is based on avoiding
risk factors. In the event of an accidental exposure such as a needle stick, there is no solid
evidence that treating with immune globulins or the standard hepatitis C protocol will
prevent an acute infection from becoming chronic.79 (Remember: the risk of this
occurring is very small).
Whether or not to treat a patient with chronic hepatitis C can be a difficult decision.
Most people do not succumb to the disease, the duration of the therapy is long, the
adverse effects are very unpleasant and at times dangerous, and there is no guarantee of a
cure. However, most authorities recommend at least a trial of therapy for those patients
who have a chronic infection, who have some evidence of fibrosis or cirrhosis, who have
normal renal function, and who do not have a history of anemia or neutropenia. Once the
decision has been made to treat the patient with a hepatitis C infection, the goal of
treatment is to try and eradicate the virus and by doing so, prevent the progression to
severe liver damage and/or liver cancer.
Eradicating The Virus
The current standard treatment used to eradicate the hepatitis C virus is injections of
interferon and oral ribavirin.
Interferon (Pegasys® is a common brand name of the drug) is a synthetic version of
interferon, a naturally occurring glycoprotein. Endogenous interferon performs many
antiviral and immune functions, e.g., it stimulates the production of antiviral proteins that
inhibit viral replication, enhancement of natural killer activity, etc. Synthetic interferon
used to treat hepatitis C infections works by interfering with viral replication and
function.80
The synthetic interferon that is used today comes in two forms: peginterferon-α-2a
and peginterferon-α-2b. These drugs are pegylated: the interferon molecules have been
attached to a molecule of polyethylene glycol (the peg). This formulation decreases the
volume of distribution of the drug, increases the drug half-life, and reduces its
clearance.81 Clinical evidence has clearly shown that because of these pharmacokinetic
qualities, the pegylated interferons have significantly increased response to treatment
compared to unmodified interferons when they are used as monotherapy or with
ribavirin.82 The pegylated interferons are administered via injection, subcutaneously,
once a week.
Learning Break: Although more research needs to be done, there is a lot of evidence
that suggests that peginterferon-α-2A is more effective than peginterferon-α-2b.83
Ribavirin (Rebetol® and Copegus® are common brand names) is an oral medication
that interferes with viral replication and modulates the body’s immune response.84
Ribavirin eradicates the hepatitis C virus and it also decreases liver inflammation caused
by the infection. Combining pegylated interferon with ribavirin is a much more effective
way to treat hepatitis C virus infections. When the two drugs are used together, the
sustained virologic response (SVR; this will be explained later) is twice that of what can
be attained using either drug alone.85 Ribavirin is an oral tablet, and the usual dose is 800
mg to 1200 mg a day, given in two doses.
The duration of the treatment with interferon and ribavirin depends on the patient’s
genotype and response to therapy. Patients with genotype 1 and 4 are treated for 48
weeks. Patients with genotype 2 and 3 are treated for 24 weeks. In both groups, the
response to therapy is evaluated several weeks after its start. If the hepatitis C RNA is
undetectable or there has been a 2-log-fold decrease in RNA, the therapy should be
continued for the full course. If there is no significant response, the treatment should be
stopped as there is almost no chance it will be successful even if the full course is
administered.86
The effectiveness of the interferon/ribavirin combination is variable and depends on
patient factors (i.e., age < 40 is beneficial, presence/extent of cirrhosis, a low viral load,
female gender, no use of alcohol, etc) but success of the therapy probably depends, for
the most part, on the genotype. The genotypes 2 and 3 are much more treatable: the
expected success rate for treating genotypes 1 and 4 is approximately 30% - 50% while
the expected success rate for treating genotypes 2 and 3 is approximately 80%.87,88
Effectiveness of therapy is defined as SVR, and SVR is defined as absence of
detectable hepatitis C RNA at the end of the treatment and at six months after the
end of the treatment.
Learning Break: Sustained viral response is not just a laboratory value. Attaining a
SVR has been clearly shown to decrease the risk of developing liver cancer and
reduce the mortality associated with hepatitis C.89,90 There is also evidence that SVR
is durable. Several studies noted a very high incidence of patients remaining virus-free
for up to 7 years.91,92
Learning Break: Some people who become infected with the hepatitis C virus do
spontaneously clear it. However, researchers found that early treatment was associated
with a higher rate of SVR, and they recommended that patients who contract the infection
be treated quickly and aggressively. The longer the wait after the infection before
treatment is started, the lower the rate of SVR.93
Prior to treatment, serum blood urea nitrogen, serum creatinine, complete blood count,
liver transaminases, serum glucose, and serum thyroid studies should be obtained.
Patients should also be tested for the presence of HIV, hepatitis B and hepatitis A.
Contraindications to interferon/ribavirin therapy include: sickle cell anemia, thalassemia
major, pregnancy, breastfeeding. hepatitis, severe liver disease, and renal disease.
Learning Break: Renal function, bone marrow function, endocrine function, and liver
function must be evaluated before starting therapy with interferon/ribavirin and during
therapy with these drugs as both the disease and the treatment can affect the kidneys,
bone marrow, the thyroid, and the liver.
The adverse effects of interferon/ribavirin therapy are numerous. The most common
adverse effects cause significant discomfort, but they are not dangerous and will resolve
once therapy has been stopped. However, there are some adverse effects associated with
these drugs that have (rarely) serious consequences. Unfortunately, aside from these
potentially serious adverse effects, the level of discomfort patients experience from these
“minor” adverse effects is such that many stop therapy.

Minor adverse effects: Arthralgias, fatigue, malaise, myalgias, fever, cough,
itching, rash, diarrhea, pruritus, mouth ulcers, injection site pain, anorexia,
nausea, emotional lability. Many of these are quite common and will affect up to
90% of all patients taking the therapy.94

Major adverse effects: Anemia, neutropenia, thrombocytopenia, significant
depression, suicide, hypothyroidism, and retinopathy have been reported. The
hematological complications are relatively common: up to 50% of patients
treated with interferon/ribavirin will develop neutropenia, up to 48% will develop
thrombocytopenia, and up to 34% will develop anemia.95 These effects are the
most reason (aside from the patient’s inability to tolerate the less serious adverse
effects) that interferon/ribavirin therapy is stopped. Anemia, neutropenia, and
thrombocytopenia can be managed with dose reductions or drugs that stimulate
the bone marrow, and these values will return to normal once the
interferon/ribavirin therapy has been stopped.96,97
Learning Break: Depression is a very common adverse effect caused by
interferon/ribavirin: the incidence of depression has been reported to be as high as 66%.98
Suicidal ideation is common, but suicides are rare.99 Nonetheless, many patients taking
interferon and ribavirin will need antidepressant medication and/or psychiatric
counseling.100,101
HEPATITIS C AND THE PATIENT WHO IS HIV POISTIVE
Approximately 30% - 50% of people with an HIV infection are infected with hepatitis
C.102 Patients with HIV and hepatitis C infection have a much higher risk of developing
liver cancer, and these patients do not respond to interferon/ribavirin therapy nearly as
well as the HIV-negative population with a hepatitis C infection.103 The response rate to
interferon/ribavirin in patients infected with HIV is approximately ½ the response rate of
the patients who are HIV-negative, and relapses after viral clearance are more frequent.104
NEW TREATMENTS FOR PATIENTS WTH HEPATITIS C
The success rate of the interferon and ribavirin treatment for hepatitis C genotype 1 –
the most common genotype in the United States – is relatively low. However, the FDA
has recently approved two drugs that have been shown to dramatically increase clearance
of the hepatitis C virus.
These drugs – boceprevir and telaprevir – are direct acting antiviral agents. These
drugs, when used with the standard interferon and ribavirin therapy, have been shown to
produce a high rate of response in patients who have relapsed after standard therapy and
patients who did not respond to standard therapy105 and a sustained virologic response of
up to 75% has been reported.106
Boceprevir (brand name Victrelis™) and telaprevir (brand name Incivek™) are both
protease inhibitors. Protease inhibitors prevent viral replication by inhibiting the activity
of proteases. Proteases are enzymes that accelerate the cellular production of proteins that
is induced by a virus when it enters a cell. Viruses need these proteins to replicate, and
the protease inhibitors block activity of the protease enzyme.107 Boceprevir and telaprevir
are prescribed as follows:

The treatment protocol for boceprevir starts with four weeks of interferon and
ribavirin therapy, then boceprevir is started. In patients who are treatment naïve,
the viral load is checked 8 weeks from the start of the therapy. If the viral load is
zero, all three drugs are continued until 24 weeks of therapy have been received,
then the viral load is checked again If it is zero, therapy is stopped. If there is any
detectable viral load during the period of 8 weeks to 24 week of therapy (the viral
load will be checked at 8 weeks, 12 weeks and 24 weeks), all three drugs are
given until 36 weeks of therapy have been received. At that point the boceprevir
is stopped but the interferon and ribavirin are continued until 48 weeks of therapy
have been received. Patients who have previously been treated for hepatitis C and
have a zero viral load between weeks 8 and 24 should receive all three drugs for
36 weeks; if the patient has a detectable viral load during the period of 8 weeks to
24 weeks of therapy, he/she should receive all three drugs for 36 weeks and then
be treated with interferon and riabvirin until 48 weeks of therapy have been
completed.108 Boceprevir is an oral medication, the dose is 800 mg, and it is taken
three times a day with a light meal or snack.
Learning Break: Boceprevir has many of the side effects associated with interferon and
ribavirin therapy. Anemia and neutropenia are very common, as are alopecia, arthralgia,
chills, diarrhea, dizziness, fatigue, insomnia and nausea, etc. Dysgeusia (alteration in
taste) is a common (incidence of approximately 32%) side effect of the drugs that is not
caused by telaprevir. There are some drugs of several classes of commonly used
medications (e.g., anticonvulsants and anti-tuberculars) that that should not be used in
patients receiving boceprevir. Also, boceprevir is a strong inhibitor of the CYP34A/5 and
the P-gp drug metabolizing enzymes, and there are many common drugs such as calcium
channel blockers, digoxin, and warfarin that are primarily metabolized by these enzymes.
Concurrent use of boceprevir and one of these drugs (See the Victrelis™ package insert
for the complete list) could cause dangerously elevated plasma levels of digoxin etc. If a
patient is receiving boceprevir, always check the boceprevir prescribing information
before giving other medications.

The dosing for telaprevir is 750 mg taken orally three times a day with food (not
low-fat foods). In treatment-naive patients or patients who patients who relapsed
from previous therapy, telaprevir, interferon, and ribavirin are given for 12 weeks.
The viral level is measured 4 weeks after therapy has been started and 12 weeks
after therapy has been started. If the viral load is zero both times, the telaprevir is
stopped and the interferon and ribavirin are continued for 12 more weeks. If there
is a measurable viral level at week 4 or week 12, the telaprevir is stopped, and the
interferon and ribavrin are continued for 36 more weeks. For patients who have
been treated before and had no response or a partial response, telaprevir,
interferon, and ribavirin are given for 12 weeks, the telaprevir is then stopped, and
the interferon and ribavirin are continued for 36 more weeks.109
Learning Break: Some of the common side effects of telaprevir are anemia, diarrhea,
fatigue, pruritus, and rashes. As with boceprevir, telaprevir is a potent inhibitor of several
drug metabolizing enzymes, the cytochrome P450 enzyme CYP3A and the P-gp enzyme,
and the plasma level of commonly used drugs such as amiodarone, digoxin, and warfarin
that (see the Incivek™ package insert for the complete list) that are primarily metabolized
by these enzymes could become dangerous. If a patient is receiving telaprevir, always
check the telaprevir prescribing information before giving other medications.
The sustained viral response rate of the respective drugs is similar. Anemia is more
common as a side effect of boceprevir
LIVER TRANSPLANTATION AND HEPATITIS C
End-stage liver disease caused by hepatitis C is the most common indication for liver
transplantation in Westernized countries.110 However, the results of liver transplantation
for patients with hepatitis C are not very hopeful. The natural progression of hepatitis C,
the progression of cirrhosis caused by hepatitis C, and the progression of decompensation
to death are actually accelerated after liver transplantation: more than 40% of all patients
infected with hepatitis who receive a liver transplant develop cirrhosis, and histologic
features of a chronic carrier of hepatitis C are seen in 90%-95% of all patients within five
years.111 These effects are rare if the organ recipient has cleared the hepatitis C virus prior
to the transplant. In patients who still have circulating virus, the graft is infected during
the transplantation procedure. Factors that increase the risk of liver failure, cirrhosis, etc.
after liver transplantation include a) a high viral load in the serum and the liver, b)
genotype 4 infection (possible but not confirmed), c) female gender, and d) host immune
response.112
NURSING CARE OF THE PATIENT WITH A HEPATITIS C INFECTION
Nursing care of the patent with hepatitis C should focus on patient education,
emotional and psychosocial support, and monitoring the patient for adverse drug effects
and the signs and symptoms of complications of the disease.
Patient Education
Patient education is a crucial part of caring for the patient with hepatitis C. The patient
will need to have the information necessary for understanding and coping with a chronic,
potentially serious illness. Specifically, the patient needs information about hepatitis C
transmission, living with others (what behaviors are safe, what behaviors are not in terms
of transmission), and self-monitoring for signs and symptoms of complications of
hepatitis C. The patient will also need information about lifestyle issues (e.g., drug use,
alcohol use, sexual activity) that can affect his/her illness. The patient should receive
information, appropriate for his/her level of cognitive ability, about what the disease is
and what it means to be infected with hepatitis C.
When the decision has been made to use the interferon/ribavirin therapy, the patient
will need intensive support from the nurse because a great majority of these patients
will be treating themselves at home. The patient will need to be taught sterile technique,
injection technique, and the proper methods of disposing of hazardous material. The
patient will need to understand that taking these drugs is a serious commitment; those
patients with genotype 1 will need therapy for almost a year. He/she will need to
understand that many of the adverse effects can be very unpleasant, but are not serious
and can be managed with over-the-counter remedies or symptomatic care. But there are
some adverse effects (e.g., neutropenia) that can have some very harmful consequences
and require dosage adjustments or prescription drugs, and this must be stressed. The
patient must also know that the therapy will require frequent doctor’s office visits and
phlebotomies.
Emotional and Psychosocial Support
Having a disease such as hepatitis C is a frightening experience. There is a real risk of
disability or death. The treatment protocol is very difficult and it is not guaranteed to
work. Patients who are receiving the interferon/ribavirin must many times resign
themselves to the fact that they will feel tired, weak, nauseated, etc. for almost a year. In
addition, they will have to learn to treat themselves at home, and some patients find that a
daunting task. These patients will obviously need a lot of emotional and psychosocial
support. This support will help the patient cope with the illness and the adverse effects,
but it also has a very practical benefit. Many patients who stop the interferon/ribavirin
therapy protocol do so because they cannot tolerate the therapy. A skilled and
knowledgeable nurse can help these patients with practical tips on how to cope with these
adverse effects. The nurse can also offer emotional support. By being able to offer reallife solutions for coping physically and psychologically, the nurse can help the
patient receiving the interferon/ribavirin therapy to “stay the course” and complete
the treatment. The nurse may often be the first caregiver to notice the presence of
depression in these patients, and can notify the physician and encourage the patient to
seek help.
Monitoring for Adverse Drug Effects and Complications of the Disease
Monitoring for adverse drug effects and complications of the disease is not difficult.
The nurse must be aware of the most common adverse drug effects and complications of
the disease, know which ones are minor and which ones can be potentially serious, and
be able to understand the difference between the two. For example, it is quite normal fro
a patient who is receiving interferon/ribavirin to feel fatigued. However, when fatigue
progresses to a more serious lack of energy, it may indicate anemia and the physician
should be notified. It is normal for the patient receiving interferon to have a cough and
some dyspnea, but if the cough is productive and the dyspnea interferes with simple
activities of daily living, these might be signs that indicate the presence of an infection
and/or pulmonary fibrosis.
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