Denise RobinsonLake Worth High School

April 10, 2010

FAU Medical Outreach Program

Hepatitis C “The Silent Epidemic”

Table of Contents

Basic Anatomy of Effected Organs and Basic Structure of A Virus 3

Etiology 6

Signs and Symptoms 7

Diagnosis 8

Treatment 11

Prognosis 12

Prevention……………………………………………………………………………………......15

2

Hepatitis C is a spherical, single-stranded RNA virus that, over a long period of time,

affects the entire body. Before giving an explanation of the virus and how it works, a breakdown

of the anatomy of the affected organs must be given. First of all, the word “Hepatitis” means

inflammation of the liver which makes the liver, not only a perfect place to start, but also the

basis of the disease. Weighing about three pounds in an adult, the liver is located in the upper

third of the abdomen, resting “on the stomach, the intestines, and the right kidney” (Horn, 2005,

p. 25). “About 13% of the body’s blood is in the liver” (Horn, 2005, p. 29). Eighty percent of

the blood that travels from the heart into the liver goes through the portal veins; the other twenty

percent enter through the hepatic artery. The deoxygenated blood is then returned to the heart

through the hepatic vein (Horn, 2005).

“The liver performs more than 500 important functions” (Horn, 2005, p. 30). One of its

most important jobs is to be the body’s filter. Without it, our blood would be clogged with fats;

there would be no way to get rid

of the toxins in our body, and the

breaking down of food wouldn’t

even be possible. Edible

products that have the ability to

travel within the bloodstream,

“must first flow through the

liver” (Horn, 2005, p. 27). The

liver produces a greenish

substance called bile which carries toxins away from the liver. Bile is efficiently collected from

the liver cells through the hepatic bile duct system. About half of the bile that is produced is

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delivered by the common bile duct to the small intestine. The other half is sent straight to the

gallbladder which acts as a storage unit for the bile (Horn, 2005, p. 29). Once fatty foods are

consumed, the gallbladder “squirts” bile into the small intestine so it can help break down the

fats (Zein and Edwards 3).

The liver has other important functions as well. For one thing, it helps fight off infection

by “secreting some immune factors that help the cells of the immune system fight infections”.

Removing and killing bacteria within the blood and producing certain chemicals used for

coagulation or blood clotting when tissue is destroyed are essential functions as well (Horn,

2005, p. 31).

The liver is divided into right and left lobes. These main lobes are divided into two more

lobes which are then “further subdivided

into many thousands of basic functional

units or small lobes called lobules” (Horn

29). The lobules appear to be in a

hexagonal shape and at each corner of the

hexagon are “a cluster of three vessels: very

small branches of the hepatic artery, the

portal vein, and a small bile duct” (Horn

29). A central axle lies in the center of the lobule and branching out from it are spokes. These

spokes are made up of hepatocytes or liver cells. The hepatocytes are the workers of the liver.

Their job is to take certain substances from the blood, modify them, and put these modified

substances either back into the blood or into the bile ducts (Horn, 2005, p. 29).

4

Not only is the anatomy an important part of understanding the overall damage that is

caused by a virus, but also an understanding of the term, virus, in general must be met. What is a

virus? A virus is a microscopic parasite that is dependent on a host cell in order to replicate and

survive. The virus first attaches to the host cell, penetrates it, and inserts nucleic acid which

initiates the reproduction process, but instead of replicating the cell, the cell will make copies of

the virus. Once the new viruses are produced, they leave the host cell and search for new cells to

infect. The virus takes over the metabolic functions of the host cell and uses that energy to stay

alive. This energy that would normally be used to meet the needs of the host cell and the needs of

other cells, is now being used as a deadly weapon and “the whole organism may develop

symptoms that are caused by the loss of important cell functions” (Horn, 2005, p. 44-45).

“Viruses have relatively simple structures” (Horn

45). They have nucleic acids and one way that scientists

classify viruses is whether they have DNA or RNA.

These nucleic acids usually have about 20 or fewer genes.

Another way to classify viruses is the number of strands

they have: a single or a double (Horn, 2005, p. 45). The

nucleic acid of a virus encased in a capsid is called a

nucleocapsid and the capsid protects the virus from

enzymes (Horn 45, 48). “Many viruses have spikes of

protein that make the capsid look like a pincushion”

(Horn 47). These spikes contain the special sites that allow it to recognize a host cell and “bind

to the surface” (Horn 47). When the virus is ready to leave the host cell, it exits through a

process called budding. This is when the virus comes out of the cell and the cell membrane

5

closes around the capsid until “until finally the membrane breaks free of the cell and closes up

with the virus inside” (Horn 50). However, some viruses have another exit strategy: they break

or rupture the membrane by releasing certain enzymes. “The completer virus structure that exits

a host cell and can infect other cells is referred to as a virion” (Horn 52).

Etiology

Having explained the basics, it’s best to start talking about the actual disease: Hepatitis C,

also known as the Silent Epidemic. Believed to have begun infecting humans as early as 1960,

HCV was formerly called non-A, non-B hepatitis and labeled as a “unique virus” (Fabry and

Narasimhan, 2007, p. 4). 170 million individuals worldwide have HCV and 4 million of those

are in the United States, most with chronic HCV (Fabry and Narasimhan, 2007, p. 8). Hepatitis

C primarily attacks the liver meaning that “roughly over half of all liver transplants in the United

States now involve patients with hepatitis C” ((Fabry and Narasimhan, 2007, p. 8).

Contracting the HCV begins with a simple transmission (Horn 86). HCV is a bloodborne

virus; therefore, the most common way to become infected with HCV is by it being directly

introduced into the bloodstream. “A history of Intravenous Drug Use (IVDU) is the most likely

cause of the infection in 60 percent of newly identified cases” (Fabry and Narasimhan, 2007, p.

16). IVDU, or intravenous drug use, is when the drug is injected directly into the bloodstream by

use of a needle. As the history of injections

lengthens and the sharing of needles increases, so

does that person’s risk of becoming infected (Fabry

and Narasimhan, 2007, p. 16). Until HCV was

discovered in 1989, blood transfusions were “a

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common route of transmission” (Fabry and Narasimhan 16). However once the virus was

identified, scientists began to do routine screening tests on donated blood. Due to the tests and

new technology, the risk of contraction has decreased from 1 in 100,000 to 1 in 1,000,000 (Fabry

and Narasimhan 16).

The most common ways of transmission are IVDU and blood transfusions, but according

to Zein and Edwards (2008), “intranasal drug use, as in the snorting of cocaine” (p. 29) is also a

common transmission. There are tiny blood vessels in the nose and when cocaine is snorted,

those vessels rupture giving the virus a perfect portal of entry. Some less common factors were

“infusion of clotting factor concentrates before 1987” (Fabry and Narasimhan, 2007, p. 16) and

“organ transplantation prior to 1992” (Fabry and Narasimhan, 2007, p. 16).

Signs and Symptoms

Signs are the things the doctor sees while symptoms are what the patient experiences

(Fabry and Narasimhan, 2007, p. 27). Sixty percent of patients around the world had no idea that

they even had the disease. The fact that these people didn’t know they even had the disease is

pretty common since most patients have no signs or symptoms of liver disease which is why it’s

called the Silent Epidemic (Fabry and Narasimhan, 2007, p. 27). Many people have no

symptoms for up to thirty years which is why numerous amounts of HCV patients are left

untreated; they don’t think there’s anything wrong. When someone thinks of liver disease, they

automatically think of the yellowing of the skin, or jaundice, which is due to the buildup of

bilirubin (Bruce and Montanarelli, 2007, p. 44), however, only about 20 to 30 percent of HCV

patients experience this symptom.

7

Other common, obvious symptoms are dark urine and/or a light stool due to the fact that

the liver is not filtering properly. Some patients will have symptoms like “fatigue, mild

discomfort over the liver, nausea, and a poor appetite” (Fabry and Narasimhan, 2007, p. 27),

however, these symptoms are vague and could be any number of things. Other reported

symptoms include “depression, joint pains, Irritable Bowel Syndrome, bloating, menstrual

difficulties, bruising and bleeding easily, itchy skin” (Bruce and Montanarelli, 2007, p. 43).

Individuals with chronic hepatitis C commonly experience inflammation of the liver

which leads to scarring. This permanent scarring of the tissue is called cirrhosis. Twenty

percent of chronic HCV patients who have progressed to cirrhosis have had the terrible fate of

liver failure and/or liver cancer, however, it is not immediate and might not even occur; the risk

is a 3 to 4 percent chance. “This risk is significantly higher in people who consume excessive

amounts of alcohol.”

Diagnosis

As previously stated, once HCV was identified and isolated, scientists began to do

routine screenings on donated blood in 1990 (Horn 88).

When it is apparent that the liver is not working properly, doctors will put the patient

through a series of liver function tests (LFTs) to measure “the levels of liver proteins, liver

enzymes (called transaminases, and cholestatic live enzymes), and bilirubin” (Edwards and Zein,

2008, p. 136). “Doctors

usually order a standard

group of tests called a

liver panel that includes

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aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline

phosphatase, and albumin” (Fabry and Narasimhan, 2007, p. 41). To find any inflammation or

injury in the liver, AST and ALT levels are tested. Elevated AST levels alone could mean

there’s an issue a few places in the body, however, if there are elevated ALT levels as well, there

is definitely an issue with the liver (Edwards and Zein, 2008, p. 136). Race and sex play a role in

the transaminase levels and just transaminase levels alone do not necessarily tell of the extent of

the liver damage; “they are only the first clues along a path of diagnostic tests employed to

pinpoint what is wrong” (Edwards and Zein, 2008, p. 136.) Bilirubin and albumin just measure

the level of liver function. When the bile ducts are clogged, alkaline phosphatase levels elevate.

Though liver function tests aren’t perfect, they do help to identify issues that the patient might

not have suspected (Fabry and Narasimhan, 2008, p. 41).

If HCV is already suspected to have infected a patient, then a direct test, also called

hepatitis C RNA tests, is usually given. This test looks for even the smallest amount of the

actual virus in the patient’s blood (Fabry and Narasimhan, 2007, p. 38). Hep C RNA tests are

either qualitative, declared as positive or negative, or quantitative, measuring the “amount of

virus in the blood”, depending on how it is reported (Fabry and Narasimhan, 2007, p. 39). The

quantitative tests are more helpful when deciding whether to continue treatment or not.

Currently the most common of the RNA tests is the polymerase chain reaction (PCR). The

results of the test are usually reported in international units per milliliter; “one international unit

is roughly equivalent to two copies” (Fabry and Narasimhan, 2007, p. 39).

When a patient is infected, HCV attacks the immune system (Fabry and Narasimhan,

2007,p. 40). As HCV is passed on from patient to patient, the virus evolves, meaning there are

numerous amounts of strands or genotypes of the virus which is “determined through a blood

9

test” (Fabry and Narasimhan, 2007, p. 40). “There are 6 major HCV genotypes and more than

50 subtypes” (Fabry and Narasimhan, 2007, p. 40) and these play a big part in predicting a

response to certain treatments. In the United States, 75 percent of HCV patients have genotype 1

and the most difficult to treat; the remaining 25 percent having genotypes 2, 3, or occasionally 4

which have more of a positive response to treatment. Genotype 5 is more prevalent in South

Africa and genotype 6 is commonly found in Southeast Asia (Fabry and Narasimhan, 2007, p.

40).

To further increase their knowledge of the patient’s condition, doctors will order an array

of radiological tests, the most common being an ultrasound. This produces an image of the

“gallbladder, kidneys, spleen, pancreas, and blood vessels” and allows the doctor to see the

severity of the liver’s abnormalities (Fabry and Narasimhan, 2007, p. 45). Though an ultrasound

isn’t flawless, if used in along with other patient information, it can be very useful for

determining the severity of the patient’s condition; it is also able to sometimes detect liver cancer

if it exists within the patient (Fabry and Narasimhan, 2007, p. 45).

In order to fully understand the liver’s degree of damage, doctor’s will ask for a liver

biopsy to be performed. A liver biopsy is when a physician sticks a needle into the liver and

extracts a small sample of the liver tissue. Once removed, the tissue is examined under a

microscope. If the ultrasound is not specific enough

and the LFTs were inconclusive, a liver biopsy has

the ability to clear things up and help eliminate other

sources of liver disease off the list (Fabry and

Narasimhan, 2007, p. 46). When interpreting a liver

biopsy, doctors will use a scale from 0 to 4 for the

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amount of inflammation and scarring in the liver where 0 is acknowledged as normal and 4 is

classified as cirrhosis (Fabry and Narasimhan, 2007, p. 48).

Prothrombin time (PT), yet another blood test, “reflects coagulation or the body’s ability

to clot” (Fabry and Narasimhan, 2007, p. 43).

Treatment

“The goal of treatment for hepatitis C is to prevent the development of cirrhosis and the

complications of cirrhosis including liver cancer and liver failure” (Fabry and Narasimhan, 2007,

p. 63).

Deciding whether or not to proceed with treatment, let alone choosing which treatment

would produce the best results is a delicate process and should not be rushed. It takes several

years for HCV to take its full affect and there is never a reason to start treatment in a hasty

manner. By the time the doctors have identified the true severity of the disease and begin

discussing different forms of treatment, patients have a definitive attitude about how they want to

handle their situation.

However, many people are

just as confused as ever and

spend a great deal of their

time throwing ideas around

in their heads, trying

desperately to make a

decision that is right for their

life style and family (Fabry and Narasimhan, 2007, p. 60).

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One treatment is therapy with interferon and ribavirin, however, due to the many

uncomfortable side affects this treatment is usually not recommended and/or most patients aren’t

candidates for it. The patients that do choose this treatment will have to “take an interferon shot

once a week and ribavirin tablets twice a day” (Fabry and Narasimhan, 2007, p. 61). Some of

the risks of this treatment are “depression, birth defects, infection, severe anemia, bone marrow

depression, thyroid disease, and worsening of an underlying autoimmune disease” (Fabry and

Narasimhan, 2007, p. 67). The length of time at which this treatment lasts is determined by the

genotype of the virus particular to the patient and the “amount of disease found on the initial

liver biopsy” (Fabry and Narasimhan, 2007, p. 61); it also depends on the genotype of the virus.

Once treatment begins, certain goals that have been set previously must be achieved as the doctor

checks the patient’s viral levels regularly (Fabry and Narasimhan, 2007, p. 70). If these targets

are not hit, the doctor will stop the treatment, reassess the situation and the patient’s condition,

and suggest alternate options. Patients infected with genotype 1 HCV are treated with 1,000 to

1,200 milligrams of peginterferon and weight-based ribavirin for 48 weeks, but will be halted if

the patient’s viral levels do not fall 100-fold by the 12-week mark or if the virus is still found in

the blood at the 24-week mark. Genotype 2 or 3 patients will receive 800 milligrams daily for 24

weeks and viral levels for these patients are not really checked since there is such high cure rate

for these genotypes (Fabry and Narasimhan, 2007, p. 71).

Many of the symptoms can be relieved by doing simple things like stress reduction and

having a healthier diet (Bruce and Montanarelli, 2008, p. 44).

Prognosis

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Now what the future holds for those with Hepatitis C depends upon the treatment and the

patient’s response to said treatment. There is a fine line between a treatment and a cure;

treatment is the process and the cure is the “destination”. Once HCV is no longer detected

during a number of blood tests 6 months after treatment has been stopped, “the outcome is

termed a sustained virological response (SVR)” (Fabry and Narasimhan, 2007, p. 62). Studies

show that once SVR has been achieved, there is a low chance that there will be a relapse or that

complications will develop (Fabry and Narasimhan, 2007, p. 62). If for some reason the patient

wants to stop treatment at any time, there really isn’t a risk. Obviously, continuing treatment for

the full length of time and taking the dosage prescribed by the doctor will increase the chance

that the patient will be cured. Occasionally, unwanted or risky side effects will become present

during treatment and at that time, the doctor may make the decision to cease treatment (Fabry

and Narasimhan, 2007, p. 76).

According to a study by Manns and colleagues, published between 2001 and 2004, (p.

72) the safety and efficacy of peginterferon alfa-2b with ribavirin was compared to interferon

alfa-2b and ribivirin; the cure rate was 54 percent. For patients with genotype 1 is 40 to 45

percent and 70 to 80 percent of those with genotype 2 or 3 (Fabry and Narasimhan, 2007, p. 72).

However, treatment protocols were different back during those years then they are now,

therefore, it is difficult to compare those results to this day and age. In another study by Fried

and colleagues in 2002, peginterferon alfa-2a and ribavirin combination was compared to

peginterferon alfa-2a; placebo showed similar results (Fabry and Narasimhan, 2007, p. 73).

“Genotype is clearly the most important predictor of a response to combination therapy” (Fabry

and Narasimhan, 2007, p. 74).

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There are several possible outcomes of treatment. The first, discussed earlier, is SVR.

Another is relapse where at the time that treatment ended, the virus was not detected within the

blood, however, six months later, it was present when blood tests were performed. This response

to treatment shows that the patient’s body was only able to rid itself of the virus temporarily.

Third, a patient has a huge drop in viral levels, but the virus is still detected in the bloodstream;

this patient is called a partial responder.

Finally, a rare but possible result is a nonresponder who is simply an HCV patient who is

not responding to the treatment that was given. In this case, the patient’s situation must be

reassessed because the treatment given was not able to clear the virus from the patient’s system.

It is important to acknowledge that though the virus isn’t gone, it’s promising that treatment has

slowed the virus’ journey through the body (Fabry and Narasimhan, 2007, p. 76-77).

Patients with mild scarring of the liver are not recommended any further treatment

because there is a little to no chance of developing cirrhosis. Appropriate lifestyle changes,

follow-up care every 6 to 12 months, and a liver biopsy every 3 to 5 years would benefit the

patient immensely (Fabry and Narasimhan, 2007, p. 77).

Those with more severe scarring or cirrhosis have a higher risk of developing

complications like liver cancer. There are really only two options for patients with this much

damage to the liver and are not responding to normal treatment. The first option is to consume a

“low dose of interferon is used indefinitely in an attempt to control (but not cure) the infection”

(Fabry and Narasimhan, 2007, p. 78). The other option is to use consensus interferon which is

under the brand name Infergen. It is a synthetic interferon made by combining natural

interferons and using the most common amino acid (Fabry and Narasimhan, 2007, p. 80). Since

2002, The North Dakota Department of Corrections and Rehabilitation has been using this type

14

of therapy on the prison populations where the HCV numbers are so high. The cure rate overall

was 54.2 percent with genotype 1 and 75 percent of those who had genotypes 2 or 3 (“New

Opportunities for the Management and Therapy of Hepatitis C in Correctional Settings.”).

Maintenance therapy is when peginterferon is used at a low dose indefinitely. It controls

the viral level which will reduce inflammation and stop the progression of fibrosis (Fabry and

Narasimhan, 2007, p. 78). In this way, in the minds of the doctor, HCV is no longer thought of

as a disease but more as a chronic illness. Patients who should consider this option are those

with “advanced fibrosis or compensated cirrhosis” (Fabry and Narasimhan, 2007, p. 79).

Prevention

“Hepatitis C is spread through blood-to-blood contact” (Fabry and Narasimhan, 2007, p.

17). Those with HCV must be extremely careful not to spread it

to anyone else and those without HCV must be careful not to

come into contact with another person’s blood if it is exposed.

A major way not to transmit hepatitis C is to not engage in any

drug activity whatsoever. Drugs are naturally contaminated with

a number of chemicals and poisons. Drug dealers are not known

for being very careful; therefore, anything could be in the drug being purchased, including HCV.

If an HCV patient has a drug problem, it’s

best to enroll in a substance abuse program so

that they may receive help in order to stop

using drugs.

15

Though it’s rare to transmit HCV through sexual activity, it is in the patient’s best

interests to inform their partner of any infections that they have; it is also recommended to use a

“new latex condom with lubricants to reduce the risk of bleeding” (Fabry and Narasimhan, 2007,

p. 18).

Other preventative precautions: “do not donate sperm, ova, or blood; clean blood spills

appropriately; do not share razor blades, toothbrushes, nail clippers, etc; dispose of feminine

hygiene products in plastic bags” (Fabry and Narasimhan, 2007, p. 19). Another way to prevent

HCV transfer is to not become pregnant while viral levels in the blood are high.

In summary, hepatitis C mainly attacks the liver. HCV was not identified until 1989 and

from then on, special screenings have been done on donated blood in order to reduce the risk of

transmission. It is transmitted through blood-to-blood contact. The most common way of HCV

transmission is intravenous or intranasal drug use. Most patients with this disease don’t show

any symptoms for years after receiving

the virus. RNA tests and a liver biopsy

are the best ways to test for the disease

and see how much damage it has been

done. Treatment includes different kinds

of therapy. The prognosis for HCV

patients is that they will either be cured,

have a relapse, or have to take a low dose of interferon for the rest of their lives. Preventing

transmission of the virus to yourself or anyone else is important and must be taken seriously to

16

Figure 1 Scientists are working on a vaccination.

refrain from infecting others. Unfortunately, no vaccine for hepatitis C is available at this time,

however, scientists are still working on this current problem.

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