Hepatitis

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Hepatitis
What Is Hepatitis?

The liver is the largest organ in the body, occupying the entire upper right
quadrant of the abdomen. It performs over 500 vital functions. It
processes all of the nutrients the body requires, including proteins,
glucose, vitamins, and fats. The liver manufactures bile, the greenish fluid
stored in the gall bladder that helps digest fats. One of the liver's major
contributions to life is to render harmless potentially toxic substances,
including alcohol, ammonia, nicotine, drugs, and harmful by-products of
digestion. Old red blood cells are removed from the blood by the liver and
spleen, and the iron is cycled to the bone marrow to make new ones.
Damage to the liver can impair these and many other processes. Hepatitis
is a disorder in which viruses or other mechanisms produce inflammation
in liver cells, resulting in their injury or destruction. In most cases this
inflammatory process is triggered when the immune system fights off
infections caused by viruses. It can also be caused, however, by an
overactive immune system that attacks its own liver cells. Inflammation of
the liver can also occur from medical problems, drugs, alcoholism,
chemicals, and environmental toxins. Hepatitis varies in severity from a
self-limited condition with total recovery to a life-threatening or life-long
disease.

Experts define hepatitis as short-term (acute hepatitis) or prolonged
(chronic hepatitis). In some cases, acute hepatitis develops into a chronic
condition, but chronic hepatitis can also occur on its own. Although
chronic hepatitis is generally the more serious condition, patients having
either condition can experience varying degrees of severity.

Acute Hepatitis

Acute hepatitis can begin suddenly or gradually, but it has a limited
course and rarely lasts beyond one or two months. Usually there are only
spotty liver cell damage and evidence of immune system activity, but on
rare occasions, acute hepatitis can cause severe -- even life-threatening --
liver damage.

Chronic Hepatitis

The chronic forms of hepatitis persist for prolonged periods. Experts
usually categorize chronic hepatitis as either (1) chronic persistent or (2)
chronic active hepatitis.

Chronic Persistent Hepatitis

Chronic persistent hepatitis is usually mild and nonprogressive or slowly
progressive, causing limited damage to the liver. Cell injury in such cases
is usually limited to the region of portal tracts, which contains vessels
that carry blood to the liver from the digestive tract. In some cases,
however, more extensive liver damage can occur over long periods of
time and progress to chronic active hepatitis.

Chronic Active Hepatitis

If damage to the liver is extensive and cell injury occurs beyond the portal
tract, chronic active hepatitis can develop. Significant liver damage has
usually occurred by this time. Liver cells are destroyed between the
portal tract and the central veins in the liver, and progressive cell damage
can build a layer of scar tissue over the liver, resulting in the condition
known as cirrhosis. In such cases, the entire liver is threatened with
malfunction and failure.

What Causes Hepatitis?

Viral Causes of Hepatitis

Most cases of hepatitis are caused by viruses that attack the liver; most
are named with the letters A through G. It should be noted that the cause
of hepatitis is sometimes unexplained, indicating that additional viruses
have not yet been discovered.

Hepatitis A

Hepatitis A, formerly called infectious hepatitis, is always acute and never
becomes chronic. The virus is excreted in feces and transmitted in
contaminated food and water. Eating shellfish taken from
sewage-contaminated water is a common means of contracting hepatitis
A. It can also be acquired by close contact with individuals infected with
the virus. The hepatitis A virus does not directly kill liver cells, and
experts do not yet know how the virus actually injures the liver.

Hepatitis B and D

The virus for hepatitis B, formerly called serum hepatitis, is found in
semen, blood, and saliva. It is usually spread by blood transfusions,
contaminated needles, and sexual contact. Blood screening as reduced
the risk from transfusions. The virus does not kill cells directly, but seems
to activate cells in the immune system, which cause inflammation and
damage in the liver. Hepatitis D virus can replicate only by attaching to
hepatitis B and therefore cannot exist without the B virus being present.
Between 1% and 10% of hepatitis B patients go on to develop chronic
hepatitis and hepatitis B can become chronic without an acute stage.

Hepatitis C

Hepatitis C was the major cause of all cases of hepatitis resulting from
transfusions and most resulting from intravenous drug use. Because of
blood screening, the risk from transfusions is now 1 in 10,000. It can also
be transmitted through injuries in the skin. It may also be transmitted
sexually. About 10% to 60% of acute hepatitis C patients develop the
chronic form, which can also occur without a preceding acute stage.

Hepatitis E

Hepatitis E is similar to hepatitis A and is transmitted by contact with
contaminated food or water. It was thought to be rare, but experts now
estimate that up to 20% of people in the US may be infected, even those
who haven't traveled.

Hepatitis G

Hepatitis G accounts for about 9% of cases that cannot be diagnosed as
hepatitis A through E. It also occurs in about 25% of patients with of
hepatitis A, 32% of those with hepatitis B, and 20% of patients with
hepatitis C. Hepatitis G appears always to be chronic, but to date
indications are that it is mild and does not even increase the severity of
any accompanying hepatitis virus.

Other Viruses Causing Hepatitis or Liver Damage

Hepatitis GB has been discovered as a new distinct form, but it is not
known yet whether it causes a serious condition. A number of other
common viruses, including herpes simplex, can sometimes injure the
liver, although they rarely cause severe hepatitis. Cytomegaloviruses are
harmless in most people but can injure the livers in infants and people
with impaired immune systems, such as those with AIDS.

Autoimmune Chronic Hepatitis

Chronic hepatitis may develop when the body's immune system attacks
cells in the liver, a condition called autoimmune chronic hepatitis.
Autoimmune chronic hepatitis accounts for about 20% of all chronic
hepatitis cases. Like other autoimmune disorders, this condition
develops because a genetically defective immune system attacks the
body's own cells and organs -- in this case, the liver -- after being
triggered by an environmental agent, probably a virus. This agent may be
a virus; suspects include the measles virus, a hepatitis virus, or the
Epstein-Barr virus, which causes mononucleosis. In about 30% of cases,
autoimmune hepatitis is associated with autoimmune disorders that
attack other parts of the body, but the relationship between these
conditions is unclear.

Hepatitis Caused by Alcohol and Drugs

Alcohol

Over time, alcohol abuse leads to increased demands for oxygen by the
liver and, at the same time, fat accumulates and impairs the liver's ability
to absorb oxygen. Cells in the liver become damaged and may die,
possibly leading to cirrhosis, a dangerous and life-threatening condition.

Drugs

Because the liver plays such a major role in metabolizing drugs,
hundreds of medications can cause reactions that are similar to those of
acute viral hepatitis. Symptoms can appear anywhere from two weeks to
six months after starting drug treatment. In most cases, they disappear
when the drug is withdrawn, but, in rare circumstances, they may
progress to serious liver disease. Among the drugs most prominently
cited for liver interactions are halothane, isoniazid, methyldopa,
phenytoin, valproic acid, and the sulfonamide drugs. Notably, very high
doses of acetaminophen (Tylenol) have been known to cause severe liver
damage and even death, particularly when used with alcohol.

Who Gets Hepatitis?

Risk Factors for Hepatitis A

About one third of the US population has antibodies to hepatitis A,
indicating previous infection by the virus. It infects 180,000 Americans
every year. Feces-contaminated water and food are the major sources of
infection, and infected people can transmit it to others if they do not take
strict sanitary precautions. Of the various strains of hepatitis, hepatitis A
is the one people are most likely to encounter in the course of
international travel. Outbreaks have occurred in day care centers, but a
recent study of child care workers found that incidence of hepatitis A and
B among this group was actually lower than in the general population.
Risk is low if good hygienic precautions are used, particularly when
changing babies and handling diapers. The disease has also been
transmitted sexually among homosexual men and it often occurs in
intravenous drug users.

Risk Factors for Hepatitis B and D

About 350 million people carry hepatitis B worldwide; it is very common
in southern Africa, Asia, and the Mediterranean. It is carried through body
fluids. In the U.S., there are about 128,000 new cases every year and
about 1 to 1.35 million people with chronic hepatitis B. It can infect
children and adults; up to 90% of hepatitis B patients are men. Blood
screening and vaccinations have significantly reduced the rate of
infection, but drug users who share needles are at considerable risk.
Hepatitis B may also be transmitted through sexual activity. Pregnant
women with hepatitis B can transmit the virus to their babies. Even if they
are not infected at birth, unvaccinated children of infected mothers run a
60% risk of developing it before age five. Children are more likely than
adults to become chronic carriers. The virus can be passed from cuts,
scrapes, and other breaks in the skin. Also at risk are hospital workers
exposed to blood products, staff members of institutions for mentally
impaired people, prisoners, and emigrants from areas where the disease
rate is high. Contaminated medical instruments, including fingerstick
devices used for more than one individual, have been known to transmit
the virus.

Hepatitis D occurs only in people with hepatitis B. It is not common in the
U.S. except in intravenous drug abusers and people who require multiple
transfusions. Those who have the antibody for hepatitis B are immune to
further infection from both hepatitis B and D viruses.

Risk Factors for Hepatitis C

About 28,000 people acquire hepatitis C every year and as many as 3.9
million Americans are chronic carriers of the virus. Its primary mode of
transmission has been through transfusions. Because of blood
screening this risk has been dramatically reduced to 1 in 10,000 since
1990. Hepatitis C can exist for decades, however, without symptoms, and
nearly 300,000 people who had transfusions before 1990 may have
contracted the virus. Experts urge anyone who had transfusions before
1990 be tested, even though treatments for the virus are limited. People
who are still at high risk for hepatitis C include intravenous drug users,
intranasal cocaine users, people who have had body-piercing, and organ
transplant recipients. Transmission of the virus through contaminated
medical devices used in invasive procedures, such as colonoscopy, has
been reported. Either sexual promiscuity or a long-term sexual
relationship with an infected partner appears to increase the risk. The risk
in long-term relationships is about 1% per year. The risk increases with
frequency of sexual activity and intimate behavior, such as sharing
toothbrushes. Although most health care providers are at low risk, the
chance of infection in hospital workers who are accidentally stuck with a
needle is high, ranging from 4% to 10%. Unless her own infection is
severe, a pregnant woman with this virus is unlikely to pass it on to her
infant. Even given these risk factors, it is still not known how 40% of
patients acquire this form of hepatitis.

Risk Factors for Hepatitis G

Hepatitis G is detected in between 1.5% and 3.2% of blood donors and is
believed to be more common than hepatitis C. From what is known of
hepatitis G, its risk factors are probably similar to those of hepatitis C,
although incidence among patients with multiple blood transfusions is
much lower than with hepatitis C.

Risk Factors for Autoimmune Chronic Hepatitis

Autoimmune chronic hepatitis may occur in women between the ages of
20 and 40 who have other diseases of the immune system, including
systemic lupus erythematosus, rheumatoid arthritis, Sjoulmgren's
syndrome, inflammatory bowel disease, glomerulonephritis, and
hemolytic anemia. About 30% of patients are men, however, and in both
genders there is often no relationship to another autoimmune disease. In
general, no major risk factors have been discovered for this condition.

What Are the Symptoms of Hepatitis?

Symptoms of Acute Viral Hepatitis

General Symptoms

Symptoms of acute viral hepatitis may begin suddenly or develop
gradually. They may be so mild that patients mistake the disease for the
flu. Nearly all patients experience some fatigue and often have mild fever.
Gastrointestinal problems are very common, including nausea and
vomiting and a general feeling of discomfort in the abdomen or sharper
pain that may be localized in the upper right quadrant. This pain tends to
increase during jerking movements, such as climbing stairs or riding on a
bumpy road. GI problems can lead to loss of appetite, weight loss, and
dehydration. After about two weeks, dark urine and jaundice -- a
yellowish color in the skin and whites of the eyes -- develops in some, but
not all, patients. Children tend not to develop jaundice. About half of all
hepatitis patients have light colored stools, muscle pain, drowsiness,
irritability, and itching -- usually mild. Diarrhea and joint aches occur in
about a quarter of patients. The liver may be tender and enlarged and
most people have mild anemia. In about 10% of patients, the spleen is
enlarged.

Symptoms of Fulminant Hepatitis

In very rare cases, within two months of onset, a very serious condition
known as fulminant hepatitis develops. Symptoms may include a large
swollen abdomen (known as ascites) and a peculiar hand-flapping tremor
(called asterixis). These symptoms may be followed by stomach and
intestinal bleeding and mental confusion, stupor, or coma caused by
brain injury (encephalopathy).

Symptoms Typical of Acute Hepatitis A

Symptoms of hepatitis A are usually mild, especially in children. They
generally appear between two and six weeks after exposure to the virus.
Adult patients are more likely to have fever, jaundice, and itching that can
last one to several months.

Symptoms Typical of Acute Hepatitis B

Hepatitis B symptoms appear long after the initial infection -- usually four
to 24 weeks. Many patients may not even experience symptoms, or they
may be mild and flu-like. About 10% to 20% of patients have a fever and
rash. Nausea is not common. Hepatitis B patients may experience
general aching in the joints, but sometimes the pain can resemble
arthritis, affecting specific joints and accompanied by redness and
swelling.

Symptoms Typical of Acute Hepatitis C

If they appear at all, symptoms develop about a month or two after a
person is infected with hepatitis C. These are usually milder than those of
hepatitis B. About 75% of patients show no signs of jaundice, and many
do not experience any symptoms.

Symptoms of Chronic Hepatitis

Symptoms of Chronic Hepatitis B and C. Both hepatitis B and C can
progress to chronic hepatitis usually with no early acute symptoms.
Symptoms of progressive chronic viral hepatitis may be very subtle and
no more than a mild persistence of acute symptoms for six or more
months. In fact, chronic hepatitis C can be present for as long as 20 years
without presenting any obvious problems. Some patients develop pain in
small joints in the body (such as the hand) that may be nearly
indistinguishable from symptoms of rheumatoid arthritis, fibromyalgia, or
carpal tunnel syndrome. In other patients, chronic hepatitis B or C can
lead to long term disability or liver failure before they experience any
symptoms at all.

Symptoms of Chronic Autoimmune Hepatitis

The symptoms of chronic autoimmune hepatitis range from minimal to
severe, including fatigue, jaundice, fever, and weight loss. The liver and
spleen are often enlarged. In addition, patients with this condition may
experience skin disorders, including palmar erythema (red palms) and
spider angioma (a blood-red spot, the size of a pin head, from which tiny
blood vessels radiate like spider legs). Itching is not common, however.
The abdomen or legs may be swollen due to the accumulation of fluid.

How Serious Is Hepatitis?

Prognosis for Acute Viral Hepatitis

In most cases of acute viral hepatitis, recovery is complete and the liver
returns to normal within two to eight weeks. In a small number of cases of
hepatitis B or C, the condition can be prolonged and recovery may not
occur for a year. About 5% to 10% of these patients will experience
flare-up of symptoms in a milder form before full recovery. A few of these
patients may go on to develop chronic hepatitis. In the rare event that
fulminant hepatitis develops, the liver fails and gastrointestinal
hemorrhage and brain damage (encephalopathy) occur, resulting in
mental confusion, or even coma. Without liver transplantation, death
occurs in up to 80% of these cases. Pregnant women with acute hepatitis
B, C, or E are at higher risk for these complications. Other serious, and
also rare, consequences of acute viral hepatitis are aplastic anemia
(which can be fatal), hypoglycemia, and polyarteritis -- a serious
inflammation of blood vessels. People who have been infected with a
hepatitis virus continue to produce antibodies to that specific virus. This
means that they cannot be reinfected with the same hepatitis virus again.
Unfortunately, they are not protected from other types.

Specific Prognosis for Hepatitis A and E

Hepatitis A is the least serious hepatitis virus; it never becomes chronic.
Fulminant hepatitis is the major concern, but even if this condition
develops, it is less dangerous than with other viral types; only one in a
thousand patients are at risk for death from this complication. Similarly
hepatitis E is acute and not serious, except in pregnant women, when it
can be life-threatening.

Specific Prognosis for Hepatitis B and D

Acute hepatitis B is lethal in only 1% of patients, but even patients with
mild symptoms can remain chronically infected with the virus. Between
5% and 15% of hepatitis B patients carry the virus throughout their lives,
and about 25% of these carriers progress to chronic hepatitis. People
most at risk for carrying the virus are children infected before they are
five and newborns, most of whom become carriers. People most at risk
for progression to chronic hepatitis are those infected in early childhood
and people with damaged immune systems, such as AIDS patients.

If a patient with hepatitis B becomes co-infected with hepatitis D, the
consequences can be very serious. There is an increased risk for
fulminant hepatitis, a life-threatening condition. The risk for developing a
chronic form of hepatitis D is the same as for hepatitis B alone.

Specific Prognosis for Acute Hepatitis C

The mortality rate for acute hepatitis C is well below 1%, but people
infected with hepatitis C tend to become life-long carriers of the virus.
Between 40% and 60% of these patients develop chronic hepatitis within
four years. It is currently not possible to predict which patients will
develop the chronic form of hepatitis C.

Prognosis for Chronic Hepatitis

Patients with chronic persistent hepatitis who have few, if any, symptoms
generally have a favorable outlook, with only a small risk for developing
cirrhosis. In chronic active hepatitis, however, liver biopsies often reveal
scarring indicative of cirrhosis and damage to the liver cells that bridge
the portal and central veins of the liver. Nearly every bodily process is
affected by a damaged liver, including digestive, hormonal, and
circulatory systems. Without treatment, encephalopathy, stomach and
intestinal bleeding, or kidney failure may eventually develop, with
life-threatening consequences. The degree of severity in people with
hepatitis caused by viruses B and C usually depends on the degree to
which the virus can replicate itself. Viruses that replicate quickly usually
cause a more severe form of chronic hepatitis.

Prognosis of Chronic Hepatitis B

The great majority of people with chronic persistent hepatitis B have a
good long-term outlook, but between 5% and 10% become carriers of the
virus and 5% to 10% eventually develop cirrhosis. The addition of
hepatitis D is a particular danger and increases the risk for cirrhosis.
Hepatitis B is a primary cause of liver cancer. In Asia about 15% of people
who have chronic hepatitis B develop liver cancer, but this high rate is
not seen in other parts of the world. (One Italian study which followed a
group of hepatitis B patients for 11 years found no development of liver
cancer over that period of time.) Vaccinations for hepatitis B is proving to
significantly reduce this risk.

Prognosis of Chronic Hepatitis C

A recent study reported that from the time of diagnosis, the 10-year risk
for the patients in the study developing cirrhosis was 29% and for liver
cancer was 14%. It should be noted that these patients had had hepatitis
for many years before being diagnosed, so these time frames are not
based on when a patient first gets hepatitis. One large study has
identified people at highest and lowest risk for developing cirrhosis:
people who contracted hepatitis after exposure in a hospital setting,
blood transfusion, and when the cause is unknown have a 20% to 30%
chance for cirrhosis; those who developed hepatitis C from drug abuse,
sexual activity, and occupational exposure have a lower risk -- around
10%. Another study found that drinking alcohol also significantly
increased the risk. A study reporting a high rate of hepatitis C in diabetics
has led some experts to theorize that the virus may have effects on the
immune system or pancreas that could cause this disorder in some
people.

Prognosis of Chronic Hepatitis G

Although only recently identified, experts believe that hepatitis G usually
has a mild chronic course and the likelihood of liver damage is low.

Prognosis for Autoimmune Hepatitis

The persistent form is usually benign and causes little trouble, although
there is a very small risk that chronic persistent hepatitis can evolve to
the active form. A recent study found that the overall outlook for treated
patients with autoimmune hepatitis and no indication of hepatitis viruses
was very favorable. In this study, the 10-year survival rate was 95% --
similar to the same age-group in the general population. The five-year
survival rate for chronic active form of this hepatitis is only 50% if the
disease is not treated. (This rate may be higher in people with milder
symptoms and less liver damage.) During the early years, patients are
most at risk for liver failure and bleeding in the stomach and esophagus.
This risk diminishes over time but is replaced by an increase in liver
cancer rates and bleeding in the stomach and intestines. The risk for liver
cancer is not has high, however, as with chronic viral hepatitis.

How Is Hepatitis Diagnosed?

Tests to Diagnose the Presence of Hepatitis

In people suspected of having or carrying viral hepatitis, physicians will
measure certain substances in the blood. One of the most important
factors indicative of hepatitis is bilirubin, a red-yellow pigment that is
normally metabolized in the liver and then excreted in the urine. In
patients with hepatitis, the liver cannot process bilirubin, and blood levels
of this substance rise, sometimes causing jaundice. Physicians will also
look for elevated blood levels of enzymes known as aminotransferases,
which are released when the liver is damaged. Aminotransferase levels
tend to rise before jaundice develops and to drop after it occurs. High
levels do not necessarily mean the condition is very severe, but levels
below 500 IU/L generally indicate mild disease.

Tests to Determine Causes of Hepatitis

To identify the particular virus causing hepatitis, blood tests called
radioimmunoassays are performed. Some of these tests can pin-point
hepatitis antigens, which are proteins that are unique to the specific
viruses. More commonly, radioimmunoassays identify particular
antibodies, which are molecules in the immune system that attack
specific antigens. Antibodies may not appear for up to weeks or months
after hepatitis develops, so if the tests are performed too early, they may
not detect antibodies even if the patient is infected. Antibodies also
persist after patients recover, so a positive antibody test can indicate a
previous infection but cannot necessarily determine if the infection is
active.

Tests for Hepatitis A

The first antibodies produced to fight the hepatitis A virus are IgM
antibodies. They appear early in the course of the disease and usually
can be identified using radioimmunoassays as soon as symptoms
appear. IgM antibodies disappear during recovery, but IgG antibodies
persist, indicating previous infection.

Tests for Hepatitis B and D

A radioimmunoassay for hepatitis B must be done promptly to identify
the antigen, HBsAg, which is found in the blood in early stages but
disappears within four months unless the patient becomes a long-term
carrier. Antibodies to the antigen appear during convalescence and may
be identified then, even if the antigen itself was missed early on. To
diagnose hepatitis D using an antibody test, hepatitis B must also have
been identified.

Test for Hepatitis C and G

A number of tests, particularly one known as enzyme-linked
immunosorbent assay (ELISA), are available for identifying the antibody
to the hepatitis C virus. The antibody for hepatitis C may not show up for
three to six months after the onset of the disease, so the absence of the
antibody is not necessarily an indication of a healthy liver. If the physician
still firmly believes the virus is present, another test, polymerase chain
reaction (PCR), may be performed. A PCR is able to make multiple copies
of the genetic material (the RNA) of the virus to the point where it is
detectable. It is also the only test available to identify hepatitis G but is
very expensive (about $200) and not recommended for what seems to be,
so far, a mild disorder.

Tests for Chronic Hepatitis

Blood tests for chronic hepatitis include measurements of
aminotransferase levels, bilirubin levels, and detection of blood clotting
problems. Immunoassays to detect antibodies to hepatitis viruses are
also performed. If a patient experiences symptoms of chronic active
hepatitis for six months or more and a virus cannot be identified, then
autoimmune hepatitis is usually suspected. To help confirm this
condition, test results may show high levels of immune factors called
serum globulins or certain antibodies to liver proteins. In some cases, a
successful trial of steroid drugs may be the only way to diagnose
autoimmune hepatitis. A liver biopsy may be performed for acute viral
hepatitis caught in a late stage or for severe cases of chronic hepatitis.
Some experts are now recommending biopsies for all chronic hepatitis C
patients, regardless of severity, because of the risk for liver damage even
in patients without symptoms. A biopsy helps determine treatment
possibilities, the extent of damage, and the long-term outlook.

How Is Acute Hepatitis Treated?

Treatment for Acute Viral Hepatitis

For mild cases of acute viral hepatitis, no drug therapy or other treatment
is either available or necessary. Hospitalization is needed only for people
at high risk for complications, such as pregnant women, elderly people,
patients with other serious conditions, or those who have severe nausea
and vomiting and need to have fluids administered intravenously. The
primary goals for managing acute viral hepatitis are to provide adequate
nutrition, to prevent additional damage to the liver, and to prevent
transmission to others.

No vitamins or special diets have been proven to be particularly
beneficial. Eating many small snacks during the day, with larger ones in
the morning, may help prevent weight loss while reducing the severity of
nausea. Patients might be able to tolerate high-caloric drinks to
supplement the regular diet.

The liver processes many types of medications, so as soon as hepatitis is
diagnosed, the patient should stop taking all drugs, including
over-the-counter medications, except those a physician specifically
prescribes or recommends. In some cases, the physician may prescribe
drugs that have minimal impact on the liver to alleviate the symptoms of
hepatitis, such as nausea or severe itching. All patients should abstain
from alcohol and sexual contact during the acute phase. Moderate
drinking (one or two drinks per evening) after recovery is not harmful for
most people. Everyone, however, should avoid taking acetaminophen
(Tylenol) with alcohol, which carries a risk for liver damage, even in
people without hepatitis.

Although most patients with hepatitis experience fatigue and require
more rest than usual, they can be as physically active as they want
without affecting recovery. In fact, patients should be encouraged to be
as active as they can. Depression is common, particularly in people used
to an active life. Patients should be reassured that in the great a majority
of hepatitis cases, recovery is complete.

At the onset of acute hepatitis, periodic visits to the physician for repeat
blood tests are necessary, the frequency of which depends on how well
the patient feels. If symptoms still occur after three months and laboratory
tests still indicate active presence of the virus, the patient should be
evaluated every month. If symptoms persist beyond 6 months, a liver
biopsy may be required to determine any liver damage.

Treatment for Fulminant Acute Hepatitis

For those who develop fulminant hepatitis and liver failure, treatment is
aimed at the affected organs and systems. No medications, including
corticosteroids, has any effect against the condition itself. Liver
transplantation is currently the only life-saving treatment for fulminant
acute hepatitis and has survival rates of up to 60%. Without liver
transplantation, the chance of survival is only 20%.

How Is Chronic Hepatitis Treated?

The goals for treating all forms of chronic hepatitis are to relieve
symptoms, prevent the development of cirrhosis, reduce viral levels, and
improve survival. The medical therapy of chronic viral hepatitis is very
different from the treatment of chronic autoimmune hepatitis, so a correct
diagnosis is essential.

Anti-Inflammatory Drugs and Treatment of Chronic Autoimmune Hepatitis

Patients with autoimmune hepatitis who have mild symptoms and slight
inflammation of the liver do not require any treatment except to alleviate
symptoms. They should be monitored, however, for any signs of disease
progression. Severe autoimmune hepatitis is a life-threatening condition
and requires intensive therapy. Because this hepatitis is caused by an
overactive immune system attacking the body's own cells, it is most
successfully treated with the steroid drugs prednisone and prednisolone.
Steroids suppress the immune system and reduce inflammation,
producing remission of symptoms in about 80% of patients. Azathioprine
(Imuran) is often prescribed along with steroids to help reduce severe
side effects caused by using steroids alone. Azathioprine also
suppresses the immune system and helps prevent relapse, but the drug
will not induce remission by itself. About half of patients relapse within
six months, and only about 20% of patients achieve remission (are
disease-free) for more than five years. Readministering prednisone
therapy after relapse achieves another remission in 80% of patients. In
one promising study, patients who continued to use azathioprine after
prednisolone was withdrawn had no relapses for at least a year.
Unfortunately, long-term use of azathioprine may increase the risk for
cancer, although studies indicate that this risk is very low.

For most patients, steroids reduce symptoms within three months,
improve liver function within six months, and restore liver health within
two years. Between 10% and 20% of patients continue to deteriorate
despite steroid treatment, although higher doses may help some of these
people. Treatment usually needs to continue about two years before the
disease is in complete remission, but it rarely lasts more than three years.
Side effects can be very distressing and sometimes serious; they include
weight gain, skin problems, moon-shaped face, high blood pressure,
diabetes, cataracts, mental disturbances, infections, and osteoporosis.
Usually, steroids are stopped when disease symptoms have
disappeared, when blood tests show that aminotransferase levels are
less than two times normal, and liver biopsies reveal no active cell
damage. Steroid medications must be withdrawn very slowly. Patients
who are very elderly or who have advanced cirrhosis are not good
candidates for this treatment. It should also be noted that about 85% of
people with chronic active autoimmune hepatitis do not have severe
symptoms; in these cases, physicians often must weigh the risk for
progression to a more serious condition against the long-term adverse
effects of steroid treatment. If all therapies fail and the disease becomes
life-threatening, liver transplantation may be performed. Because of all of
these effective treatment options and in spite the high rate of relapse,
long-term survival rates in patients with autoimmune hepatitis are
excellent. (Steroids are generally not useful for chronic hepatitis B or C
and, in fact, suppressing the immune system in these patients can
encourage the viruses to replicate more quickly.)

Drug Treatment for Chronic Hepatitis B, D, or C

Drug treatments for chronic hepatitis B, D and C are aimed at reducing or
preventing liver damage and boosting or modifying the immune system
to promote its attack on the viruses. Treatment outcomes are assessed
by testing levels of aminotransferase to determine liver damage and
using polymerase chain reaction (PCR) tests to detect the amount of
virus left. After treatment, however, some patients may have low levels of
virus and high indicators of liver damage while others display opposite
results. It is not yet clear how to weigh these criteria in evaluating the
overall health of the patient.

Interferons

Interferons act directly against the virus. The standard drug currently
used for chronic viral hepatitis B, D, and C is interferon alpha-2b
(Roferon-A, Intron A). Other interferons are being tested, including
recombinant type-I interferon (Infergen) and interferon beta, which is
benefiting many children with hepatitis B who do not respond to
interferon-alpha. In those who respond to interferon, studies are showing
improved symptoms, a normal long-term survival rate, and, in some, no
return of the disease. The percentage of patients who benefit over the
long-term, however, is small. Not all patients are candidates; among
others, the treatment is inappropriate for patients with advanced
hepatitis, fluid in the abdomen, or any serious medical or psychiatric
problems. Even when the drug is effective, the disease recurs half the
time and requires additional treatment.

Patients with hepatitis B should be given interferon if they show signs of
liver damage; it is not recommended for those with normal
aminotransferase levels. The drug has eliminated the virus and sustained
significant remission in 25% to 40% of patients with chronic hepatitis B.
The drug is usually taken by injection every day for 16 weeks.

In patients with hepatitis C taking interferon for six months there is an
even lower average rate of sustained response -- about 15%. (Although
studies indicate this rate can be boosted to 24% with treatment of a year
or longer.) Early eradication of the virus is the most important factor for
success In one study, over 75% of patients whose viral count was
eliminated in the first week had a sustained response. However, only 35%
of those whose count was down by week two and 12.5% of those whose
count was down by the fourth week had a sustained response. In some
cases, a very short course of corticosteroids may be used initially to
boost the effect of interferon. (In such cases, the steroids do no harm.)
Effects of the drug may be enhanced before treatment in certain patients
by reducing iron levels through a series of blood-drawings.
Combinations with other drugs, including ribavirin, thymosin alpha, or
ursodeoxycholic acid, are showing promise (for more information on
these drugs, see discussions below).

Common side effects are flu-like symptoms that usually occur within six
hours and last for 12. More chronic effects include depression, irritability,
weight loss, vomiting, and general weakness. Interferon often causes a
drop in platelet and white blood cell counts, increasing susceptibility to
bacterial infections. It may also trigger an autoimmune response,
possibly causing anemia, diabetes, lupus-like symptoms, thyroid
abnormalities, or even autoimmune hepatitis.

Nucleoside Analogues

Among the drugs showing promise for patients who do not respond to
interferon are nucleoside analogues, which directly affect viral
replication. Such drugs include ribavirin, lamivudine (Epivir), famciclovir
(Famvir), and adefovir. Lamivudine has reduced hepatitis B to
undetectable levels after four weeks. Unfortunately, the virus recurs in
almost all cases, although this recurring mutation may be weaker than
the original strain. Administering the drug for longer periods may
produce sustained remission in more patients while still being safe. A
study using adefovir, also called GS840, reported a drop in hepatitis B
virus levels of 97% in 20 patients. For hepatitis C patients, the most
promising treatment is a combination of ribavirin and interferon alpha
(Rebetol), which has produced sustained improvement in 40% to 77% of
hepatitis C patients. This treatment may not be effective, however, in
people with severe or late-stage disease.

Other Drugs that Stimulate the Immune System

Immunomodulators are drugs that modify or regulate part of the immune
system. One of these, thymosin is a synthetic version of a peptide derived
from the thymus gland and is a promising therapy when used alone or in
combination with interferon for hepatitis B or when used in combination
with interferon for hepatitis C. Vaccines, including Hepagene, are being
investigated for treating and preventing hepatitis B.

Other Investigative Drugs

Amantadine (Symmetrel) is a drug commonly used for Parkinson's
disease but which may have some antiviral effects. In hepatitis C patients
who had failed interferon, the drug produced normal aminotransferase
levels in 27% and it reduced the viral load to undetectable levels while
producing a sustained response in 18% of these patients. Ursodiol, or
ursodeoxycholic acid, a drug ordinarily used for gallstones, improves
aminotransferase levels, although it has no effect against the virus. For
hepatitis C patients it may prove useful in combination with interferon but
it is not useful alone.

Liver Transplantation

If treatment fails for any type of severe hepatitis, liver transplantation may
be tried, although hepatitis B patients have a success rate of only 50% to
60% because of recurrence. (The success rate is higher in those who
have hepatitis D.) Experiments using monthly infusions of hepatitis B
immune globulin (HBIg) after transplantation show great promise in
preventing recurrence in these patients. This may need to be
administered life long. One study reported that lamivudine may be helpful
in preventing recurrence of hepatitis B after liver transplantation.
Hepatitis C also commonly returns in transplanted livers, progressing to
cirrhosis within an average of 51 months in 8% of patients. Autoimmune
hepatitis may also recur after liver transplantation, but only after several
years. Unfortunately, there are only about half the number of available
livers as there are candidates. New regulations controlling liver
transplantation now give priority to patients with the best chance of
long-term survival -- such as a young person with severe mushroom
poisoning as opposed to an elderly person with alcoholic cirrhosis.

How Is Transmission of Hepatitis Prevented?

Periods of Highest Contagion

Hepatitis A is infectious for two to four weeks before symptoms develop
and for a few days afterward. People with hepatitis B or C may become
carriers of the virus after recovery, even if chronic disease does not
develop and symptoms are not present.

Life-Style Preventive Measures

Daily Precautions

Patients with viral hepatitis should abstain from sexual activity or take
strict precautions if they cannot. Sterilizing utensils or clothing is not
necessary with any type of hepatitis, but hot water and thorough
cleanings are necessary for items used by patients with hepatitis E and A.
Utensils used by the patient for eating and cooking should be kept
separate from those used by others. Because hepatitis A and E are
usually passed through contaminated food, people with these viruses
should not prepare food for others; unfortunately these viruses are most
contagious before symptoms appear. Restrictions on food preparation
are not necessary for other types of hepatitis. All objects contaminated by
blood from patients with hepatitis B or C must be handled with special
care.

Travel to Countries at High Risk for Hepatitis

Travelers should be vaccinated against hepatitis A if they are traveling for
long periods of time to countries where epidemics occur. They should
peel and wash all fresh fruits and vegetables themselves and avoid raw
or undercooked meat and fish. Even ice cubes can cause infection, and
only carbonated bottled water should be used for brushing teeth and
drinking. If carbonated water is not available, tap water should be boiled
for ten minutes.

Vaccinations and Preventive Measures for Specific Viruses

Prevention of Hepatitis A

The standard preventive measure against hepatitis A has been immune
globulin (formerly gamma globulin) injections. A vaccine, Havrix, is now
available and is very safe and effective. It can be given along with immune
globulin and other vaccines. Although not yet routinely given to children
under two, the vaccine is proving to be safe for infants. People who
should receive Havrix include those in communities where outbreaks
occur, sexually active homosexual men, people with chronic liver
disease, health care workers exposed to the virus, and travelers to
developing countries. Travelers should also receive immune globulin if
they are visiting high risk areas within four weeks of the vaccination.
There are few side effects although allergic responses can occur. Hair
loss has been reported in a very few people after a second
administration.

Prevention of Hepatitis B and D

All transfused blood is now tested for both hepatitis B and C, significantly
reducing the risk from this source. Several vaccines, including
Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent
hepatitis B and are effective and safe, including for infants and children.
Vaccination programs are also proving to reduce the risk for liver cancer.
Because the incidence of hepatitis B is rising in the U.S., experts
recommend immunization against hepatitis B in all infants and children
older than eleven and those under eleven who live in areas populated by
immigrants from countries with a high incidence of the disease. Others
who should be vaccinated are people who have had sexual contact with
infected individuals, health care workers who may come in contact with
contaminated blood or body fluids, and people who travel frequently or
stay for prolonged periods in countries with high prevalence of this
disease. Three doses given over six months are usually required for
adults; a recent study reported that older adults would benefit from a
fourth dose without incurring serious side effects. People with
alcoholism, who often have a lower response, may be protected with high
doses. A small percentage of people do not develop immunity even after
a vaccine has been given repeatedly. A more potent vaccine is proving to
be effective in many people who do not respond to a standard vaccine.
The vaccine loses its effect after five years in about a third of those who
had it, but the value of a booster shot is uncertain. Preventing hepatitis B
also prevents hepatitis D. Screening pregnant women for hepatitis B and
then treating the infants of infected mothers as soon as they are born
appear to be very effective prevention strategies for newborns. Treatment
is with immune globulin and a series of vaccinations at birth, one month,
and six months.

Prevention of Hepatitis C

Although transfused blood has been tested for both hepatitis B and C
since 1990, those with previous transfusions -- even those performed
decades ago -- may be at risk. Such individuals are urged to be tested.
Immune globulin helps protect against developing hepatitis C after
transfusions. Periodic doses of immune globulin in sexual partners of
infected people also appear to confer protection. Avoiding exposure or
preventing transmission is, however, still very important for hepatitis
carriers and for those in contact with them. Infected patients should use
condoms and contraceptives that prevent passage of the virus, possibly
even in relationships that last for years. Sexual partners, no matter what
the duration of the relationship, should avoid sharing personal items,
such as razors or toothbrushes, and abstain from sexual activity during
menstruation or infections that cause bleeding in the genital or urinary
areas. Community needle exchange programs should be encouraged.
Studies are finding that these programs reduce the incidence of both
hepatitis and AIDS significantly without encouraging drug abuse.

(Recent Literature

Acute non-A-E hepatitis in the United States and the role of hepatitis G
virus infection. The New England Journal of Medicine, 3/13/97.)



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