| * Please note that most treatment modalities listed below are based on conventional medicine. PreventDisease.com does not advocate the use of any pharmaceutical drug treatments. Long-term drug therapy is very detrimental to human health. All drug information is for your reference only and readers are strongly encouraged to research healthier alternatives to any drug therapies listed.
a disorder in which viruses or other mechanisms produce inflammation
in liver cells, resulting in their injury or destruction. [ See
Box The Liver.] 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
Experts define hepatitis in one of two ways:
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.
is the largest organ in the body, occupying the entire upper
right quadrant of the abdomen. It performs over 500 vital
functions. Among them are the following:
to the liver can impair these and many other processes.
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
Old red blood cells are removed from the blood by the
liver and spleen, and the iron contained in them is
recycled to the bone marrow to make new red blood cells.
can begin suddenly or gradually, but it has a limited course and
rarely lasts beyond one or two months. Usually there is only spotty
liver cell damage and evidence of immune system activity, but on
rare occasions, acute hepatitis can cause severe, even life-threatening,
The chronic forms
of hepatitis persist for prolonged periods. Experts usually categorize
chronic hepatitis as either (1) chronic persistent or (2) chronic
active hepatitis, which are indications of severity. Chronic persistent
hepatitis is usually mild and nonprogressive or slowly progressive,
causing limited damage to the liver. If damage to the liver is extensive
and cell injury occurs beyond the portal tract, chronic active hepatitis
can develop. [ See How Serious is Hepatitis, below.]
of Viral Hepatitis
Most cases of
hepatitis are caused by viruses that infect liver cells and begin
replicating. They are defined by the letters A through G. [For details
of common specific hepatitis viruses, see Table Specific
Hepatitis Viruses: Modes of Transmission.] Investigators are
still looking for additional viruses that may be implicated in hepatitis
unexplained by the current known viruses. For example, hepatitis
GB (not discussed in the table) has been discovered as a new distinct
hepatitis virus. Another recently detected virus called transfusion-transmitted
virus (TTV) may be more common than previously thought and may be
transmitted via means in addition to transfusions. It is not yet
known whether either of these viruses injure the liver. A number
of other common viruses, including herpes simplex, can sometimes
injure the liver, although they rarely cause severe hepatitis.
Scientists don't know exactly how specific hepatitis viruses injure
the liver. As the virus reproduces in the liver, a number of proteins
and enzymes, including many that attach to the surface of the viral
protein are also produced. Some of these may be directly responsible
for liver damage. Researchers are investigating elevated levels
of specific T-cell sub-types in the liver of hepatitis C and B patients.
T-cells are important infection fighters in the immune system. Some
evidence suggests, however, that the specific T-cells found in hepatitis
B and C can release powerful inflammatory agents (eg, tumor necrosis
factor and interferon gamma) that can cause considerable damage.
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. Suspects include the measles
virus, a hepatitis virus, or the Epstein-Barr virus, which causes
mononucleosis. It is also possible that a reaction to a drug or
other toxin that affects the liver also triggers an autoimmune response
in susceptible individuals. In about 30% of cases, autoimmune hepatitis
is associated with other disorders that involve autoimmune attacks
on other parts of the body.
Caused by Alcohol and Drugs
About 10% to 35% of heavy drinkers develop alcoholic hepatitis.
In the body, alcohol breaks down into various chemicals, some of
which are very toxic in the liver. After years of drinking, liver
damage can be very severe, leading to cirrhosis in about 10% to
20% of cases.
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
Nonalcoholic steatohepatitis (NASH) has features similar to alcohol-induced
hepatitis, particularly a fatty liver, but it occurs in individuals
who do not consume significant amounts of alcohol. This disorder
may occur in conjunction with obesity, diabetes, high cholesterol
levels, small intestine surgery, or other factors. Research now
suggests that insulin resistance plays a role in the development
of NASH. Insulin resistance is the major problem in type 2 diabetes,
in which the body resists the action of insulin, which causes an
increase in blood sugar.
NASH should be considered as a possible cause of chronic hepatitis
when other acquired causes have been eliminated. Weight reduction
and management of any accompanying medical condition are the primary
approaches to nonalcoholic steatohepatitis. To date, however, there
is no effective treatment for NASH, although experimental therapies,
such as bile acids, antibiotics, nutritional supplements, and antioxidants,
have had some success in selected patients.
Factors for Hepatitis A
About one third
of the US population has antibodies to hepatitis A, indicating previous
infection by the virus. The hepatitis A virus infects up to 200,000
Americans every year and causes symptoms in about 134,000 of them.
Almost 30% are children under age 15.
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. Among the people at risk for passing
the infection along or being infected are the following:
travelers. Hepatitis A is the hepatitis strain people are most
likely to encounter in the course of international travel. In
fact, in spite of the availability of a vaccine, the increase
in travel to underdeveloped countries has kept the incidence
of hepatitis A steady in Western nations. The incidence may
even be increasing.
- Day care
employees and children. It is estimated that between 11% and
16% of hepatitis A cases occur among day care employees and
children who attend day care. The risk for children attending
day care is very low, however, if hygienic precautions are used,
particularly when changing babies and handling diapers.
active homosexual men.
- Food industry
Factors for Hepatitis B and D
for Hepatitis B. Worldwide, about 350 million people carry
hepatitis B (HBV). Three quarters of chronic hepatitis B carriers
live in the Asia Pacific region. It is also common in southern Africa
and the Mediterranean regions. In the US, there are up to about
320,000 new cases every year, with up to 160,000 experiencing symptoms.
Despite blood screening and vaccinations in children the current
annual incidence is holding steady. This may indicate that sexual
activity is an important route for viral transmission and that the
protective effect of the vaccine has not yet reached older, high-risk
groups. Also, as with hepatitis A, the increase in travelers to
underdeveloped nations may also be responsible for the steady rate.
Up to 90% of HBV patients are men, although it can infect children.
The following are some people at risk:
for Hepatitis D. Hepatitis D occurs only in people with hepatitis
B. It is not common in the US and the incidence of this hepatitis
is declining rapidly overseas. Experts anticipate that it will be
extremely rare in the near future. Those who recover from hepatitis
B are immune to further infection from both hepatitis B and D viruses.
- Drug users
who share needles are at considerable risk.
of infected mothers. Pregnant women with hepatitis B can transmit
the virus to their babies. Even if they are not infected at
birth, unvaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.) children of infected mothers run a 60% risk
of developing it before age five. Children are more likely than
adults to become chronic carriers, although between 6% and 12%
of children spontaneously recover each year.
workers and others exposed to blood products. Contaminated medical
instruments, including fingerstick devices used for more than
one individual, have been known to transmit the virus.
members of institutions for mentally impaired people.
from areas where the disease rate is high. (International travelers
who spend long periods in such areas may also be at risk.)
most at highest risk for becoming chronic carriers of the virus
are the following:
infected before they are five, including newborns, most of whom
people with damaged immune systems, such as AIDS patients.
Factors for Hepatitis C
There are about
36,000 new hepatitis C (HCV) infections every year in the US, which
is a significant decline compared to previous decades. During the
1980s, about 230,000 cases occurred each year. These high rates
have resulted in an estimated 2.7 million to 4 million cases of
chronic hepatitis C in America, and this condition also affects
170 million people worldwide.
African Americans are twice as likely as whites to be infected,
and men are at greater risk than women. It is currently not possible
to predict which patients will develop the chronic form of hepatitis
C. Some people at known risk for initial infection are as follows:
drug users. Intravenous drug use has been the greatest risk
factor for HCV since the early 1980s. It accounts for 60% of
new cases and 20% to 50% of chronic infections. Individuals
who engage in this activity have a risk for infection that is
between 50% and 80%. According to a 2001 study, even among young
people who have access to needle exchange programs, 45% are
infected with HCV at any time and 11% become infected each year.
Intravenous drug use, particularly in people who also drink
alcohol heavily, poses a higher risk for severe complications.
Intranasal cocaine use also appears to increase the risk.
who had transfusions before 1992. Although transfused blood
has been tested for both hepatitis B and C since the early nineties,
individuals given transfusions before then, even decades before,
may still be at risk. Such individuals are urged to be tested.
Hepatitis C can exist for decades without symptoms, and nearly
300,000 people who had transfusions before 1992, including many
who were children at the time, may have been infected. Of some
reassurance was a 1999 study of 458 people who had transfusions
when they were children. After an average of 20 years only 8%
tested positive for hepatitis C and only three people showed
signs of any liver abnormalities. These results suggest that
the virus may be less aggressive in children than adults, but
further observations are needed to learn if the infection remains
mild beyond age 30.
who survive cancer.
who have had body piercing or tattoos.
who have been either sexually promiscuous or people in a long-term
sexual and intimate relationship with an infected partner. (It
is not fully known, however, how sexual transmission occurs
in these cases. One study, for instance, found no genetic traces
of the virus in the semen of men infected with hepatitis C.)
workers and patients exposed to them. Most health care providers
are at low risk, although the chance of infection in hospital
workers who are accidentally stuck with a needle is high, ranging
from 4% to 10%. (It is not yet clear if this poses any significant
risk to patients. Some evidence suggests, for example, that
patients operated on by infected surgeons have a risk for HVC
that ranges from one in 1,750 to one in 16,000. Some experts
believe, however, that the risk for the patient is significantly
of infected mothers. Some experts believe that the transmission
of the hepatitis C virus from an infected mother to her infant
could become the major route of infection as preventive measures
against other modes of transmission become commonly applied.
At this time the risk to the infant from an infected mother
is between 5% to 30%, depending on a number of risk factors.
The highest rates of infection are in mothers who are also HIV
positive. Cesarean section delivery in infected mothers may
help protect the infants from contracting hepatitis C during
delivery, but it is not fool proof.
- The risk
factors for developing chronic hepatitis are not known.
Factors for 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 hepatitis A, 32%
of those with hepatitis B, and 20% of patients with hepatitis C.
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.
Factors for Autoimmune Chronic Hepatitis
hepatitis typically occurs in women between the ages of 20 and 40
who have other autoimmune diseases, including systemic lupus erythematosus,
rheumatoid arthritis, Sjögren's syndrome, inflammatory bowel
disease, glomerulonephritis, and hemolytic anemia. Some research
indicates that the postmenopausal period may be another peak in
incidence of AIH among women. 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.
Factors for Alcoholic Hepatitis
drinking itself is the major risk factor for alcoholic hepatitis,
genetic factors may play a role in increasing a person's risk for
alcoholic hepatitis. Women who abuse alcohol are at higher risk
for alcoholic hepatitis and cirrhosis than are men who drink heavily.
High fat diets may also increase the risk in heavy drinkers.
Factors for Nonalcoholic Steatohepatitis
plus hypertension are the major risk factors for nonalcoholic steatohepatitis.
The condition occurs in about 25% of severely obese people according
to a 2001 study.
SPECIFIC HEPATITIS VIRUSES: MODES OF TRANSMISSION
A. (formerly called infectious hepatitis)
Excreted in feces and transmitted by 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
B (HBV) and D. (formerly called serum hepatitis)
Transmitted through blood transfusions, contaminated needles,
and sexual contact. Blood screening has reduced the risk
from transfusions. Can be passed from cuts, scrapes, and
other breaks in the skin. Hepatitis D virus can replicate
only by attaching to hepatitis B and therefore cannot exist
without the B virus being present.
C (HCV). (formerly called non-A non-B hepatitis.)
Until blood screening began in 1990, the primary mode of
known transmission was through transfusions. Also transmitted
through contaminated needles. Possibly sexual transmission.
Cause of transmission now unknown in 40% of cases.
Contact with contaminated food or water.
Modes of transmission probably similar to hepatitis C although
risk is much lower.
ARE THE SYMPTOMS OF HEPATITIS?
of Acute Hepatitis
In general, the
symptoms of acute hepatitis are common to all viral strains but
they may differ somewhat. [ See Table Viral Hepatitis Types.]
Symptoms of acute viral hepatitis may begin suddenly or develop
gradually. They may be so mild that patients mistake the disease
for the flu. They include the following:
Fulminant Hepatitis. In very rare cases, within two months
of onset of acute hepatitis, a very serious condition known as fulminant
hepatitis develops. Symptoms may include the following:
all patients experience some fatigue and often have mild fever.
problems are very common, including nausea and vomiting and
a general feeling of discomfort in the abdomen or a sharper
pain that may occur in the upper right area if the abdomen.
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.
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.)
half of all hepatitis patients have light colored stools, muscle
pain, drowsiness, irritability, and itching, usually mild.
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.
- A large
swollen abdomen (known as ascites) and a peculiar hand-flapping
tremor (called asterixis).
symptoms may be followed by stomach and intestinal bleeding
and mental confusion, stupor, or coma caused by brain injury
of Chronic Hepatitis B and C
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 10 to 30 years without presenting any obvious problems.
In some patients, itchy skin may be the first symptom. Overall,
fatigue is the most common symptom affecting the quality of life
of patients with chronic hepatitis C. Symptoms of chronic hepatitis
can impair daily function, vitality, and mood in ways that are similar
to other chronic diseases. 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 some cases, however, cirrhosis or liver failure can
develop before patients experience any symptoms at all.
of Chronic Autoimmune Hepatitis
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 pinhead, 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
IS HEPATITIS DIAGNOSED?
Tests to Diagnose the Presence of Hepatitis and Its Severity
In people suspected
of having or carrying viral hepatitis, physicians will measure certain
substances in the blood.
Bilirubin is one of the most important factors indicative of
hepatitis. It is 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. (High levels of bilirubin cause the
yellowish skin tone, known as jaundice.)
Enzymes known as aminotransferases, particularly aspartate
(AST) and alanine (ALT) are released when the liver is damaged.
Measurements of these enzymes are important for detecting hepatitis,
determining its severity, and monitoring treatment effectiveness
in some cases.
to Determine Causes of Hepatitis
To identify the particular virus causing hepatitis, blood tests
called radioimmunoassays are performed. Typically, radioimmunoassays
identify particular antibodies, which are molecules in the immune
system that attack specific antigens. (Antigens are any molecules
that the body considers threatening or dangerous and which can be
targeted by antibodies.) Some of these tests can pinpoint hepatitis
antigens directly. These tests, however, have limitations:
The assays for
individual hepatitis viruses may differ. [See Table, Tests for Individual
may not be sufficient numbers of antibodies to be detectable
by blood tests for up to weeks or months after hepatitis develops.
Blood tests that are taken too early, then, may miss these signs
also persist after patients recover, so a positive antibody
test can indicate a previous infection but does not necessarily
determine if the infection is active.
Polymerase Chain Reaction. In some cases of hepatitis C,
a 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.
for Specific Hepatitis Viruses
Radioimmunoassays are generally used to identify IgM
antibodies, first produced to fight hepatitis A. They appear
early in the course of the disease and usually can be identified
as soon as symptoms appear. IgM antibodies disappear during
recovery, but those known as IgG antibodies persist,
and their presence can be used to indicate a previous infection.
B and D
A radioimmunoassay must be done promptly to identify the
antigen HBAg, 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.
An accurate home test (Hepatitis C Check) is now available
for identifying the antibody to the hepatitis C virus. Results
take about a week.
The standard test is known as enzyme-linked immunosorbent
assay (ELISA). The antibody for hepatitis C is used to identify
the virus but it may not show up for three to six months
after the onset of the disease, so its absence is not necessarily
an indication of a healthy liver.
A PCR for the RNA (the genetic material) of the virus may
be performed if the physician still firmly believes the
virus is present. Virus levels are also used to determine
treatment effectiveness. It is important to remember, however,
that viral levels are not an accurate measure of actual
liver damage. Only a biopsy can determine this.
Tests may also be used to determine the genotype of the
virus. Genotype 1, the most common, also requires more aggressive
treatments. Patients with genotypes 2 and 3 respond well
to treatment and, in some cases, may not need intensive
Autoimmune Chronic Hepatitis. 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. There
are other autoimmune liver diseases, however, that can confuse a
diagnosis. 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.
No laboratory tests for enzyme or viral levels can truly determine
the actual damage to the liver. Only a biopsy helps determine treatment
possibilities, the extent of damage, and the long-term outlook.
The biopsy requires abdominal surgery, most often laparoscopy. This
procedure requires general anesthesia and involves the following
A less invasive
procedure called a minilaparoscopy uses a smaller scope and may
prove to reduce the time of the procedure.
- The physician
makes one or more small incisions about half an inch to an inch
in the abdomen.
dioxide or nitrous oxide is delivered through the incision to
inflate the abdomen so that the involved area is visible.
- The surgeon
inserts a thin tube called a laparoscope that contains a tiny
camera. Surgical instruments are also inserted through the incision
to remove the liver tissue for biopsy.
- It takes
about an hour.
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 a 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), pancreatitis,
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.
Prognosis for Chronic Hepatitis
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. Nearly every bodily process is affected by a damaged liver,
including digestive, hormonal, and circulatory systems. Symptoms
can significantly impair daily life.
after infection from hepatitis viruses see Table Specific
Hepatitis Viruses: Severity and Outlook.]
If liver cells are destroyed between the portal tract and the
central veins in the liver, 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. If cirrhosis develops, the average
survival time is about 10 years. The risk for cirrhosis is much
higher in patients with hepatitis C than in those with hepatitis
B. [For more information, see the report
Cancer. The risk for liver cancer in patients with cirrhosis
is about 14%. (Liver cancer is rare in patients who do not
High Risk Chronic Hepatitis C Patients
Because there are millions of Americans now infected with
chronic hepatitis C, experts have been justifiably concerned
that there will be a significant number of cases of liver
failure and liver cancer in the coming years.
Having an aggressive genetic type of the virus (specifically
genotype 1) may be the strongest factor in predicting severity
in chronic hepatitis C, patients in the following categories
may also be at higher risk for developing severe liver damage
than other patients:
Being male may pose a higher risk for severity than
Developing hepatitis C at an older age.
Heavy alcohol users.
Co-infection with HIV or hepatitis B. Co-infection with
hepatitis C and B significantly affects the outcome
of these patients and may be more common than previously
believed. This co-condition may reduce these patients'
responses to interferon therapy and increase their risk
of liver cancer.
A history of transfusions. (One study reported that
they are twice as likely as intravenous drug users to
Being overweight, particularly if fat is distributed
in the abdomen (an apple-shape). This condition may
pose a higher risk for a fatty liver, which in turn
is more apt to become scarred and cirrhotic.
Having large iron stores in the liver.
SPECIFIC HEPATITIS VIRUSES: SEVERITY AND OUTLOOK
and Severity of Acute Symptoms.
(For General Description of Acute Hepatitis Symptoms,
see What Are the Symptoms of Hepatitis?)
for Becoming Chronic
A (formerly called infectious hepatitis). Does not directly
kill liver cells. Unclear how the virus actually injures
Symptoms are usually mild, especially in children. Generally
appear between two and six weeks after exposure to the virus.
Adult patients more likely to have fever, jaundice, and
itching that can last one to several months.
Least serious of the common hepatitis viruses. Never becomes
chronic. Fulminant hepatitis is the only major concern,
but even if it develops, it is almost always less dangerous
than with other viral types. Only one in a thousand patients
are at risk for death from this complication. If hepatitis
A infection occurs in patients with hepatitis C, however,
superinfection can occur, even without cirrhosis, leading
to a life-threatening form of fulminant hepatitis. (Infection
of patients with hepatitis B who do not have cirrhosis does
not appear to be as dangerous.)
B and D (formerly called serum hepatitis). The virus
does not kill cells directly, but seems to activate cells
in the immune system, which cause inflammation and damage
in the liver.
Symptoms appear long after the initial infection, usually
four to 24 weeks. Many patients may not even experience
them or they may be mild and flu-like. About 10% to 20%
of patients have a fever and rash. Nausea is not common.
Sometimes general aching in the joints. The pain can resemble
arthritis, affecting specific joints and accompanied by
redness and swelling.
Between 5% and 15% of hepatitis B patients carry the virus
throughout their lives, and about 25% of these carriers
progress to chronic hepatitis. Hepatitis B can become chronic
without an acute stage.
The risk for developing a chronic form of hepatitis D is
the same as for hepatitis B alone.
Form. Acute hepatitis B is lethal in 1% of patients,
but even patients with mild symptoms can remain chronically
infected with the virus. 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.
Chronic Form. Worldwide, approximately two million
people die each year from hepatitis B, globally making it
the ninth leading cause of death. Even so, the great majority
of people with hepatitis B have a good long-term outlook,
especially children infected with the virus. About 5% to
10% eventually develop cirrhosis. Co-infection with hepatitis
D or C increases the risk for cirrhosis. 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 that followed a group of hepatitis B
patients for 11 years found no development of liver cancer
over that period of time.)
If they appear at all, symptoms develop about a month or
two after a person is infected. 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.
Infected people tend to become life-long carriers.
50% to 91% of infected people develop chronic hepatitis.
At least 20 genetic variants have been identified. Even
if antibodies eliminate one strain, others can maintain
Form. Acute hepatitis C is rarely serious. In fact,
there are no symptoms in up to 80% of acute cases.
Chronic Form. About 15% of chronic hepatitis C patients
recover spontaneously, and about 25% have a mild and benign
course with normal liver enzymes. Even among those with
abnormal liver enzymes, most will have minimal liver damage.
Still chronic hepatitis is responsible for between 8,000
to 10,000 US deaths a year. Between 20% and 30% of people
with chronic hepatitis C develop cirrhosis after 20 years,
and 4% of these patients eventually develop liver cancer.
It should be noted that even in patients with cirrhosis,
survival rates in one study were nearly 80% at ten years.
Hepatitis C also can cause cryoglobulinemia, a condition
associated with lymphoma and kidney disease. Having a specific
genetic type of the virus may be the strongest factor in
predicting later liver damage. Genotype 1 is the most serious;
types 2 and 3 pose less danger. [See Box High Risk Hepatitis
Patients with chronic hepatitis C may be at higher risk
for other disorders including the following:
experts believe that hepatitis C may infect the central
nervous system in certain patients, possibly accounting
for the fatigue experienced by patients who have even relatively
Certain autoimmune disorders, particularly hypothyroidism
and rheumatoid arthritis.
Type 2 diabetes.
Not serious except in pregnant women, when it can be life
To date much research indicates it does not cause disease
or even increase the severity of any accompanying virus,
including HIV or other hepatitis viruses. Still, a few studies
indicate some risk for liver damage. More studies are needed.
of Patients with Autoimmune Hepatitis
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. One 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 the 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 as high, however, as with chronic viral hepatitis.
PRECAUTIONS SHOULD PEOPLE TAKE TO PREVENT HEPATITIS OR ITS TRANSMISSION?
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. [ See Table Life-Style Precautions
for Preventing Virus Transmission.]
Style Precautions for Preventing Virus Transmission
A and E.
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.
Sterilizing utensils or clothing is not necessary, but using
hot water and thorough cleanings are essential. Heating
a contaminated article for a minute kills the virus. Simple
household bleach is effective for disinfecting hard surfaces.
Still, utensils used by the patient for eating and cooking
should be kept separate from those used by others.
Patients with viral hepatitis should abstain from sexual
activity or take strict precautions if they cannot.
Abstain from alcohol. Moderate drinking (one or two drinks
per evening) after recovery is not harmful for most
B and C.
All objects contaminated by blood from patients with hepatitis
B or C must be handled with special care. (Restrictions
on food preparation are not necessary for these hepatitis
Patients with viral hepatitis should abstain from sexual
activity or take strict precautions if they cannot. 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 women partners or infected women should abstain from
sexual activity during menstruation. Either partner with
infections that cause bleeding in the genital or urinary
areas should avoid sexual activity until the infection is
no longer active.
C Section delivery in infected mothers appears to protect
the infants from contracting hepatitis C during delivery.
Infections when Traveling to High-Risk Countries
take the following precautions:
- Be vaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.)
against hepatitis A and sometimes B if traveling for long periods
of time to countries where epidemics occur.
- Use only
carbonated bottled water for brushing teeth and drinking. (It
should be noted that ice cubes can carry infection.) Boiling
water is the best method for eliminating infectious agents.
There is some debate about how long to boil, but bringing the
water to a good boil for at least a minute generally renders
it safe to drink.
food should be hot to the touch and eaten promptly.
buy food from street vendors.
of sliced fruit that may have been washed in contaminated water.
Travelers themselves should peel all fresh fruits and vegetables.
raw or undercooked meat and fish.
- more information
1 Travel to Developing
for Hepatitis A
(Havrix, Vaqta) are now available and both are very safe and effective
for preventing hepatitis A (HAV). They can be given along with immune
globulin and other vaccines. A 2001 study also strongly suggested
they may be used interchangeably (ie, if one is given as the first
vaccination, the other may safely be used as the booster). A combination
vaccine (Twinrix) that contains both Havrix and Engerix-B (a hepatitis
B vaccine) is now approved for people with risk factors for both
hepatitis A and B. [Also see hepatitis B below.]
Candidates for HAV Vaccinations. Vaccinations for hepatitis
A are recommended for the following individuals:
yet routinely given to children under two, the vaccine is proving
to be safe for infants. Infants who are born with the infection
from mothers with HAV have a lower response to the vaccines. Investigators
are also studying a higher-dose vaccine in these children. Early
results are promising.
in specific communities where outbreaks occur. Day care centers
are highly associated with such outbreaks, although risks in
such centers vary widely depending on the community, so universal
immunization in day care centers is not recommended.
active homosexual men.
with any form of chronic hepatitis. (It should be noted that
the HAV vaccination should be given to patients before they
reach advanced stages of liver disease, when there is a lower
rate of response.)
care workers exposed to the virus.
to developing countries. (Travelers should also receive immune
globulin if they are visiting high risk areas within four weeks
of the vaccination.)
now recommend routine vaccinations for children and adolescents
in high-risk states. These states are Arizona, Alaska, California,
Idaho, Nevada, New Mexico, Oklahoma, Oregon, South Dakota, Utah,
Washington, Missouri, Texas, Colorado, Arkansas, Montana, and
who have had intimate exposure to patients with hepatitis A
may be protected with immune globulin or possibly with the vaccine
- A recent
study suggested that the vaccine could be helpful in migrant
worker communities; this indication has not yet been officially
Side Effects . Although there are few side effects, allergic
responses from the vaccination can occur. Hair loss has been reported
in a very few people after a second administration. There may be
pain at the injection site. (Havrix causes more pain at the injection
site than Vaqta. )
for Hepatitis B
virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and
Engerix-B, can prevent hepatitis B (HBV) and are safe, even for
infants and children. A triple-antigen hepatitis B vaccine (Hepacare)
is proving to be effective for people who do not respond to the
standard vaccines. Vaccination programs are also proving to reduce
the risk for liver cancer. A combination vaccine (Twinrix) that
contains Engerix-B and Havrix, a hepatitis A vaccine, is now approved
for people with risk factors for both hepatitis A and B.
Until recently, the vaccine contained a mercury-based preservative
called thimerosal. In response to concerns, professional organizations
recommended suspending vaccinations in infants with noninfected
mothers. In September 1999, a thimerosal-free vaccine became available
and medical centers are now urged to continue vaccinations. Unfortunately
even after the thimerosal-free vaccine became available, a number
of hospitals still haven't restored vaccination of all infants.
This is a safe vaccine and it is reducing the need for hospitalization
in children. Parents should be sure their children are immunized.
Candidates for HBV Vaccinations. Experts now recommend that
all infants and children not previously vaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.) be immunized
by the time they reach seventh grade. Typical schedules for hepatitis
B vaccinations in childhood are as follows:
adults are at very high risk and should be vaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.):
- All infants
should receive the vaccine. High-risk infants (particularly
those with mothers infected with HBV) should be treated with
immune globulin and a series of vaccinations at birth, one month,
and six months. Low risk-infants should also be given the first
dose preferably at birth, and the second at four months, and
the third between six and 18 months later. (Children appear
be protected even if the booster shots are given a year apart
after the first dose, although high-risk children should still
be sure to receive their vaccinations on the short schedule.)
who are between 11 and 12 and who have not been immunized should
receive two or three doses of the vaccine (depending on the
brand) given over a few months. Evidence suggests that the two-dose
vaccine is very effective and may improve both costs and compliance
in adolescents compared to the three-dose regimen.
B vaccine protection lasts at least eight to 10 years. Booster
shots after that may be recommended depending on continuing
at risk who would benefit from vaccinations are the following:
and public safety workers who may be exposed to blood products,
such as from accidental needlesticks. Such individuals have
a risk for hepatitis B virus that ranges from 15% to 30%. (It
is unclear if patients, in general, have any significant risk
for infection for hepatitis C.)
in the same household as HBV infected individuals. (Unvaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.)
people who have had intimate exposure to people with HBV may
be protected with immune globulin, which is sometimes administered
with the vaccine.)
to developing countries.
who require transfusions and have not been infected with HBV.
(Those with blood clotting disorders should have the vaccination
administered under the skin not injected in the muscle.)
The regimen in
adults is typically three doses given over six months. One study
reported that older adults would benefit from a fourth dose without
incurring serious side effects. People with alcoholism may need
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 these people; it loses its effect
after five years in about a third of those who receive it.
active people with multiple partners.
and workers in mental institutions and morticians.
on hemodialysis. (People on hemodialysis may need larger doses
or boosters; they also may need to be revaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.) if blood
tests indicate they are losing immunity.)
who use injected drugs.
women at risk for the virus should be vaccinated (note: vaccines can cause irreversible health damage to the brain/body, and risks largely exceed any benefits. See SPECIAL REPORTS on vaccines. Please review all the evidence on vaccines before deciding to vaccinate yourself or your children.); there is no
evidence that the vaccine is dangerous to the fetus.
receiving treatments or who have conditions that suppress the
immune system may need the vaccination, although its benefits
for this group are unclear except for those at high risk, such
as people with HIV or spleen abnormalities.
Soreness at the injection site is the most common side effect. There
have been some reports of nerve inflammation after vaccinations
for hepatitis B, and there has been some concern about three small
studies associating the vaccine with an insignificant increase in
multiple sclerosis. Studies in 2001, however, have found no evidence
to support these concerns. Nonetheless, some groups oppose the vaccination
in children who are not in high-risk groups. It should be strongly
stressed that worldwide, 65 million people with chronic hepatitis
are expected to die from liver disease. And, vaccinations are saving
lives. For example, in Taiwan, where infection rates are high and
infants are at risk for hepatitis B from infected mothers, vaccination
programs have significantly reduced the risk for liver cancer.
of Hepatitis C
No vaccines are
available, but 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.
ARE THE MEASURES FOR MANAGING SYMPTOMS OF ACUTE HEPATITIS?
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
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. [ See What Precautions
Should People with Hepatitis Take? above.] The following
tips may be useful:
After 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 six months, a liver biopsy may be required to determine any
- 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 their regular diet.
- 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
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.
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.
- 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. Of special note, ibuprofen (Advil,
Motrin) apparently increases liver enzymes in hepatitis C patients
and therefore should be avoided. Ibuprofen is one the common
pain killers known as a nonsteroidal anti-inflammatory drugs
(NSAIDs). Other NSAIDs include aspirin and naproxen. The usual
alternative to an NSAID is acetaminophen (Tylenol). It should
be noted that acetaminophen also can be toxic in the liver,
particularly when drinking alcohol.
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,
have 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%.
ARE THE GUIDELINES FOR TREATING CHRONIC HEPATITIS?
Guidelines for Treating Chronic Hepatitis B and C
for chronic hepatitis B and C are aimed at reducing or preventing
liver damage and boosting or modifying the immune system to promote
its attack on the viruses. The important agents for treating chronic
hepatitis are interferons (particularly interferon alpha) and nucleoside
analogues (ribavirin, lamivudine, famciclovir, and adefovir), which
act directly against the virus. They are being used as sole therapy
and in combinations. These drugs are used differently depending
on the specific hepatitis. Other drugs with different mechanisms
are also being tested. [See individual discussions of treatments
for hepatitis B and C below.] Smokers with hepatitis C should make
every attempt to quit, as research now indicates that smoking is
associated with increased severity of the infection.
of Autoimmune Chronic Hepatitis
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. [See the individual discussion of treatments
for autoimmune hepatitis below.]
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
Description of Interferons
Types of Interferons
are natural proteins that activate certain immune functions
in the body and have anti-viral properties.
The natural interferons being used for chronic hepatitis
B, C or both are called type I interferons and include the
Interferon alpha 2b (Intron A). (Used for both hepatitis
B and C.)
Interferon alpha 2a (Roferon-A). (Mostly used for hepatitis
Interferon alfa-n1 (Wellferon). (Approved but mostly
used in Canada for hepatitis C.)
They are given by injection and need to be taken three
times a week.
Newer synthetic interferons have been developed that
are showing particularly promise:
Interferon alfacon-1 (Infergen). This agent is referred
to as a consensus interferon (CIFN) because it was genetically
developed using the most commonly occurring amino acid
sequences from each of the natural type 1 alpha interferons.
It is usually given three times a week when used as
initial treatment. CIFN is five to 10 times more biologically
active than natural type 1 interferons.
Pegylated interferon (PegINF). Pegylated interferons
employ a small molecule called polythelene glycol (PEG),
which attaches to a protein and extends the activity
of the interferon. This action allows the drug to be
taken only once a week. Currently only alfa-2b (Peg-Intron)
has been approved. PegINF alfa-2a (Pegasys) is waiting
who respond, studies are showing improved symptoms, a normal
long-term survival rate, and, in some, no return of the
Of note, some evidence suggests that even in the absence
of antiviral effects, interferon may reduce important factors
that contribute to cirrhosis, inflammation and fibrosis
(scarring). It may even have some effect on reversing liver
damage. If this evidence holds up, then even patients whose
viral and liver enzyme counts remain high or steady may
still benefit from long-term use of these agents.
Some studies also have suggested that interferon may help
prevent progression to liver cancer in hepatitis C (but
not hepatitis B) patients with early-stage cirrhosis.
For specific effects see How is Hepatitis B Treated?
or How Is Hepatitis C Treated?, below.]
for this treatment include the following:
patients include the following:
Those who have detectable levels of the virus and have
above-normal levels of alanine aminotransferase for
at least six months.
the percentage of patients who benefit over the long-term
using interferon as sole therapy is small.
Women who are pregnant or planning to become pregnant
Patients with advanced cirrhosis. (It is unclear if
the drug improves survival in patients with advanced
cirrhosis and, in any case, it may be dangerous for
Patients with fluid in the abdomen.
Patients, including children, with any serious medical
(particularly kidney, liver, autoimmune, or heart disease)
or psychiatric problems.
Enhancing the Effects
drugs may be used to enhance the effects:
drug combinations are used depending on the virus.
A very short course of corticosteroids may be used initially
in some cases to boost the effect of interferon.
Initial effects of the drug may also be enhanced in
certain patients by reducing iron levels through a series
of blood-drawings before starting interferon.
A 2001 study suggested that zinc supplements may boost
the effects of interferon.
hepatitis B and C, the disease often persists or returns
despite treatment. The virus continually generates many
"mutant viruses" that differ just slightly from the parent
virus. These mutated viruses may be resistant to interferons
and so, over time, the drugs become ineffective.
Side Effects and Complications
side effects of any interferon are flu-like symptoms (fever,
chills, muscle aches) that usually occur within six hours
and gradually decline over a week or two. (Pegylated interferon
may pose a higher risk for these symptoms than the natural
Chronic or more serious effects include the following:
have a difficult time with prolonged therapy. Over 20% drop
out if treatment lasts longer than two years. Depression
is the most common reason for withdrawal. (New long-acting
forms, such as pegylated interferon, may improve these drop-out
Emotional and mental changes. Depression can be very
severe and cases of suicidal thoughts have been reported.
Other mental and emotional symptoms include anxiety,
amnesia, confusion, irritability, impaired concentration,
decreased alertness, memory problems, and mental slowing.
Changes in sensation.
Gastrointestinal problems, including nausea, vomiting,
and diarrhea, and, in severe cases intestinal bleeding
Fatigue and general weakness.
Complications in the lungs, including exacerbation of
asthma. In severe cases, interferon can cause shortness
of breath, inflammation in the lungs, and pneumonia.
Possible negative effects on cholesterol and lipid levels.
Heart rhythm disturbances, which, in rare cases, can
Interferon often causes a drop in platelet and white
blood cell counts, increasing susceptibility to bacterial
May trigger an autoimmune response, possibly causing
anemia, diabetes, lupus-like symptoms, hypothyroidism,
or even autoimmune hepatitis.
Complications in the eye, including bleeding that, in
some cases, may lead to loss of vision if not detected
Rare reports of acute pancreatitis.
In children, interferon therapy temporarily disrupts
IS CHRONIC HEPATITIS B TREATED?
and nucleoside analogues are the important treatments at this time
for hepatitis B. At this time interferon alpha-2b is the standard
agent but experts expect the nucleoside analogue lamivudine to replace
it as the primary agent. Lamivudine is not only effective, it also
less expensive than the interferon. Researchers speculate that future
therapy for hepatitis B may need to involve combination treatment
to achieve the greatest possible viral reduction and to minimize
the chances of drug resistance.
Alpha for Hepatitis B
(Intron) is the standard drug for hepatitis B. It 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. (It does not appear to be effective for
hepatitis D.) Unfortunately, even in hepatitis B, 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. Interferon is
also effective in eligible children, although long-term effects
are unclear. A 2001 study suggested that it may temporarily disrupt
growth, but it should be noted that hepatitis itself, even without
interferon treatment, can compromise growth. [For a detailed description
of Interferon and eligibility, see Box Interferons.]
and Other Nucleoside Analogues
are drugs that can block viral replication, and they are important
in hepatitis B. The primary agent used in hepatitis is lamivudine.
It can be taken orally, has few severe side effects, and is less
expensive than interferon. Experts expect it to become the first-line
treatment for hepatitis B. Preliminary data suggest that other nucleoside
analogues, including ganciclovir, adefovir, entecavir, and famciclovir,
are also active against the hepatitis B virus and may useful in
combination to reduce drug resistance to lamivudine.
Success Rates. The nucleoside analogue lamivudine (Zeffix)
has reduced viral count in over half of hepatitis B patients who
have taken it as sole therapy for about a year. It also appears
to significantly reduce the risk for liver damage and cirrhosis.
The drug even suppresses hepatitis B viral replication in HIV-positive
patients and liver transplant recipients. It appears to be effective
for children as well as adults. The drug may reduce the risk for
cirrhosis, although it is not clear if it protects against liver
cancer, particularly in patients who have harbored the virus since
Loss of Effectiveness. Although response rates can be very
high for about a year, they tend to decrease with time in many patients.
This is caused by emergence of mutated viruses that are resistant
to the drug. Resistance may be particularly high in populations
where the virus is common, according to a Korean study from an area
where incidence of hepatitis B is high. The specific genetic hepatitis
B strain may be an important marker for predicting resistance. Other
nucleosides, such as adefovir and entecavir, may be able to suppress
these mutated viruses.
Side Effects. Lamivudine causes muscle aches and chills
but does not appear to have some of the distressing side effects
of interferon, such as depression, hair loss, weight loss, or a
drop in white blood cells (leukopenia). Of some concern, however,
is eventual resistance to the drug in many patients.
A number of drugs
are being studied that boost the body's own immune system to fight
Thymalfasin. Thymalfasin (Zadaxin) is a synthetic version
of a peptide derived from the thymus gland (which produces immune
factors call T-cells). It is injected and has few side effects.
It appears to be safe for hepatitis B patients when used alone or
in combination. Response rates of over 60% have been reported in
combination with an interferon. A trial using thymalfasin with lamivudine
is under way.
Vaccines as Treatments. Some hepatitis B vaccines, including
Hepagene, are being investigated for treating as well as preventing
Whey Protein. When a protein in milk called casein coagulates,
a watery liquid called whey and solid white lumps called curds form.
(Curds are the basis for cheese.) One interesting trial studied
patients who consumed a supplement made from whey (Immunocal) twice
a day. After 12 weeks hepatitis B patients showed improved biochemical
measurements indicating possible benefits on the disease process.
(It had no effect on hepatitis C patients.)
IS HEPATITIS C TREATED?
Alone and in Combination with Ribavirin for Hepatitis C
alone or with ribavirin (a nucleoside analogue), is the only treatment
now available for chronic hepatitis C. The goal of this treatment
is to reduce viral levels to zero.
Specific Agents Used. A number of natural and synthetic
interferons are now available or awaiting approval for hepatitis
C. They can be used alone in some cases or in a combination with
ribavirin (Rebetol), a nucleoside analogue. Ribavirin is poor at
inducing initial responses alone but it can double sustained response
rates when combined with interferon. Interferons being use are the
Natural interferons used in the US for hepatitis C including the
include the following:
alpha-2a (Intron). The combination of interferon alpha-2b and
ribavirin is available as Rebetron. This combination is showing
double the success rates of interferon alone.
(Infergen) This agent, also called consensus interferon, is
now approved for hepatitis C.
interferons. These synthetic agents are a long-acting formulation
of either interferon 2a or 2b. Currently alfa-2b (Peg-Intron)
is the only pegylated interferon approved in the US. It is available
alone or in combination with ribavirin (Rebetol) for hepatitis
C adult patients not previously treated with interferon alfa
and who have early-stage liver disease. Approval for alfa-2a
(Pegasys) has been delayed as of the date of this report. Some
evidence suggests that PegINF may produce a unique response,
a rapid first phase and a second slower phase.
Interferon alone has been successful in inducing a good initial
response in chronic hepatitis, although it does not usually sustain
this response over time. There is even some evidence to suggest
that interferons may be used during the acute stage to prevent
chronic hepatitis. Interferon combinations with ribavirin and other
investigative agents are improving early sustained response times
in patients with chronic hepatitis C. Combinations with the newer
synthetic interferons are particularly promising. It should be noted,
however, that combinations have more side effects and are less well
tolerated than interferon alone. Some studies have also suggested
that interferon may help prevent progression to liver cancer in
hepatitis C patients with early-stage cirrhosis. (A higher total
dose, rather than a longer duration of treatment, appears to be
the critical factor for protection.) In patients who have been treated
for hepatitis-C related liver cancer, one small study also suggested
that interferon may help prevent cancer recurrence after tumor removal.
[For a specific information see Boxes Description
of Interferons and Response Rates
in Hepatitis C Patients Receiving Interferons and Their Combinations
Candidates. The best hepatitis C candidates for interferon
treatments are those at greatest risk for cirrhosis. Patients with
mild disease, particularly those with normal liver enzyme (transaminase)
levels, may not need treatment at all. People with early stage (compensated)
cirrhosis may be good candidates for interferon combination treatments,
including with the newer interferon forms, particularly PEG-IFN.
Factors suggesting a higher risk for cirrhosis include the following:
are not good candidates and are usually ineligible are the following:
virus levels as determined by an assay test.
- High levels
of aminotransferase enzyme for more than six months. (Those
with normal liver enzyme levels appear to have almost no risk
for liver damage, even if the virus is evident.)
of liver scarring.
degree of liver inflammation and severe tissue damage.
of children to interferon appears to be similar to those in adults,
although large studies are needed to confirm this.
who are pregnant or planning to become pregnant soon. (The combination
therapy poses a particular risk for unborn children.)
with advanced cirrhosis. It is unclear if the drug improves
survival in patients with advanced cirrhosis and, in any case,
it may be dangerous for them.
with fluid in the abdomen.
with any serious psychiatric problems.
abusers. Although patients with addictions to drugs, alcohol,
or both are not medically ineligible for antiviral treatment,
their psychologic side effects of interferon can be very severe,
sustained response rates are low, and their compliance to treatment
regimens is often poor. Most physicians then will not treat
this patient group until their addictions have been treated.
Nevertheless, with careful monitoring, a 2001 study reported
that patients with drug addiction but no other severe psychologic
problems may be treated successfully and achieve sustained responses
similar to other patients.
with kidney or heart disease.
with anemia or risk factors for anemia. These patients should
not take the combination treatment, although they may be candidates
for interferon alone.
Side Effects of the Combination Treatment. The side effects
of interferon alone, discussed above, may occur more often in the
combination treatment. [ See Box Description
Ribavirin used in the combination treatment adds the following side
from the combination result in treatment discontinuation in 8% to
21% of patients. The most frequent reason in the US is from depression.
anemia. It is reversible and usually stabilizes after a month
or two of treatment. However, some patients may become so anemic
that they have to withdraw. This effect can also worsen heart
disease and so patients with a history of significant heart
problems should not be treated with ribavirin.
- Skin disorders.
and shortness of breath.
and neurologic symptoms, such as severe sleep disturbances,
depression, and anxiety.
symptoms (heartburn, and weight loss).
thyroid dysfunction (either over or under activity).
- The combination
of both drugs poses a very high risk for birth defects in children
whose mothers used the drugs while pregnant.
Treatment Success with Interferon or the Ribavirin Combination
treatment success and approaches based on different factors, including
It should be
noted that the disease often persists or returns despite treatment.
The virus continually generates many mutant viruses that differ
just slightly from the parent virus. These variants, known as quasispecies,
can remain unaffected by antiviral agents, including interferon.
Some experts believe that this may be due to the wide fluctuations
in current interferon treatment, which allow mutations to evolve
during the periods when the drug is at low levels in the blood stream.
It should be noted that patients with normal liver enzyme levels
appear to have almost no risk for liver damage, even if viral levels
persist after treatment.
- If the
patient responds to the drug right away (responders).
the response is sustained (sustained response).
the virus comes back again and requires retreatment (relapsing
The approach to treatment with interferon or combinations is multi-leveled
depending on whether the patient has had no prior treatment, if
the patient achieves a sustained response, if the patient relapses
and needs retreatment, or if the patient has not responded. [For
specific study results on these treatment phases see Table
Response Rates in Hepatitis C Patients Receiving
Interferons and Combinations.]
Responders. Patients are considered responders when their
viral count drops very rapidly within the first few weeks of treatment
and it is still undetectable at 12 weeks. One difficulty in deciding
when to stop treatment even in responders is the inability to predict
at 12 weeks which of these patients will relapse and which ones
will have sustained response.
Some factors that reduce the chances for a both a first and sustained
response are as follows:
have a significantly lower response rate than other ethnic groups.
Researchers do not yet understand the cause of this disparity, although
one theory is that they may have a higher rate of co-infection with
the aggressive viral genotype 1.
a high viral load (more than 2 million/mL). Extending treatment
in such people can often nearly duplicate the responses achieved
by patients with lower viral loads.
- The presence
Sustained Responders. Patients who are free of the virus
longer than six months are considered to be sustained responders.
Between 90% and 95% of these patients remain free of the infection
for at least four to 10 years. Unfortunately, less than half of
treated patients are sustained responders. The factors that increase
or reduce the chances for a sustained response are also the same
as those having an initial response [ see above ]. It should
be noted that dramatically fewer African-American patients (2% to
3%) achieve a sustained response than Caucasian (12%) or Asian (28%)
Relapsing Patients. A relapse occurs in patients who respond
initially but the disease recurs, most likely because of the development
of mutant strains that may be resistant to the drugs used or because
the original dose was too low.
Nonresponders. Patients are considered to be nonresponders
if the virus is still detectable 12 weeks after interferon alone
or 24 weeks of combination therapy. In general, physicians stop
treatment at this point. However, failure can be due to different
factors that should be assessed before stopping treatment, particularly
in patients who had interferon alone:
or testing alternative treatments may be an option for some patients,
particularly those who had a so-called breakthrough at some
point in the initial treatment. (During a breakthrough there is
a temporary reduction in liver enzymes or disappearance of the virus.)
It should also be noted that there is some evidence that interferon
still reduces liver scarring and may even reduce the risk for liver
cancer in some patients even if the treatment does not eliminate
dose is too low.
did not comply fully with the treatment.
was consuming alcohol.
Rates in Hepatitis C Patients Receiving Interferons and Their
Response Rates for Initial Treatment
Rates for Retreatment of Relapsing Patients
Rates for Retreatment of Nonresponders
Inteferons (sole therapy)
Standard interferon at standard doses for six months: 7%
to 20% sustained responders. Standard interferon alone taken
for 12 to 24 months: 15% to 30%. (Not generally effective
in patients with genotype 1.)
A higher dose of interferon in patients. (Retreatment at
the standard dose achieves only a 4% response.)
Little benefit from sole therapy. Studies suggest a significant
and rapid reduction in viral levels, with daily high doses
of interferon, but the effects do not appear to be sustained
when the patients return to a three-times-weekly regimen.
Natural Interferons plus ribavirin
Combination interferon and ribavirin: 30% to 40% sustained
responders. (48 weeks of combination therapy may be the
best option for patients with genotype 1.)
Response rates are from 30% to 49%.
Overall response rates in patients who failed interferon
alone are less than 20%. In genotype 2 and 3, response rates
can be about 30%. Higher doses of interferon may be needed
for any significant response in patients with genotype 1
(18% for high doses versus 7% with lower doses in one study.)
interferon (PEGINF) (sole therapy)
Pegylated interferon (PEGIFN) alone, either alfa 2a or 2b:
Sustained response of 39%. Better sustained responses than
standard interferon alone. (In one study, 30% of patients
with cirrhosis had a sustained response with PEGIFN alfa-2a.)
PEGINF plus ribavirin
Combination pegylated interferon alfa-2b (Peg-Intron) and
ribavirin (Rebetol) has been approved. In one study 56%
sustained response, higher than interferon combination.
It was effective even in genotype 1 patients.
alfacon-1 (consensus interferon)
12% to 20% sustained responders. Overall rates similar to
interferon alpha 2b but it was significantly better for
patients with HCV genotype 1 (7% versus 0). One small study
report a 55% sustained response with consensus interferon
plus ribavirin in patients with type 1 genotype.
58% response rate after 48 weeks (one study).
Response rate of 13% (one study).
Approaches using Interferon
In a 2001 study an interferon/amantadine achieved a sustained
response of 45.5% compared to 28.7% with interferon alone.
Triple therapy (interferon alfa, ribavirin, and amantadine).
Early studies were promising but later results could not
confirm these early successes. More research is needed.
[ See Amantadine, below.]
Drugs for Hepatitis C
Amantadine (Symmetrel) is a drug commonly used for Parkinson's
disease, but which may have some antiviral effects. Investigators
are studying combinations of amantadine with interferon and triple
therapy with interferon and ribavirin. More research is needed to
determine if they have significant benefits. [See Table Response
Rates in Hepatitis C Patients Receiving Interferons and Their Combinations.]
In some cases, the side effects of amantadine can be severe, and
include vertigo, insomnia, nervousness, and depression. They are
particularly disabling among older patients who receive inappropriately
Thymalfasin. Thymalfasin (Zadaxin) is a synthetic version
of a peptide derived from the thymus gland (which is responsible
for maturation of immune factors call T-cells). It is being used
for hepatitis B and is under investigation for hepatitis C in combinations
with natural interferons and pegylated interferon.
Ursodeoxycholic Acid. Ursodiol, or ursodeoxycholic
acid, a drug ordinarily used for gallstones, improves aminotransferase
levels. It has no effect against the virus, but may be useful in
combination with interferon.
Protease Inhibitors. Protease inhibitors (similar to those
used for HIV) are under investigation for hepatitis C patients who
fail other treatments. They are especially useful in patients who
are infected with both viruses.
with serious or chronic diseases are now investigating alternative
Among the natural substances being investigated for hepatitis are
ginseng, glycyrrhizin (a compound in licorice), catechin (found
in green tea), and silymarin (found in milk thistle). A 2001 review
analyzed studies on ten herbal remedies for hepatitis C. None showed
significant benefits except silymarin, which improve liver enzyme
levels. Other studies are also reporting benefits on the liver from
Chinese herbal medicines, including bing gan ling, yi zhu, and yi
er gan tang, also appeared to be beneficial. Of specific concern,
however, are studies suggesting that up to 30% of herbal patent
remedies imported from China having been laced with potent pharmaceuticals
such as phenacetin and steroids. Most problems reported occur in
herbal remedies imported from Asia, with one study reporting a significant
percentage of such remedies containing toxic metals. Patients interested
in these remedies should ask their physicians about clinical studies.
It should be strongly noted that herbal remedies are not necessarily
harmless simply because they are natural (or marketed as natural),
and their quality is not regulated except in clinical studies. [
See Box Warnings on Alternative and So-Called
Warnings on Alternative and So-Called Natural Remedies
be strongly noted that alternative or natural remedies are
not regulated and their quality is not publicly controlled.
In addition, any substance that can affect the body's chemistry
can, like any drug, produce side effects that may be harmful.
Even if studies report positive benefits from herbal remedies,
the compounds used in such studies are, in most cases, not
what are being marketed to the public.
There have been a number of reported cases of serious and
even lethal side effects from herbal products. In addition,
some so-called natural remedies were found to contain standard
The following warnings are of particular importance for
people with hepatitis:
website is building a database of natural remedy brands
that it tests and rates. Not all are available yet. https://www.ConsumerLab.com/
Kava kava (an herb used for anxiety and tension) can
be toxic to the liver and cause severe hepatitis and
even liver failure if taken excessively.
Black licorice (not the red candy) can increase blood
pressure and may be harmful in people with hypertension.
The Food and Drug Administration has a program called MEDWATCH
for people to report adverse reactions to untested substances,
such as herbal remedies and vitamins (call 800-332-1088).
ARE THE TREATMENTS FOR AUTOIMMUNE HEPATITIS?
About 85% of
people with chronic active autoimmune hepatitis do not have severe
symptoms at all. In these cases, physicians often must weigh the
risk for progression to a more serious condition against the long-term
adverse effects of the treatments used for autoimmune hepatitis.
Because of effective treatment options and in spite a high rate
of relapse, long-term survival rates in patients with autoimmune
hepatitis are excellent.
are agents that block factors in the immune system and help reduce
inflammation and symptoms of autoimmune hepatitis.
Corticosteroids. Corticosteroids, prednisone and prednisolone,
are the standard agents. They produce remission of symptoms in about
80% of patients with autoimmune hepatitis. For most patients, steroids
also 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.
(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.)
Treatment usually needs to continue for about two years before the
disease is in complete remission. 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 (decompensated) cirrhosis are not good candidates for this
Unfortunately, remission rarely lasts more than three years. 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.
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,
Azathioprine. 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. 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
Cyclosporine A. Cyclosporine A (Neoral) is another immunosuppressant
and may prove to be a safe and effective alternative to corticosteroids.
If all therapies
fail and the disease becomes life threatening, liver transplantation
may be performed.
IS LIVER TRANSPLANTATION NEEDED?
may be indicated in the following patients:
survival rates after liver transplantation are between 60% and 80%.
Patients also report improved quality of life and mental functioning
after liver transplantation. Patients should seek medical centers
that have performed more than 50 transplants per year and produced
who have developed life-threatening cirrhosis and who have a
life expectancy of more than 12 years.
with liver cancer that has not spread beyond the liver may also
Unfortunately, in about half of all chronic hepatitis patients,
the disease recurs.
At the time of
this report, 18,700 patients were waiting for a liver transplant.
Only about 5,000 transplants were performed in 2000. And, given
the large number of people with hepatitis C, this situation will
almost certainly worsen over the following years.
- One study
of patients with hepatitis C reported five year risks for viral
recurrence of 80% and for cirrhosis of 10%.
recurrence is also high in hepatitis B patients. Recurrence
in hepatitis B has been significantly reduced using monthly
infusions of hepatitis B immune globulin (HBIg), with or without
lamivudine. These injections may need to be administered life
long. Lamivudine may also be helpful in preventing recurrence
of hepatitis B after liver transplantation in children as well
quarters of the patients who receive transplant for autoimmune
hepatitis experienced organ rejection, and half required retransplantation
within a year. Autoimmune hepatitis recurred in 25% of patients
studied. (According to one 2000 study, transplantation in these
patients may improve accompanying autoimmune disorders in half
of patients who experienced it.) Children who develop autoimmune
hepatitis after liver transplantation may respond to corticosteroid
and azathioprine therapy.
ELSE CAN HELP FOR HEPATITIS BE FOUND?
of Diabetes and Digestive and Kidney Diseases (NIDDK), Office of
Communications and Public Liaison, NIDDK, NIH, Building 31, Room
9A04, 31 Center Drive, MSC 2560, Bethesda, MD 20892-2560 or on the
Centers for Disease Control and Prevention, Hepatitis Branch, 1600
Clifton Road NE., Mail Stop G37, Atlanta, GA 30333. For a special
number on hepatitis Call (888-4HE-PCDC) or (888-443-7232) or on
the Internet (https://www.cdc.gov/ncidod/diseases/index_eh.htm#h)
Scroll down to "Hepatitis."
This is an important source on hepatitis.
American Association for the Study of Liver Diseases, 1729 King
Street, Suite 100, Alexandria, VA 22314 Call (703-299-9766) or on
the Internet (https://www.aasld.org)
This group publishes the journal Hepatology. For abstracts on the
Hepatitis Foundation International, 30 Sunrise Terrace, Cedar Grove,
New Jersey 07009 Call (800-891-0707) or (973-239-1035) or on the
This organization focuses just on viral hepatitis. It provides educational
materials, offers support by phone, and gives referral to other
American Liver Foundation, 75 Maiden Lane, Suite 603, New York,
NY 10038 Call (800-GO LIVER) or (800-465-4837) or on the Internet
The foundation has regional chapters, some with support groups.
The hepatitis hotline provides patient information, brochures, and
video and audio tapes.
American Gastrointestinal Association, 7910 Woodmont Ave., Seventh
Floor, Bethesda, MD 20814. Call (301-654-2055) or on the Internet
This is an association for physicians and other professionals. They
provide names of gastroenterologists in local areas.
Immunization Action Coalition, 1573 Selby Avenue, Suite 234, St.
Paul MN 55104 Call (651-647-9009) or on the Internet (https://www.immunize.org/)
On the Internet:
The Hepatitis Information Network (https://www.hepnet.com/)
Hepatitis Central (https://hepatitis-central.com/)
For information on organ transplantation, United Network for Organ
Excellent site on liver diseases from Columbia-Presbyterian Medical
A patient-to-patient support forum: (https://www.medhelp.org/perl6/Hepatitis/wwwboard.html)