Transcript CLINICAL PHARMACY IN HEPATOLOGY

CLINICAL PHARMACY IN
HEPATOLOGY
THE LIVER
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The liver is the largest organ in the body. It is found
high in the right upper abdomen, behind the ribs. It is a
very complex organ and has many functions. They include:
Storing energy in the form of sugar (glucose)
Storing vitamins, iron, and other minerals
Making proteins, including blood clotting factors, to keep
the body healthy and help it grow
Processing worn out red blood cells
Making bile which is needed for food digestion
Metabolizing or breaking down many medications and
alcohol
Killing germs that enter the body through the intestine
The liver shoulders a heavy work load for the body, and
almost never complains. It even has a remarkable power to
regenerate itself. Still, it should not be taken for granted.
The liver is subject to illnesses that can lead to permanent
damage. One example is autoimmune hepatitis, a condition
in which the body fights against its own liver.
Hepatitis
When cells in the body are injured by such things as
chemicals or infection, the area that is wounded becomes
inflamed. Hepatitis is inflammation of the liver, which in
turn causes damage to individual liver cells. It is most often
caused by viral infection. However, it can also be caused by
alcohol, certain drugs, chemicals or poisons, or other
diseases.
Hepatitis may be either acute or chronic. In acute hepatitis,
the inflammation develops quickly and lasts only a short
period of time. The patient usually recovers completely, but
it can take up to several months. Occasionally, a person fails
to recover fully, and the hepatitis becomes chronic. In other
words, it continues at a smoldering pace. Chronic hepatitis
can develop over a number of years without the patient
ever having acute hepatitis or even feeling sick. As the liver
repairs itself, fibrous tissue develops, much like a scar
forms after a cut or injury to the skin heals. Advanced
scarring of the liver is called cirrhosis. Over time, cirrhosis
irreversibly damages the liver, eventually ending in liver
failure.
Types of Viral Hepatitis
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Type A -- Previously known as infectious hepatitis, it can be contracted
through contaminated water or food. During the acute infection, the
patient's blood and body fluids are also infectious. Although some
patients become acutely and desperately sick from this infection, most
people tolerate it well and fully recover. No chronic infection occurs
with this virus.
Type B -- Previously known as serum hepatitis. Patients are sicker
initially with this very unpleasant virus and take longer to recover,
some-times several months. Furthermore, about 10 percent of patients
progress into a state of chronic smoldering infection in the liver. A
person can be infected by a contaminated needle or through sexual
contact. Homosexual men, intravenous drug users, or persons who have
sexual contact with these people are at an especially high risk for
contracting this disease.
Type C -- This virus infection was previously known as non-A non-B
hepatitis. In the past, it was transmitted mostly by blood transfusion.
There are now good blood tests to check for this virus before blood is
given. Most cases now occur in people who use contaminated needles
for drug use. However, many cases are "community acquired," meaning
the physicians really don't know how they occur. It is difficult, but not
impossible, to transmit this virus by unprotected sexual intercourse.
Many people who acquire this infection go on to a chronic phase.
Other Viruses -- There are now types recognized -- D, E, and G viruses -that can cause hepatitis. Infectious mono virus, CMV virus, and several
other viruses are also capable of infecting the liver.
Viral Hepatitis. Symptoms
As with other illnesses, symptoms of hepatitis can
be severe, mild, or not present at all. It depends on
how badly the liver is damaged. With mild viral
hepatitis, slight fatigue may be the only symptom.
When hepatitis is severe, the patient loses the taste for
food and cigarettes, develops a heaviness in the rightupper abdomen and, especially with acute B hepatitis,
may have diarrhea and arthritis. The liver and even the
spleen can enlarge. jaundice then develops. The eyes
and skin turn yellow, the urine dark, and the stool a
putty-white color. Jaundice results when the yellow bile
pigment, which normally flows through the bile ducts to
the intestine, backs up and spills into the blood. Acute
hepatitis can last from two weeks to several months.
The patient often needs to be hospitalized in the early,
acute phase of the illness.
Hepatitis B is caused by the hepatitis B virus (HBV). Current
estimates are that over 250,000 people in the United States
contract HBV each year. It is often spread through sexual
contact, accounting for about 50% of the reported cases. It is
also spread through contact with blood or body fluids from a
person carrying HBV. Some groups have a higher risk of
becoming infected with HBV. These include:
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Intravenous drug users
Health care workers, funeral workers, police
People in an HBV infected person's household
People with multiple heterosexual or, especially,
homosexual partners
Residents of nursing homes
Hemophiliac and hemodialysis patients
Prisoners and prison workers
Travelers to underdeveloped countries
Certain ethnic groups such as Asians, Hispanics,
American Indians, Alaskan Natives, or people from
developing countries
The following are symptoms of acute hepatitis B:
Loss of appetite, nausea, vomiting, fever
Aching muscles and sometimes joint pain
Tenderness in the right upper abdomen
Jaundice (yellowing of skin and eyes)
Tea-colored urine; putty-like or white stool
Diagnosis of the disease is made by a blood test. It is called the
hepatitis B surface antigen test (HBsAg). No specific treatment is
available or usually necessary for acute hepatitis infection. The
physician may recommend supportive measures to help the patient
maintain strength and avoid taxing the liver while the body's natural
defenses are fighting the virus. Acute hepatitis B patients recover
completely within six months and develop antibodies that give them
a life-long immunity.
Some patients who become infected, however, do not recover
completely. Up to 10% of adults with Hepatitis B and up to 50% of
infected children under five years of age are not able to completely
fight off the virus within six months. This occurs because their
bodies are unable to develop antibodies against hepatitis B. Most of
these patients become HBV carriers.
Vaccination
Passive (short-acting) and active (permanent and
long-lasting) vaccines now are available against
hepatitis A and B. People who travel to
underdeveloped countries are encouraged to
receive these vaccinations. The following high-risk
groups should also receive active immunization:
health care workers, especially those who handle
body fluids such as blood; people who have
multiple sex partners; intravenous drug users; and
prostitutes. The American Pediatric Association now
recommends that all infants and children be
vaccinated.
Prevention
There are precautions people should take to protect
themselves against hepatitis B. Since the virus is most often
spread through sexual contact, it is most important to avoid
unprotected sex with those who have or are likely to have the
infection. Precautions must be taken to avoid coming in
contact with blood or body fluids from an infected individual.
For those living in households with infected patients, surfaces
which may hold the virus should be cleaned with one part
household bleach to 10 parts water. Items such as razors,
toothbrushes, IV needles or pierced earrings should never be
shared. People should also avoid such practices as tattooing
and ear piercing in places where sterile conditions are
questionable. Women who are pregnant should be tested for
HBV and follow their physicians' advice to protect their unborn
children.
Chronic hepatitis B (a smaller
percentage of patients who cannot fight off the virus will
develop chronic hepatitis B)
Patients with chronic hepatitis B should avoid alcohol because it can
cause additional liver damage. Some medicines and drug
combinations may cause liver injury, so patients should review all
medications they are taking with their physicians. Patients should
never take over-the-counter drugs without the physician's approval.
Chronic hepatitis B can now be treated with interferon (trade
name: Intron A). Some patients, however, are not good candidates
for interferon therapy. A liver disease specialist is often required to
determine if the patient should be placed on this therapy.
Interferon has been shown to reduce inflammation and liver
damage in about 30% of treated patients. A few go on to
apparent complete recovery. In some, however, the disease returns
when therapy is stopped, and treatment may have to be restarted.
There are bothersome side effects with the drug, and treatment
must be evaluated with the physician on an individual basis.
Autoimmune Hepatitis
The immune system consists of different types of white
blood cells that help to fight infections. Some of these cells
produce antibodies. Antibodies act as warriors. They defend
the body by destroying bacteria, viruses and other foreign
materials. There are different kinds of antibodies, each
fighting against a specific foreign substance. Thus, the
immune system protects the body against outside invasion
by germs. But sometimes, the immune system mistakenly
recognizes the body's own organs as foreign. It can develop
antibodies against these organs. This can cause various
illnesses, such as rheumatoid arthritis and lupus. These
illnesses are called autoimmune disorders because the body
is literally fighting against itself.
When the immune system attacks the liver in this way, it is
called autoimmune hepatitis. Autoimmune hepatitis is not
caused by a virus or bacteria, so it is not a contagious
disease. Exactly what triggers the immune system against
the liver is unknown. The inflammation is usually chronic,
and without treatment it can cause serious injury to the
liver.
Autoimmune Hepatitis (cont’d)
Symptoms and Diagnosis
Autoimmune hepatitis occurs mainly in adolescent or young adult
women (about 70% of the time). However, there have also been
cases of older women and men developing the disease. Early
symptoms are the same as those for most types of hepatitis: fatigue,
abdominal discomfort, and aching joints. These early symptoms are
sometimes mild and mistaken for other illnesses, such as the flu. So,
it is wise for people with these symptoms to consult a physician.
When autoimmune hepatitis progresses to severe cirrhosis, there may
be jaundice (yellow coloring to the skin and eyes), marked swelling of
the abdomen from fluid inside the abdomen, intestinal bleeding, or
mental confusion.
The physician often suspects autoimmune hepatitis from the patient's
medical history. For example, patients with other autoimmune
diseases -- thyroiditis, ulcerative colitis, diabetes mellitus, vitiligo (a
patchy loss of pigment in the skin), Sjogren's syndrome (a condition
causing dry eyes and mouth) -- are more likely to have autoimmune
hepatitis.
Autoimmune Hepatitis (cont’d)
Symptoms and Diagnosis
A definite diagnosis of autoimmune hepatitis is
obtained with blood testing. Two antibodies that
may develop in the blood are the ANA
(antinuclear antibody) and the SMA (smooth
muscle antibody). Also, a certain type of blood
protein called gamma globulin is frequently
elevated. A liver biopsy is always needed to
determine how much inflammation and scarring has
developed. This exam is performed under local
anesthesia. A slender needle is inserted through the
right lower chest to extract a small piece of liver
tissue. The tissue is then examined under a
microscope. This information allows the physician
to tailor the treatment to each individual patient.
Autoimmune Hepatitis (cont’d)
Treatment
The treatment of autoimmune hepatitis is aimed at curbing the
autoimmune response, and therefore the damage to liver cells.
It is most effective when begun at an early stage of the disease.
In most cases, the initial treatment is with a cortisone drug,
usually prednisone (trade names: Deltasone, Orasone).
Sometimes a second drug, such as Imuran, may be added.
The medication is taken daily, usually for at least a year. The
physician may attempt to taper and stop treatment if the
patient is doing well. However, a relapse often occurs, and the
medication then must be restarted and taken indefinitely. The
physician uses the lowest dosage possible to decrease
symptoms, improve liver tests, and slow liver damage.
Unfortunately, a few patients do not respond well to treatment,
especially if the disease is diagnosed late and cirrhosis is well
advanced. When the patient no longer responds to treatment
with medication and liver damage is severe, a liver transplant is
considered.
Cirrhosis
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Many types of chronic
injury to the liver can
result in scar tissue.
This scarring distorts
the normal structure
and regrowth of liver
cells. The flow of blood
through the liver from
the intestine is blocked
and the work done by
the liver, such as
processing drugs or
producing proteins, is
hindered.
Cirrhosis can be caused by many
things, some known and others
unknown:
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Alcohol -- Using alcohol in excess is the most common cause of cirrhosis in the
United States.
Chronic Viral Hepatitis -- Type B and Type C hepatitis, and perhaps other
viruses, can infect and damage the liver over a prolonged time and eventually
cause cirrhosis.
Chronic Bile Duct Blockage -- This condition can occur at birth (biliary atresia)
or develop later in life (primary biliary cirrhosis). The cause of the latter
remains unknown. When the bile ducts outside the liver become narrowed and
blocked, the condition is called primary sclerosing cholangitis. This condition is
often associated with chronic ulceration of the colon (colitis).
Abnormal Storage of Copper (Wilson's Disease) or Iron (Hemochromatosis) -These metals are present in all body cells. When abnormal amounts of them
accumulate in the liver, scarring and cirrhosis may develop.
Drugs and Toxins -- Prolonged exposure to certain chemicals or drugs can scar
the liver.
Autoimmune Hepatitis -- This chronic inflammation occurs when the body's
protective antibodies fail to recognize the liver as its own tissue. The
antibodies injure the liver cells as though they were a foreign protein or
bacteria.
Cystic Fibrosis and Alpha l-antitrypsin Deficiency -- These disorders are
inherited.
Cirrhosis. Signs and Symptoms
Cirrhosis takes years to develop. During this time, there are usually
no symptoms, although fatigue, weakness and decreased appetite
may occur and worsen with time. When cirrhosis is fully developed,
a number of signs may be present:
 Fluid retention in the legs and abdomen -The liver produces a protein, called albumin, that holds fluid in blood
vessels. When the blood level of albumen falls, fluid seeps out of the
tissues into the legs and abdomen, causing edema (fluid
accumulation) and swelling.
 Jaundice -The liver produces bile that normally flows into the intestine.With
advanced cirrhosis, bile can back up into the blood, causing the skin
and eyes to turn yellow and the urine to darken.
 Intense Itching -Certain types of cirrhosis, such as chronic bile duct blockage, can
produce troublesome itching.
Cirrhosis. Signs and Symptoms
Gallstones -Cirrhosis causes the abnormal metabolism of bile pigment. Because of
this, gallstones develop twice as often in cirrhosis patients as in
those without the disorder.
 Coagulation Defects -The liver makes certain proteins that help clot blood. When these
proteins are deficient, excessive or prolonged bleeding happens.
 Mental Function Change -The liver processes toxins from the intestine. When these substances
escape into the bloodstream, as occurs in severe cases of cirrhosis,
a variety of changes in mental function can develop.
 Esophageal Vein Bleeding -In advanced cirrhosis, intestinal blood bypasses the liver and flows up
and around the esophagus (the food tube) to the heart. The veins
in the esophagus dilate (widen) and may rupture, causing slow or
massive intestinal bleeding.
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Cirrhosis. Prevention
Perhaps 90 percent of cirrhosis is caused by
excessive alcohol consumption or hepatitis viruses.
Of course, alcohol can be avoided. Alcohol
consumption should always be limited to no more
than 1 or 2 drinks per day. And type B hepatitis
now has an effective vaccine against it. Vaccination
against B hepatitis virus is safe and inexpensive. It
should be taken especially by certain high-risk
groups: all health care professionals, persons
traveling to third world countries, homosexuals,
intravenous drug users, and prostitutes.
Cirrhosis. Treatment
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The alcoholic patient must permanently stop consuming alcohol.
When iron is being retained in the body, chronic removal of blood by
vein eliminates large amounts of iron.
Cortisone medicine helps treat autoimmune hepatitis and cirrhosis.
Restricting salt and using fluid pills (diuretics ) reduce edema and
abdominal swelling.
Toxins and injurious drugs must be avoided.
Decreasing dietary protein and using certain laxatives generally can
prevent changes in mental function.
Bleeding veins in the esophagus can be injected with sclerosing
(clotting) agents or closed with small rubber bands. Occasionally,
surgery is necessary to prevent recurrent massive bleeding.
Ursodiol (Actigall) and other drugs have been helpful in treating
primary biliary cirrhosis and primary sclerosing cholangitis.
Liver transplantation has progressed to the stage where it can now
be considered as standard treatment for selected patients.
Chronic pancreatitis
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There is no cure for chronic pancreatitis. Once the pancreas is
damaged, then it is not able to return to normal function and there
is always the potential for further attacks. Treatment is, therefore,
directed towards preventing attacks, controlling the pain and
treating the complications.
Preventing symptoms worsening
Patients with chronic pancreatitis should avoid alcohol altogether. If
the pancreatitis is due to excess alcohol consumption, then this is
essential. If it is due to other causes, then it seems sensible to avoid
a substance which is capable of damaging the pancreas.
If an underlying cause has been identified then this should be
treated. Disorders of calcium metabolism and of fat metabolism will
be treated appropriately. Your doctor may recommend removal of
the gall bladder if pancreatitis is thought to be caused by gall
stones.
Chronic pancreatitis
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Preventing attacks
The long-standing principle has been to try and rest the
pancreas. This involves giving pancreatic supplements such as
Creon (which contain pancreatic enzymes in high
concentration) together with drugs which reduce acid
secretion by the stomach. Patients should also follow a low-fat
diet.
These measures reduce the presence of fat in the duodenum,
reduce acid in the duodenum and reduce the need for
pancreatic enzyme secretion. These measures are very
successful in about a third of patients, moderately successful
in a third and unhelpful in a third.
Some eminent specialists have supported the use of
antioxidants in the treatment of chronic pancreatitis. These
antioxidants include selenium and vitamin C.
Chronic pancreatitis
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Control of pain
This is a very important aspect of the treatment of chronic
pancreatitis. Pancreatic pain varies in severity from mild
(controllable with simple analgesics such as paracetamol (eg
Panadol)) to severe (requiring morphine-like drugs for control).
In addition to the preventive measures listed above, the basic
principle is to use the drug lowest down the analgesic ladder which
controls the pain. Since the pain is often worse at night and since
both body and mind are at their lowest ebb in the early hours of the
morning, the lowest rung of the analgesic ladder may be pethidine
or morphine (eg MST continus tablets). Since the pain is chronic and
severe, there is a fine line between adequate analgesia and
addiction.