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Cirrhosis
†Cirrhosis is a disease which involves irreversible scarring of the liver.
†Alcohol, viral hepatitis B and C are common causes of cirrhosis, although
there are many other causes.
†Cirrhosis can cause yellowing of the skin (jaundice), itching, and fatigue.
†Diagnosis of cirrhosis can be suggested by physical examination and blood
tests, and can be confirmed by liver biopsy in some patients.
†Complications of cirrhosis include mental confusion, coma, fluid accumulation
(ascites), internal bleeding, and kidney failure.
†Treatment of cirrhosis is designed to limit any further damage to the
liver as well as complications.
†Liver tansplantation is becoming an important option for patients with
advanced cirrhosis.
What is cirrhosis?
Cirrhosis refers to a disease of the liver in which normal cells are replaced
by scar tissue. This condition results in the failure of the liver to perform
many of its usual functions. The liver has many functions which include the
production of proteins and enzymes. It also is involved in the regulation of
cholesterol and storage of energy. The loss of normal liver function in cirrhosis
leads to abnormalities in the liver's ability to handle drugs and toxins. The
loss of normal liver structure in cirrhosis also interferes with the normal
flow of blood through the liver. Complications resulting from cirrhosis can
be serious. These include internal bleeding, kidney failure, mental confusion,
coma, body fluid accumulation, and frequent infections.
What are the major causes of cirrhosis?
There are many causes of cirrhosis. Alcohol is a very common cause, particularly
in the Western world. The development of cirrhosis in alcohol consumers depends
upon the amount and regularity of intake. Those individuals who drink at least
eight to sixteen ounces of hard liquor or the equivalent daily for fifteen or
more years will develop cirrhosis thirty percent of the time.
Viral liver disease is also a common cause of cirrhosis, although most patients
with viral hepatitis will not develop cirrhosis. Hepatitis B and C are the most
common viral liver diseases associated with cirrhosis. On the other hand, hepatitis
A has never been reported to cause chronic liver disease or cirrhosis.
Many inherited disorders result in the accumulation of toxic substances in the
liver which lead to tissue damage and cirrhosis. Examples include the abnormal
accumulation of iron (hemochromatosis) or copper (Wilson's disease). In hemochromatosis,
patients inherit a tendency to absorb an excessive amount of iron from food.
Over time, iron accumulation in different organs causes cirrhosis, arthritis,
heart muscle damage leading to heart failure, and testicular dysfunction causing
loss of sex drive. Treatment involves prevention of organ damage by removing
iron from the body through bloodletting. Interestingly, menstruation protects
women from organ damage until after menopause. In Wilson' disease, the inherited
abnormality is in the protein that handles copper. Over time, copper accumulates
in the liver, eyes, and brain. Cirrhosis, tremor, psychiatric disturbances and
other neurological difficulties occur if the condition is not treated early.
Treatment involves oral medication to increase copper excretion in the urine.
Primary biliary cirrhosis (PBC) is a liver disease caused by an abnormality
of the immune system found predominantly in women. Normally, bile produced by
the liver is delivered through the bile ducts to the intestines to digest fat.
In PBC, the small bile ducts within the liver become inflamed and obliterated.
Backup of bile contents causes intense skin itching and subsequent yellowing
of the skin (jaundice). Lack of bile also decreases absorption of calcium and
vitamin D, leading to an eventual thinning of the bones. Over time,cirrhosis
develops and liver transplantation is considered.
Primary sclerosing cholangitis (PSC) is a rare condition found in association
with ulcerative colitis (see ulcerative colitis). In PSC, the large bile ducts
outside the liver become inflamed and obstructed. Obstruction of bile leads
to frequent infections and jaundice and eventually causes cirrhosis and the
need for liver transplantation. In some patients, injury (usually result of
surgery) to the bile ducts can cause obstruction and cirrhosis of the liver.
Autoimmune hepatitis is found more commonly in women. For unknown reasons, the
body unleashes its immune system against its own liver. Treatment involves medications
such as corticosteroids to suppress the immune system.
Babies can be born without bile ducts (biliary atresia), leading to cirrhosis.
Others are born without certain vital enzymes, leading to the accumulation of
sugars which may also cause cirrhosis of the liver. On rare occasions, the absence
of certain specific enzymes can lead to liver as well as lung injury, as in
alpha 1 antitrypsin deficiency.
Less common causes of cirrhosis include unusual reactions to certain drugs,
prolonged exposure to toxins, as well as chronic heart failure (cardiac cirrhosis).
In certain parts of the world (particularly Northern Africa), infection of the
liver with a parasite (schistosomiasis), which causes cirrhosis, is the most
common cause of all liver disease.
What are the symptoms of cirrhosis?
Most patients with cirrhosis have few symptoms. Cirrhosis may be suggested by
yellowing of the skin (jaundice). Non-specific symptoms such as fatigue, weakness
and loss of appetite may occur. Itching results from the back up of bile into
the blood and skin. Easy bruising can result from a decreased production of
clotting proteins by the diseased liver.
Fluid can accumulate in the abdominal cavity (ascites) and legs (edema) as a
result of the obstruction of blood flow through the liver. This is further complicated
by decreased protein production by the cirrhotic liver. The fluid can become
infected (spontaneous bacterial peritonitis) and can be life threatening. More
often, the fluid causes abdominal discomfort and weight gain.
Because blood flow through the liver is slowed in cirrhosis, blood returning
from the intestine back to the heart must find alternative channels. This often
leads to the engorgement of varicose-like veins (varices) in the esophagus and
stomach. These thin-walled veins can rupture under high pressure and cause internal
hemorrhage. This can result in vomiting of blood, passing of black tarry stools,
and even shock.
The liver of a patient with cirrhosis also poorly filters toxins (like ammonia)
that can accumulate in the blood. This can lead to confusion or personality
changes (encephalopathy). Forgetfulness, loss of concentration, confusion, and
poor sleeping habits may be a consequence. When this condition becomes severe,
loss of consciousness (coma) and impaired breathing can develop. Patients are
also very sensitive to medications that are normally filtered by the liver.
This is especially true of sedatives and sleeping medications.
Kidney failure frequently accompanies liver failure. Urine production is markedly
diminished as cirrhosis worsens. In end-stage cirrhosis, complete kidney shut
down (hepato-renal syndrome) is usually fatal.
How is the diagnosis of cirrhosis made?
The diagnosis of cirrhosis may be indicated by a physical examination and laboratory
studies. The liver may be enlarged. Small red spider-like markings (telangiectasias)
may be seen on the skin, particularly on the chest. Yellowness of the skin (jaundice)
and in the whites of the eyes can be seen. Blood tests often reveal decreased
blood proteins, elevated bilirubin, abnormal levels of liver enzymes, and diminished
clotting factors. Special viral tests may implicate viral infection as the cause
of cirrhosis. Elevated iron levels in the blood suggest the possibility of hemochromatosis.
Diminished levels of ceruloplasmin in the blood suggest abnormality in handling
copper, and hence Wilson's disease. The presence of abnormal antibodies (antinuclear
antibody, anti-smooth muscle antibody) in the blood, suggests autoimmune hepatitis.
In certain circumstances, an x-ray test may be ordered to see the liver. Confirmation
of the diagnosis may be made by obtaining a piece of the liver (biopsy) which
can be examined under a microscope. This is a procedure whereby a needle is
placed through the skin directly into the liver to obtain a liver sample.
What are the treatments for cirrhosis?
Once scarring of the liver occurs, it is permanent. The treatment of cirrhosis
is designed to limit any further damage to the liver as well as any complications.
A good diet and supplemental vitamins may help. Any drugs, including alcohol,
that can lead to additional liver damage should be avoided. If a virus is found
to be responsible for the liver damage, possible anti-viral treatment may be
indicated. Interferon can be helpful when the cause of the disease is hepatitis
B or C and the condition is not severely advanced. In cirrhosis related to the
overload of certain metals, the metal burden in the body can be diminished by
bloodletting (as in hemochromatosis) or medications to cause increased urine
excretion (as in Wilson's disease). Medications that suppress immunity such
as prednisone and azathioprine (IMMURAN) are used in autoimmune hepatitis.
The tendency to retain fluid in cirrhosis can often be managed with restrictions
of fluid and salt intake. Sometimes, medication that increases urine production
(diuretics) may be used to reduce ascites and edema. Itching can sometimes be
improved with cholestyramine (QUESTRAN), a medicine that binds bile. When mental
function impairment results from severe liver damage, dietary restriction of
protein and the use of lactulose, which binds toxins in the intestines can help.
Bleeding from the veins into the esophagus can be treated by infusing sclerosing
agents that work by scarring the veins closed (sclerotherapy). These agents
are administered through a flexible tube which is visually placed through the
mouth into the esophagus. Frequently several sessions are necessary to obliterate
all the veins. When bleeding is uncontrollable, surgery may be necessary. This
involves the creation of a bypass (shunt) to redirect blood away from the liver.
Unfortunately, mental confusion can result although bleeding is controlled.
More recently, non-surgical methods have emerged which allow the creation of
a bypass through the liver that can be done through the veins in the neck. This
procedure has also been successful in the management of severe fluid overload
which also complicates cirrhosis.
When cirrhosis is far advanced, liver transplantation might be considered. Recent
advances transplantation surgery, and medications to prevent infection and graft
rejection have significantly improved survival. On average, over eighty percent
of recipients are alive after five years. In addition, newer medications have
allowed for a higher quality of life, with most patients returning to their
previous work.
What are the future goals in cirrhosis research?
Progress in the management and prevention of cirrhosis continues. Research is
ongoing to determine the mechanism of scar formation in the liver, and how this
process can be interrupted. Newer and better treatments for viral liver disease
are being developed with improved guidelines regarding their indications. Better
understanding of the complications of cirrhosis may lead to improved treatments.
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