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LIVER
CIRRHOSIS
The Liver
The liver is the
largest organ (about the size of a football and averaging
about 3.5 pounds) and has more functions than any other human
organ. A person's entire blood supply passes through the liver
several times a day, and at any given time there is about a
pint of blood there. The liver produces and secretes bile (to
be stored in the gallbladder until needed) that is used to
break down and digest fatty acids. It also produces
prothrombin and fibrinogen, both blood-clotting factors, and
heparin, a mucopolysaccharide sulfuric acid ester that helps
keep blood from clotting within the circulatory system.
The liver converts
sugar into glycogen, which it stores until the muscles need
energy and it is secreted into the blood stream as glucose.
The liver synthesizes proteins and cholesterol and converts
carbohydrates and proteins into fats, which are stored for
later use. It also produces blood protein and hundreds of
enzymes needed for digestion and other bodily functions. As it
breaks down proteins, the liver also produces urea, which it
synthesizes from carbon dioxide and ammonia. (Urea, the
primary solid component of urine, is eventually excreted by
the kidneys.) The liver also stores critical trace elements
such as iron and copper, as well as vitamins A, D, and B12.
Cirrhosis
Cirrhosis of the liver
is a chronic, diffuse (widely spread throughout the organ),
degenerative liver disease in which the parenchyma (the
functional organ tissue) degenerates, the lobules are
infiltrated with fat and structurally altered, dense
perilobular connective tissue forms, and areas of regeneration
often develop. The first scientist known to have diagnosed the
disease was Gianbattista Morgagni, who published 500 autopsies
in 1761. Laennec named the disease in 1826, using the Greek
word for orange color because cirrhotic livers turn a
yellowish to tan color.
Cirrhosis is the
seventh leading cause of death by disease in the United
States, with about 25,000 dying from it each year (down from
50,000 in 1979). About a third of the cases are compensated,
meaning there are no clinical symptoms. Such cases are usually
discovered during routine tests for other problems, or during
surgery or autopsy. In most cases, though, there is a loss of
liver cell function, and an increased resistance to blood flow
through the damaged liver tissue (a condition known as portal
hypertension) leading to esophageal varices (enlarged, swollen
veins at the lower end of the esophagus). Severe cirrhosis
leads to ammonia toxicity, hepatic coma, gastrointestinal
hemorrhage, and kidney failure. As liver cells are destroyed,
they are systematically replaced by scar tissue.
Symptoms
Symptoms of cirrhosis
include nausea or indigestion and vomiting, constipation or
diarrhea, flatulence, anorexia, weight loss, ascites (the
accumulation of serous fluids in the peritoneal cavity),
light-colored stools, weakness or chronic dyspepsia, dull
abdominal aching, varicosities, nosebleeds, bleeding gums,
other internal and external bleeding, easy bruising, extreme
dryness of skin, and spider angiomas. Psychotic mental changes
such as extreme paranoia can occur in cases of advanced
cirrhosis. Other symptoms are testicular atrophy, gynecomastia
(enlargement of the male breast), and loss of chest and armpit
hair.
Complications
When blood flow in the
cirrhotic liver is restricted, blood can "back up"
in the spleen, causing enlarged spleen and sequestered blood
cells. In this condition the platelet count typically falls,
and abnormal bleeding can result. In extreme cases blood can
actually flow backward from portal circulation to systemic
circulation, leading to varicose veins in the stomach (gastric
varices), esophagus (esophageal varices), and rectum
(hemorrhoids). Ruptured varices bleed massively and are often
fatal. Bilirubin levels may build up in the blood, causing
jaundice and bright yellow to dark brown urine. Cirrhosis can
also cause insulin resistance and diabetes mellitus. Brain
injury can result from inadequate filtering of blood toxins.
Such brain damage can have symptoms that range from poor
concentration to coma, swelling of the brain, stupor, and even
death. Cirrhosis is often associated with osteomalacia (the
adult form of rickets, a softening of the bones that often
leaves them brittle) and osteoporosis (a reduction in bone
mass).
The Alcohol
Factor
The most common cause
of cirrhosis is believed to be alcohol (ethanol) abuse (about
10% of American men and about 3% of American women chronically
abuse alcohol). Though it affects many organs, alcohol is
especially harmful to the central nervous system and the
liver, and is a factor in about three-fourths of the cases of
cirrhosis in the United States. Alcohol must be metabolized,
and the liver performs most of that job, suffering serious
damage in the process. Not only does alcohol destroy liver
cells, it also robs them of their ability to regenerate.
Such cofactors as
hepatitis C virus can increase the risk of cirrhosis in those
whose intake of alcohol is excessive. Alcohol-induced
cirrhosis is among the ten leading causes of death in the
United States. Women are at much higher risk for
drinking-related cirrhosis than are men. This may be true
because less of the alcohol consumed is metabolized in the
stomach in women before being absorbed into the blood stream.
Autopsies indicate that from 10 to 15% of American alcoholics
suffer from cirrhosis at the time of death. About a third of
those consuming one cup to one pint (8 to 16 ounces) of hard
liquor a day (or the equivalent in other drinks) over a
15-year period will develop cirrhosis.
In addition to
cirrhosis, alcohol abuse can lead to fatty liver, which can
lead to stearohepatitis (or steatohepatitis, the older term),
scarring of the liver, and eventually to cirrhosis. Overuse of
alcohol can also lead to acute, chronic hepatitis.
Complications can include liver dysfunction, abnormal blood
clotting, jaundice, and hepatic encephalopathy (neurological
dysfunction brought on by failure of the liver). Chronic
abusers of alcohol often need significant vitamin
supplementation to correct vitamin deficiencies caused as much
by neglect and poor eating habits as by damage from the
alcohol. An acute thiamin (vitamin B1) deficiency is typical.
Other Risk
Factors and Causes
Cirrhosis patients are
at high risk for obesity, fatal bacterial infections, stomach
ulcers, kidney problems, gallstones, and diabetes mellitus.
They are also at increased risk for liver cancer. Risk factors
for cirrhosis include nutritional deficiencies (lack of
proteins, vitamins, choline, trace elements, or methionine),
hepatitis (B, C, or D) and other bacterial and viral
infections, and severe reactions to prescription or
"recreational" drugs. Vitamin B1 (thiamin)
deficiency may directly cause alcoholic cirrhosis. One study
concluded that vitamin B1 deficiency is a greater risk factor
for liver cell death than heavy alcohol consumption.
Congestive heart
failure and poisons (including alcohol, phosphorus, and carbon
tetrachloride) pose a serious threat to the liver and can lead
to cirrhosis. Genetic disorders, inherited metabolic diseases
such as hemochromatosis (marked by excessive iron absorption
and accumulation) and Wilson's disease (in which the liver
stores too much copper), advanced syphilis, exposure to blood
flukes, other parasitic infections (such as schistosomiasis),
and blocking of the common bile duct are all factors that can
lead to cirrhosis. Liver injury from an accident or from
cystic fibrosis can also bring on cirrhosis.
Diagnosis
Positive diagnosis of
cirrhosis must be made by liver biopsy, but X-ray, blood
tests, and physical examination are all used in diagnosis, as
is observation of the symptoms mentioned earlier. CAT
(computerized axial tomography) scans, radioisotope liver
scans, and ultrasound can all be used to diagnose cirrhosis.
Early diagnosis is critical in order to establish the cause of
the disease and determine the amount of damage to the liver.
Two symptoms of
cirrhosis are the loss of healthy, functioning liver cells and
the scarring and distortion of the liver that eventually take
place. As fewer cells function, less albumin (a protein) is
manufactured. Lowered albumin levels permit water retention
(edema) in the legs and abdomen (ascites). Easy bruising and
bleeding result, and, in some cases, vomiting of blood.
Intense skin itching can also result from excessive bile
product deposits in the skin, often accompanied by jaundice or
yellow skin.
Gallstones are more
likely to form in cirrhosis patients because there is not
enough bile reaching the gallbladder. Toxins that the liver
would normally remove build up in the blood, dulling mental
functions and bringing on personality changes. Drugs the
patient is taking, normally filtered out and disposed of in
urine, may remain in the bloodstream for a much longer period
and act longer than expected or even build up in body tissue.
A liver with cirrhosis is usually much larger than a healthy
liver.
Precautions and
Prevention
Once cirrhosis has been
diagnosed, sodium and fluids should be restricted, and all
alcohol consumption must cease. Antiemetics, diuretics, and
supplemental vitamins are prescribed. Cirrhosis patients
should avoid straining at the bowel, violent sneezing and
coughing, and nose blowing, and should use stool softeners as
prescribed by a qualified medical caregiver. Untreated
cirrhosis can be fatal; patients should avoid exposure to
infections and eat small but frequent meals of nutritious
foods, carefully following caregiver instructions. The liver
is the only organ that can generate healthy, new tissue in
response to injury or disease. It is therefore possible to
regenerate a cirrhosis-damaged liver if extraordinary
therapies are followed and the underlying cause of the
cirrhosis is eliminated.
More than half of all
liver disease could be prevented if we acted on the knowledge
we already have. Avoiding or limiting the use of alcoholic
beverages is a good place to start, because it is well
documented that alcohol destroys liver cells. Man-made
chemicals also pose an extreme threat to the liver, so take
recommended precautions. Remember that all ingested, inhaled,
and absorbed toxins must be processed by the liver. When
working with hazardous chemicals use adequate ventilation;
follow product instructions; do not mix chemicals; wear
protective clothing and breathing equipment; avoid inhalation
and ingestion of hazardous materials; avoid skin contact and
flush (wash) affected areas immediately; if necessary, call
your poison control center or your emergency number (such as
911). A complete listing of toll-free poison control center
numbers can be obtained online at MediciNet.com.
Treatments
When varices result,
they can be treated with a reduction of salt intake and with
diuretics, which help eliminate excess salts and fluids from
the body. Coma and encephalopathy are treated by a reduction
of protein intake, and hemorrhage from varices can be stopped
by sclerotherapy (injection of a scarring chemical into the
bleeding vein). Varices can also be compressed by the use of a
special balloon that is inflated around the enlarged vein,
squeezing it as the balloon is inflated. There is a new
procedure (using radiology)-transjugular intrahepatic
protosystemic shunt (TIPS)-that shows some promise.
Interferon-alpha, a
powerful antiviral, may reduce the risk of cancer in some
cirrhosis patients. In cases of total liver failure,
transplantation has been successful. Over 80% of liver
transplant patients are still alive 5 years after the surgery.
Japanese researchers found evidence that malotilate prevented
both damage to liver cells and cirrhosis they attempted to
induce in rats.
Natural
Therapies
The liver can often
perform its essential functions in spite of serious damage. It
also has more ability to self-repair than do most other
organs. It is important to give the liver the nutrients it
needs to function and to regenerate and detoxify itself.
Research done at the Center for Biomedical Research at the
Hospital of St. Joan in Reus, Spain, in 1992 shows that
supplementation of zinc lessens the effects of fibrogenesis in
rats with induced cirrhosis. German research shows that zinc
deficiencies are implicated in liver cirrhosis and concludes
that zinc substitution should be provided to all cirrhosis
patients when deficiency and corresponding symptoms are found.
(Long-term supplementation of zinc should not exceed 90 mg a
day.) Selenium deficiencies have also been found in the blood
of cirrhosis patients, leading to recommendations for selenium
supplementation. Ursodeoxycholic acid, a widely tested bile
acid, has been found effective in slowing the progress of
cirrhosis, preventing gallstone formation, and preventing the
formation of varices.
Research has shown
decreased blood serum levels of vitamins E and K1, and
increased levels of vitamin A and iron in some cirrhosis
patients. These patients should not directly supplement
vitamin A or beta carotene, and should also avoid niacin
(vitamin B3) and supplements containing extracts from the
chaparral shrub. (Some research found absolutely no
correlation between cirrhosis and vitamin A levels in the
liver and concluded that cirrhosis patients were not at
increased risk from vitamin A supplementation, while other
studies showed decreased vitamin A levels in cirrhosis
patients. More research is needed, but cirrhosis patients
should consider vitamin A supplementation only under direct
medical supervision.) Japanese studies showed that moderate
intake of caffeine (in coffee) helped to counteract some of
the negative effects of alcohol on the liver. Consumption of
caffeine in green tea showed no such effect.
In Russian studies,
supplementation with ascorbic acid (vitamin C) and alpha-tocopherol
(vitamin E) improved the liver function of chronic liver
disease patients. In a 1998 American study it was found that a
high level of supplementation of vitamins B2 (riboflavin) and
B12 (cyanocobalamin and hydroxycobalamin, associated with
folate metabolism) reduced the risk of cirrhosis associated
with alcohol consumption above 50 grams (1.75 ounces) a day.
Recommended supplements
for a seriously damaged liver are the amino acids acetyl-L-carnitine
(2000 mg a day), N-acetylcysteine (600 mg twice a
day), L-arginine (5 to 10 grams a day), leucine (1200
mg a day), isoleucine (600 mg a day), and valine (600 mg a
day). Silymarin (at about 600 mg a day) is effective in
cirrhosis patients, even in alcoholic liver cirrhosis. It is
especially helpful for diabetics with cirrhosis because it
reduces the lipoperoxidation of cell membranes and insulin
resistance, decreasing the need for insulin supplementation. L-Arginine
(up to 5 to 10 grams a day) and glutamine (2000 mg a day) are
only effective when there is still at least 20% liver function
remaining. (L-arginine should be taken under a
doctor's supervision.)
Because ethanol damages
the liver at least in part by the generation of free radicals,
and because it depresses an enzyme needed to convert
methionine into SAMe (S-adenosylmethionine), SAMe
supplementation can help regenerate normal liver function.
Periodic blood testing is required to monitor the
effectiveness of patient therapy. Doses of 400 to 800 mg twice
a day have shown promise in reversing alcoholic cirrhosis. A
less expensive alternative is twice-a-day supplementation with
500 mg of TMG (trimethylglycine, or betaine), folic acid (800
mcg), and vitamin B12 (500 mcg per day). Supplementation with
phosphatidylcholine (2000 mg per day) may provide protection
against alcohol-induced septal fibrosis, cirrhosis, and lipid
peroxidation.
Because anemia is a
common complication in cirrhosis patients, iron deficiency is
a possibility. Iron supplementation should only be used under
direct medical supervision with close monitoring because
excessive iron can cause severe liver damage, especially when
combined with alcohol, porphyrogenic drugs, or chronic viral
hepatitis. Iron can also enhance the disease-producing
abilities of viruses, adversely affect immune function, and
enhance fibrogenic pathways, all of which may increase liver
injury. Iron may also be implicated as a cocarcinogen or
promoter of hepatocellular carcinoma, even in patients without
hepatitis C or cirrhosis.
Ongoing
Research
There is a large amount
of research and study into causes and cures of cirrhosis of
the liver. Patients and healthcare providers should stay
abreast of research findings for the latest developments in
cirrhosis treatment and therapy.
Summary
Cirrhosis of the liver can be caused by excessive alcohol
consumption, accidental, bacterial, or viral liver damage,
exposure to toxic chemicals, and severe reaction to
prescription or "recreational" drugs.
Supplementation of antioxidants, branched chain amino acids,
and all except B3 (niacin) of the B complex of vitamins has
been shown to be beneficial. For specific antiviral therapies
to help eradicate hepatitis B or C, refer to our Hepatitis B and Hepatitis
C protocols.
- Drink alcohol in moderation if at all. If diagnosed with
cirrhosis, do not drink.
- Studies on alcoholic cirrhosis patients have shown benefits from
supplementing valine, leucine, and isoleucine. These
branched-chain amino acids can enhance protein synthesis
in liver and muscle cells and are used by body builders to
produce an anabolic effect. Four capsules of Branch Chain
Amino Acids (free form) provide 200 mg of L-leucine,
600 mg of L-isoleucine, 600 mg of L-valine,
and 10 mg of vitamin B6 (pyridoxine). The suggested dose
is 2 to 4 capsules per day between meals with fruit juice
or before eating.
WARNING:
These capsules are only to be used by adults who are fully
grown, and not by anyone afflicted with pellagra.
- Patients with depleted SAMe levels should take from two to four
200-mg tablets a day of SAMe, spread throughout the day.
Patients must adhere to physician-prescribed blood testing
schedules to assess the effectiveness of this therapy. A
cost-effective alternative to SAMe supplementation is TMG
(trimethylglycine). The suggested dose is two 500-mg
tablets after meals, twice a day, or as directed by a
physician.
- The vitamin B complex is extremely important for liver health.
Therefore, daily supplementation of vitamins B1 (500 mg),
B2 (75 mg), B5 (1500 mg), and B6 (200 mg) is strongly
recommended (though vitamin B3 [niacin] should be avoided
by cirrhosis patients).
- Other recommended daily supplements are 1500 mg of choline, 1600
mg of folic acid, 500 mg of vitamin C, 800 IU of vitamin
E, 300 micrograms of selenium, and 100 mg of coenzyme Q10
(for its antioxidant and blood flow-enhancing properties).
- 5. Acetyl-L-carnitine should be taken in two daily
doses of 1000 mg each. Take two 600 mg doses per day of N-acetylcysteine.
Drink green tea, or take 4 to 10 standardized 100 mg
capsules of green tea extract a day to lower toxic levels
of iron (which may exacerbate free radical damage to the
liver).
- 5 to 10 grams of L-arginine and 2000 mg a day of
glutamine may help lower blood levels of toxic ammonia
permitted to build up by a damaged liver. L-arginine
can help facilitate liver regeneration if the liver still
has at least 20% functional reserve capacity.
- Silymarin treatment (about 600 mg a day) is appropriate for all
alcoholic liver disease patients, and has reduced insulin
resistance in diabetic patients with cirrhosis.
- Zinc should be supplemented in cirrhosis patients at a rate of
at least 30 mg per day (not to exceed 90 mg a day), while
selenium should be supplemented according to your doctor's
instructions.
For
more information.
Contact the American Liver Foundation, (800) 223-0179.
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