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CIRRHOSIS: advanced liver disease
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INTRODUCTION:
Cirrhosis is a chronic liver disease often associated with alcoholism. After
heart disease and cancer, cirrhosis is the third most common cause of death
in people aged 45-65 years. Cirrhosis is a general term for end-stage liver
disease, which can have many causes and which disrupts normal liver tissue.
Cirrhosis has no cure, but removing the ultimate cause can slow the disease.
Findings from several studies, however, have shown interferon alone or
interferon plus ribavirin can be effective for some individuals in slowing,
stopping, and perhaps reversing fibrosis and activity (inflammation &
necrosis of the liver) both for individuals with sustained viral response to
therapy and for some individuals who are non-responders. Patients with a
sustained response were more successful. Here are links to 3 such studies
presented at the AALSD annual liver conference in November 2001 and a
published article. These findings are encouraging but we need more studies to
confirm these findings, to better understand these study results, and to
study the clinical outcomes for the patients.
EFFECT OF INTERFERON AND RIBAVIRIN ON PROGRESSION OF LIVER FIBROSIS IN
PATIENTS WITH SEVERE CHRONIC HEPATITIS C
http://www.natap.org/2001/aasld2/day25.htm
Impact of Pegylated Interferon alfa-2b (Peg-Intron) and Ribavirin on
Progression of Liver Fibrosis in patients with Chronic Hepatitis C
http://www.natap.org/2001/aasld2/day21.htm
In this study Thierry Poynard examined 3000 patients and 5000 paired biopsies
20 months apart from 10 studies using interferon, PegIntron and ribavirin.
Non-responders and responders improved or stabilized their activity score
their Metavir fibrosis score by at least 1 stage. Poynard reported that some
patients with stage 2, 3, and 4 fibrosis stage who were non-responders
stopped disease progression and some sustained responders experienced a
dramatic decrease or reversal in fibrosis rate. In what Poynard called
surprising, he found half of the patients with cirrhosis who had paired
biopsies reversed fibrosis: 33% of sustained responders & 15% of
nonresponders.
Can Cirrhotics Achieve a Histologic Response?
http://www.natap.org/2001/sep/can_cirrhotics090401.htm
In this study Jenny Heathcote did paired biopsies of cirrhotic patients who
received Pegasys monotherapy, and used the Histologic Activity Index which
combines both inflammation and fibrosis into one score to evaluate
improvements in histology. A high percentage of sustained responders achieved
a histologic response and 35% receiving Pegasys alone had a histologic
improvement.
In cirrhosis, the liver responds to cell injury and death by producing
strands of scar tissue that surround islands (nodules) of healing cells,
making the liver knobby. The liver may be injured by a single event (acute
hepatitis), over months or years (biliary tract blockage or chronic
hepatitis), or continuously (alcohol abuse). The knobs, or nodules, and scar
tissue can compress veins within the liver, resulting in high liver blood
pressure (portal hypertension).
The scar tissue hinders the liver's ability to perform its normal functions,
such as clearing toxins, forming proteins, and storing energy. Other problems
may result.
Portal hypertension: High pressures within blood vessels of the liver occur
in 60% of people who have cirrhosis. Cirrhosis is the most common cause of
portal hypertension in the United States. You may suffer from bleeding into
the intestines and fluid accumulation throughout your body.
Hepatic encephalopathy: In this condition, toxins build up in your
bloodstream because your scarred liver is unable to rid them from your body.
The toxins can cause you to behave bizarrely, to become confused, and to no
longer be able to take care of yourself or others.
Gastrointestinal bleeding: Portal hypertension causes bleeding from
varicose veins in your esophagus, which can be life threatening.
Infection: Fluid can accumulate in your abdomen and become infected. If you
have cirrhosis, you are at risk for many infections because your liver cannot
form the proteins needed to fight off infection.
Fluid (ascites): High pressures (portal hypertension) force fluid out of
blood vessels in your liver, pooling it in your abdomen. Several liters of
blood can pool in your abdomen, causing pain, swelling, difficulty breathing,
and dehydration.
Fluid retention: As fluid pools in your abdomen, your kidneys will try to
hold onto more water, because they think your body is dehydrated. The excess
fluid collects in your lungs, legs, and abdomen.
CAUSES:
Cirrhosis can be caused by a number of conditions, including long-standing
inflammation, poisons, infections, and heart disease. In the US, alcoholism
most often causes the disease, followed by hepatitis, usually a viral
infection of the liver. However, for 30-50% of cirrhosis cases, no cause can
be found.
Alcoholic cirrhosis: Alcohol can poison all living cells and cause your
liver cells to become inflamed and die. Their death leads your body to form
scar tissue around veins of your liver. Healing liver cells (nodules) also
form and press on the liver veins. This scarring process occurs in 10-20% of
alcoholics and is the most common form of cirrhosis in the US. The process
depends on how much you drink and how long you have been abusing alcohol.
Some families may have more risk of this type of cirrhosis than others.
Postnecrotic cirrhosis: Hepatitis, a viral infection of the liver, usually
causes this disease, although poisonous substances may also cause it. Two
types of hepatitis, hepatitis B or hepatitis C, cause 25-75% of these cases.
Large areas of scar tissue mix with large areas of healing nodules.
Biliary cirrhosis: When small tubes that help you digest food become
blocked, your body mistakenly turns on itself and reacts against these bile
tubes. Gallstones often block tubes and cause this type of cirrhosis. The
disease usually affects women aged 35-60 years.
Cardiac cirrhosis:Your heart is a pump that pushes blood throughout your
body. When your heart doesn't pump well, blood "backs up" into the liver.
This congestion causes damage to your liver. It may become swollen and
painful. Later it becomes hard and less painful. The cause of the heart
failure may be from heart valve problems, smoking, or infection of the heart
muscle or the sac around the heart.
SIGNS AND SYMPTOMS:
Your doctor may ask you about alcohol abuse, hepatitis, poisonous exposures,
blood transfusions, or IV drug abuse.
You may complain of nausea, weight loss or gain, fluid overload, feeling
weak and tired, and loss of sex drive.
Your skin and eyes may turn yellow (a condition called jaundice).
You might have fever, abdominal swelling or pain, difficulty breathing,
vomiting, diarrhea, bleeding from gums or nose, blood in your vomit or feces,
and abnormal menstrual periods.
Other symptoms include loss of muscle mass, ankle swelling, confusion
(hepatic encephalopathy), and hemorrhoids. Men might notice enlargement of
the breasts (gynecomastia), scrotal swelling, or small testes.
HOME CARE:
You must stop drinking alcohol. If you stop all alcohol intake, you may
slow the disease and feel better.
Ask your doctor what medications you should avoid that may be harmful to
your liver.
Begin a low-sodium diet if you are having problems with fluid retention.
Eat a balanced diet with adequate calories and protein. You also may want
to take a daily multivitamin if your doctor agrees.
If you ever have developed any brain disorder caused by your liver (hepatic
encephalopathy), you should decrease your protein intake.
WHEN TO CALL THE DOCTOR;
Sudden weight changes
Increasing water retention
Yellow skin (jaundice)
WHEN TO GO TO THE HOSPITAL:
Blood in your vomit or stool
Difficulty breathing
Abdominal pain
Confusion or bizarre behavior
Repeated vomiting
Fever
PHYSCIAN DIAGNOSIS:
Your doctor may suspect cirrhosis if you have a history of alcohol abuse, IV
drug use, or hepatitis, or if you have bleeding, jaundice, ascites (water
building up in your abdomen), or any brain disorder.
You may be diagnosed with cirrhosis after its complications develop. Usually
your doctor can make a diagnosis based on your history and physical exam
alone. But taking a biopsy‹removing tissue from the liver and studying it
under a microscope‹remains the only way diagnosis can be 100% certain.
The doctor may collect blood to look for problems with your electrolytes,
blood count, clotting ability, or your liver and kidney function. Often
routine blood tests may appear normal, however.
PHYSCIAN TREATMENT:
Many medicines have been studied, such as steroids penicillamine
(Cuprimine, Depen) and an anti-inflammatory agent (colchicine), but they have
not been shown to improve survival. Most treatment for cirrhosis is directed
toward relief of complications.
Various surgeries can be performed to redirect liver blood flow into the
circulatory system, reducing liver blood pressures. However, surgery may
worsen hepatic encephalopathy or ascites. No surgery has been proven to
improve long-term survival.
Intestinal bleeding requires hospitalization because you are at high risk
of bleeding to death. You have a 1 in 2 chance of dying during that hospital
stay if you suffer from bleeding varicose veins in your esophagus.
If you have significant blood loss, you will need oxygen, close
monitoring, and 2 large IV lines to restore lost fluids.
You may need blood transfusions.
Doctors diagnose ongoing bleeding from the esophagus by inserting
a tube down your nose into your stomach to suck out any pooled blood. Once
they recognize bleeding, various methods can control it.
Balloon inflation to compress the vein
Medications that decrease blood flow into the liver
Tying off the bleeding vein
Ascites, the build-up of water in your abdomen, will be treated.
Your doctor may prescribe diuretics (water pills)‹medicines that
make you urinate more often.
Your doctor may insert a needle into your abdomen to directly
remove large amounts of fluid. However, the fluid usually collects again.
If the fluid becomes infected, you will be hospitalized and given IV
antibiotics.
If you have significant hepatic encephalopathy, you will be hos
pitalized, particularly if you have become so confused you cannot care for
yourself.
You will be given lactulose, a drink that reduces the
amounts of toxins absorbed into your intestinal tract.
You may be started on a low-protein diet.
Combining these 2 treatments improves symptoms in 75% of
cases.
You might be sent home and instructed to take lactulose
every day and change to a low protein diet, but to return if symptoms come
back.
Clotting disorders: Adequate protein intake and vitamin supplements can
help to correct clotting disorders caused by the inability of your liver to
form clotting factors.
Hepatorenal syndrome: For unknown reasons, liver failure sometimes leads to
kidney failure. Without a liver transplant, kidney failure usually is fatal,
often causing several organs throughout the body to fail.
Cancer: People often develop liver cancer before they develop
cirrhosis. You may die within 3-6 months after diagnosis if the cancer
remains untreated. Even with treatment, people rarely survive beyond 5 years.
Surgery is the only chance for a cure, but usually the cancer has
progressed too far by the time surgery is performed.
Liver transplantation may also be considered.
Researchers are studying various experimental treatments, such as
chemoembolization, alcohol ablation, cryoablation, immunotherapy, and gene
therapy.
PROGNOSIS:
Your recovery depends on the type of cirrhosis you have and if you stop
drinking. Only 50% of people with severe alcoholic cirrhosis survive 2 years,
and only 35% survive 5 years. Recovery rate worsens after the onset of
complications (such as gastrointestinal bleeding, ascites, encephalopathy).
As discussed at the beginning of the article interferon plus ribavirin
therapy has been shown to be effective for some patients with HCV-related
cirrhosis. Liver transplantation remains the best treatment, but livers are
available for very few people.
PREVENTION:
Avoid risky behaviors such as alcohol abuse, IV drug use, and unprotected
sexual intercourse.
Hepatitis B immunizations are available to health care workers and others
at high risk of contacting the disease.
Immunization of all American children against hepatitis B, now required,
will reduce the incidence of cirrhosis in the future.
No effective hepatitis C vaccination is available.
FOLLOW UP:
You must be hospitalized for further work-up and treatment if you are
diagnosed with cirrhosis after having a major complication.
If you have liver disease but no major complications, you may undergo a
work-up as an outpatient if the following criteria are met:
You have no signs or symptoms of infection.
Your blood still has the ability to form clots adequately.
You have close follow-up arranged (within 2 days) with your doctor.
You are able to hold down foods and liquids.
You will be in the company of an adult who can recognize complications and
seek help should you become confused and unable to care for yourself.
BIBLIOGRAPHY:
American Medical Association Staff, ed: AMA Drug Evaluations Annual.
10th ed. United States Pharmacopeia; 1994.
Butterworth RF: Complications of cirrhosis III. Hepatic encephalopathy.
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Cline DM, Allison EJ, Jr: Hepatic failure and cirrhosis. In:
Harwood-Nuss, ed. The Clinical Practice of Emergency Medicine. 1996: 698-703.
Crawford JM: The gastrointestinal tract: liver, biliary tract, and
pancreas. In: Robbins SL, Cotran RS, Kumar V, eds. Robbins Pathologic Basis
of Disease, 4th ed. Philadelphia: W.B. Saunders Co., 1991.
Guss DA: Disorders of the liver, biliary tract, and pancreas. In: Rosen
P, ed. Emergency Medicine: Concepts and Clinical Practice. 14th ed. Mosby;
1998: 1981-2005.
Hadziyannis SJ: Why and how to treat chronic hepatitis C. Can J
Gastroenterol 2000 Jul-Aug; 14 Suppl B: 45B-48B[Medline].
Podolsky KP, Isselbacher KJ: Alcohol-related liver disease and
cirrhosis. In: Harrison's Principles of Internal Medicine. 13th ed.
McGraw-Hill; 1994: 1483-1495.
Rikkers LF: Surgical complications of cirrhosis and portal
hypertension. In: Sabiston, DC, ed. Textbook of Surgery. Philadelphia: WB
Saunders Co; 1992.
Vlachogiannakos J, Goulis J, Patch D, et al: Review article: primary
prophylaxis for portal hypertensive bleeding in cirrhosis. Aliment Pharmacol
Ther 2000 Jul; 14(7): 851-60[Medline].
Wallace S, Kan Z, Li C: Hepatic chemoembolization: clinical and
experimental correlation. Acta Gastroenterol Belg 2000 Apr-Jun; 63(2):
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Medicine is a constantly changing science and not all therapies are clearly
established. New research changes drug and treatment therapies daily. The
authors, editors, and publisher of this journal have used their best efforts
to provide information that is up-to-date and accurate and is generally
accepted within medical standards at the time of publication. However, as
medical science is constantly changing and human error is always possible,
the authors, editors, and publisher or any other party involved with the
publication of this article do not warrant the information in this article is
accurate or complete, nor are they responsible for omissions or errors in the
article or for the results of using this information. The reader should
confirm the information in this article from other sources prior to use. In
particular, all drug doses, indications, and contraindications should be
confirmed in the package insert
Author: Jeffrey A Gunter, MD, Staff Physician, Department of Surgery,
Division of Emergency Medicine, Denver Health Medical Center
Coauthor(s): Erik D Barton, MD, MS, Associate Director, Assistant Professor,
Department of Surgery, Division of Emergency Medicine, University of Utah
Health Sciences Center
Jeffrey A Gunter, MD, is a member of the following medical societies: Alpha
Omega Alpha, American College of Emergency Physicians, American Medical
Association, Association of American Physicians and Surgeons, and Texas
Medical Association
Editor(s): Scott H Plantz, MD, FAAEM, Research Director, Assistant Professor,
Department of Emergency Medicine, Mount Sinai School of Medicine; Francisco
Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; John A Calomeni,
MD, JD, Consulting Staff, Department of Emergency Medicine, Seton Medical
Center; Jonathan Adler, MD, Instructor, Department of Emergency Medicine,
Massachusetts General Hospital, Harvard Medical School; and Steven L
Bernstein, MD, Vice-Chair, Academic Affairs, Department of Emergency
Medicine, Newark Beth Israel Medical Center; Assistant Professor, Department
of Emergency Medicine, Mt Sinai School of Medicine
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