Professional Documents
Culture Documents
John J OLeary
Learning objectives
What is cirrhosis?
What is the pathobiology of cirrhosis
What causes cirrhosis
What laboratory investigations are used in diagnosis
and assessment of cirrhosis
What other investigations are used
Treatment
Macronodular cirrhosis
Micronodular cirrhosis
CAUSES OF CIRRHOSIS
Cirrhosis is most commonly caused by:
- Alcohol
- Hepatitis B and C
- Fatty liver disease
- cryptogenic, i.e. of unknown cause
CIRRHOSIS STATISTICS
- Cirrhosis and chronic liver disease were the 10th leading cause of
death for men and the 12th for women in the United States in 2001,
killing about 27,000 people each year.
-Established cirrhosis has a 10-year mortality of 34-66%, largely
dependent on the cause of the cirrhosis.
- The risk of death due to all causes is increased twelvefold; if one
excludes the direct consequences of the liver disease, there is still a
fivefold increased risk of death in all disease categories.
- Little is known on modulators of cirrhosis risk, apart from other
diseases that cause liver injury (such as the combination of alcoholic
liver disease and chronic viral hepatitis, which may act synergistically in
leading to cirrhosis).
- Studies have recently suggested that coffee consumption may protect
against cirrhosis, especially alcoholic cirrhosis.
Gynaecomastia
Hypogonadism
Hepatomegaly
Splenomegaly
Oesophageal varices
Multi-system effects:
Cirrhosis can cause immune system dysfunction, leading to infection.
Fluid in the abdomen (ascites) may become infected with bacteria
normally present in the intestines (spontaneous bacterial peritonitis).
Hepatorenal syndrome - insufficient blood supply to the kidneys,
causing acute renal failure. This complication has a very high mortality
(over 50%).
Hepatopulmonary syndrome - blood bypassing the normal lung
circulation (shunting), leading to cyanosis and dyspnoea (shortness of
breath), characteristically worse on sitting up.
Portopulmonary hypertension - increased blood pressure over the
lungs as a consequence of portal hypertension.[6]
Chronic hepatitis C.
- low grade damage to the liver that over several decades can lead to
cirrhosis.
Chronic hepatitis B.
-The hepatitis B virus is probably the most common cause of cirrhosis
worldwide, especially South-East Asia, but it is less common in the United
States and the Western world.
- Hepatitis B causes liver inflammation and injury that over several
decades can lead to cirrhosis.
- Hepatitis D is dependent on the presence of hepatitis B, but accelerates
cirrhosis in co-infection.
Autoimmune hepatitis:
-This disease is caused by the immunologic damage to the liver causing
inflammation and eventually scarring and cirrhosis.
- Findings include elevations in serum globulins, especially gamma
globulins.
- Therapy with prednisone +/- azathioprine is beneficial.
- Cirrhosis due to autoimmune hepatitis still has 10-year survival of 90%+.
- There is no specific tool to diagnose autoimmune but it can be beneficial
to initiate a trial of corticosteroids.
Hereditary haemochromatosis:
- Usually presents with family history of cirrhosis, skin hyperpigmentation,
diabetes mellitus, pseudogout, and/or cardiomyopathy, all due to signs of
iron overload.
- Laboratory investigation will show fasting transferrin saturation of >
60% and ferritin > 300 ng/mL.
- Genetic testing may be used to identify HFE mutations. If these are
present, biopsy may not need to be performed.
-Treatment is with phlebotomy to lower total body iron levels.
Wilson's disease:
- Autosomal recessive disorder characterized by low serum ceruloplasmin
and increased hepatic copper content on liver biopsy. May also have
Kayser-Fleischer rings in the cornea and altered mental status.
Alpha 1-antitrypsin deficiency (AAT):
- Autosomal recessive disorder. Patients may also have COPD, especially if
they have a history of tobacco smoking. Serum AAT levels are low.
Recombinant AAT is used to prevent lung disease due to AAT deficiency.
Cardiac cirrhosis:
- Due to chronic right sided heart failure which leads to liver congestion.
Galactosemia
Glycogen storage disease type IV
Cystic fibrosis
Drugs or toxins
Certain parasitic infections (such as schistosomiasis)
DIAGNOSIS
The gold standard for diagnosis of cirrhosis is a liver biopsy, through a percutaneous, trans-jugular, laparoscopic, or fine-needle approach.
Histologically cirrhosis can be classified as micronodular, macronodular, or
mixed, but this classification has been abandoned since it is non-specific to the
aetiology, it may change as the disease progresses, and serological markers
are much more specific.
However, a biopsy is not necessary if the clinical, laboratory, and radiologic
data suggests cirrhosis.
Furthermore, there is a small but significant risk to liver biopsy, and cirrhosis
itself predisposes for complications due to liver biopsy.
Endoscopy
(endoscopic examination of the esophagus, stomach and duodenum) is
performed in patients with established cirrhosis to exclude the possibility of
esophageal varices. If these are found, prophylactic local therapy may be
applied (sclerotherapy or banding) and beta blocker treatment may be
commenced.
Rarely diseases of the bile ducts, such as primary sclerosing cholangitis, can
be causes of cirrhosis. Imaging of the bile ducts, such as ERCP or MRCP
(MRI of biliary tract and pancreas) can show abnormalities in these patients,
and may aid in the diagnosis.
More modern scores, used in the allocation of liver transplants but also in
other contexts, are:
- the Model for End-Stage Liver Disease (MELD) score and its pediatric
counterpart,
- the Paediatric End-Stage Liver Disease (PELD) score.
The hepatic venous pressure gradient, i.e. the difference in venous
pressure between afferent and efferent blood to the liver, also determines
severity of cirrhosis, although hard to measure.
A value of 16 mm or more means a greatly increased risk of dying.
Treatment