Cirrhosis consists of fibrosis of the hepatic parenchyma resulting in nodule formation. It represents the consequences of a sustained wound-healing response to chronic liver injury from a variety of causes, including toxins eg. alcohol, chronic viral infection, cholestasis, and metabolic disorders. The clinical manifestations of cirrhosis vary widely, from lack of symptoms to liver failure, and are determined by both the nature and severity of the underlying liver disease as well as the extent of fibrosis. It is the most common non-neoplastic cause of death, among hepatoboliary and digestive diseases. It was the 12 th leading cause of death in the United States in 2000, accounting for more than 25,000 deaths.

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Cirrhosis has many causes. Chronic alcoholism, hepatitis B and C are the most common ones.

Alcoholic cirrhosis usually develops after more than a decade of heavy drinking. The amount of alcohol that can injure the liver varies greatly from person to person.

Infection with hepatitis virus causes inflammation and low grade damage to the liver that over several decades can lead to cirrhosis.

The causes for hepatic cirrhosis are listed below:

 I.  Presinusoidal fibrosis
     A.  Schistosomiasis
     B.  Idiopathic portal fibrosis

II.  Parenchymal (sinusoidal) fibrosis (true cirrhosis)
     A.  Drugs and toxins

1.  Alcohol
2.  Methotrexate
3. Isoniazid
4.  Vitamin A
5.  Amiodarone
6.  Perhexiline maleate
7.  a -Methyldopa
8. Oxyphenisatin

     B. Infections

1. Chronic hepatitis B or C
2. Brucellosis
3. Echinococcosis
4. Congenital or tertiary syphilis

     C.  Autoimmune

1. Autoimmune chronic hepatitis – types 1, 2 and 3

     D. Vascular abnormalities

1. Chronic, passive congestion due to right sided heart failure, pericarditis
2. Hereditary hemorrhagic telangiectasias (Osler-Weber-Rendu)

     E.  Metabolic/genetic diseases

1. Wilson's disease
2. Hemochromatosis
3. a 1 -Antitrypsin deficiency
4. Carbohydrate disorders (eg. Fructose intolerance, galactosemia, glycogen storage diseases)
5. Lipid disorders (eg. Wolman's disease, abetalipoproteinemia)
6. Urea cycle defects (eg. Ornithine transcarbarmylase)
7. Porphyria
8. Amino acid disorders (eg. Tyrosinosis)
9. Bile acid disorders (eg. Byler's disease)

      F.  Biliary obstruction

1. Primary biliary cirrhosis
2. Secondary (“mechanical”) biliary obstruction

              a. Primary sclerosing cholangitis
              b. Neoplasm of bile ducts or pancreas
              c. Iatrogenic or inflammatory biliary structure

         3. Cystic fibrosis
         4. Biliary atresia/neonatal hepatitis
         5.Congenital biliary cysts

     G. Idiopathic/ miscellaneous

III. Post-sinusoidal fibrosis

      A. Veno-occlusive disease

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Cirrhosis has traditionally been classified as either macrondoular (> 3 mm nodules) or micronodular (< 3 mm) or mixed. Regeneration in a micronodular cirrhosis results in a macrondoular or mixed appearance. With time micronodular cirrhosis often converts to macrondoular. There is no etiologic, functional, or prognostic value to the nodule size.

Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience symptoms.

Clinical manifestations can be broadly classified into those resulting from impaired hepatocellular function, such as jaundice and coagulopathy, and those that result from physical disruption of the parenchyma, such as gastroesophageal varices and ascites.

Compensated cirrhosis
The disease may be discovered at a routine examination or biochemical screen, or at operation undertaken for some other condition. Cirrhosis may be suspected if the patient has mild pyrexia, vascular spiders, palmar erythema, or unexplained epistaxis or oedema of the ankles. Firm enlargement of the liver and splenomegaly are helpful diagnostic signs. Vague morning indigestion and flatulent dyspepsia may be early features in the alcoholic cirrhotic.

Decompensated cirrhosis
The patient usually seeks medical advice because of ascites and/or jaundice. General health fails with weakness, muscle wasting and weight loss. Continuous mild fever is often due to gram-negative bacteremia, to continuing hepatic cell necrosis or to a complicating liver cell carcinoma. Fetor hepaticus may be present. Cirrhosis is the commonest cause of hepatic encephalopathy.

Jaundice implies that liver cell destruction exceeds the capacity for regeneration and is always serious. The deeper the jaundice the greater the inadequacy of liver cell function.

 The skin may be pigmented. Clubbing of the fingers is occasionally seen. Purpura over the arms, shoulders and shins may be associated with a low platelet count. Spontaneous bruising and epistaxis reflect a prothrombin deficiency. The circulation is over-active. The blood pressure is low. Sparse body hair, vascular spiders, palmar erythema, white nails and gonadal atrophy are common.

Ascites is usually preceded by abdominal distension. Oedema of the legs is frequently associated.

The liver may be enlarged, with a firm regular edge, or contracted and impalpable. The spleen may be palpable.

The diagnosis of cirrhosis depends on demonstrating widespread nodules in the liver combined with fibrosis. This may be done by :

Direct Visualization : Laparoscopy visualizes the nodular liver and allows directed liver biopsy. However, laparotomy should never be used to diagnose cirrhosis because it may precipitate liver failure even in those with very well-compensated disease.

Radioisotope scanning: This may show decreased uptake, an irregular pattern and uptake by spleen and bone marrow. Nodules are not identified.

Ultrasonography: Using ultrasound, cirrhosis is suggested by dense reflective areas of irregular distribution and increased echogenicity. The caudate lobe is enlarged relative to the right lobe. However, ultrasound is not reliable for the diagnosis of cirrhosis unless ascites is present. Regenerating nodules may be shown as focal lesions. These should be considered malignant unless proved otherwise by serial imaging and a -fetoprotein levels.

CT scan: Liver size can be assessed and the irregular nodular surface seen. CT scan does not visualize benign regenerative nodules.

Liver biopsy: Biopsy confirms the diagnosis. It may give a clue to etiology and activity.

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Loss of liver function affects the body in many ways. Following are the common problems, or complications, caused by cirrhosis.

Oedema and ascites: When the liver loses its ability to make the protein albumin, water accumulates in the legs and abdomen.

Bruising and bleeding: When the liver slows or stops production of the proteins needed for blood clotting, a person will bruise or bleed easily. The palms of the hands may be reddish and blotchy with palmar erythema.

Jaundice: Jaundice is a yellowing of the skin and eyes that occurs when the diseased liver does not absorb enough bilirubin.

Gallstones: If cirrhosis prevents bile from reaching the gallbladder, gallstones may develop.

Neurological: A damaged liver cannot remove toxins from the blood, causing them to accumulate in the blood and eventually the brain. There, toxins can dull mental functioning and cause personality changes, coma, and even death.

Sensitivity to medication: Cirrhosis slows the liver's ability to filter medications from the blood. Because the liver does not remove drugs from the blood at the usual rate, they act longer than expected and build up in the body. This causes a person to be more sensitive to medications and their side effects.

Portal hypertension: Normally, blood from the intestines and spleen is carried to the liver through the portal vein. But cirrhosis slows the normal flow of blood through the portal vein, which increases the pressure inside it. This leads to portal hypertension.

Varices: When blood flow through the portal vein slows, blood from the intestines and spleen backs up into blood vessels in the stomach and esophagus. If these burst, the result is a serious bleeding problem in the upper stomach or esophagus that requires immediate medical attention.

Insulin resistance and type 2 diabetes: Cirrhosis causes resistance to insulin, which may eventually lead to development of diabetes.

Liver cancer: Primary liver cancer is frequent sequelae of cirrhosis.

Others: Cirrhosis can cause immune system dysfunction, leading to infection. It can also lead to impotence, kidney dysfunction and failure, and osteoporosis.

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Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Removing the primary insult when possible remains the most effective way to prevent irreversible scaring. Treatment depends on the cause of cirrhosis and any complications a person is experiencing.

The management of the well-compensated cirrhotic is directed towards the early detection of hepato-cellular failure. An adequate balanced diet and avoidance of alcohol are essential.

A diet of 1 g of protein per kilogram of body weight is adequate unless the patient is obviously malnourished.

The treatment of cirrhosis may lie in switching off collagen synthesis. Trials are underway with drugs such as colchicine but these have not yet been approved for use. Other therapeutic agents for the future include the augmentation of the activity of extra-cellular proteases responsible for degrading collagen.

When complications cannot be controlled or when the liver becomes so damaged from scarring that it completely stops functioning, a liver transplant is necessary.

Management of cirrhotic ascites: Ascites is the most frequent complication of liver cirrhosis and is associated with a marked worsening of prognosis.

Treatment of ascites in cirrhosis is based on bed rest, low sodium diet and diuretics. However, a restricted sodium and fluid diet may not be sufficient to prevent excessive fluid accumulation in approximately only 10-20% of cirrhotic patients . Loop diuretics, like frusemide and torsemide and aldosterone antagonists, such as spironolactone, are the most commonly used diuretics in patients with cirrhosis and ascites.

Encepahlopathy: Complicating encepahlopathy is an indication for lowered protein intake and lactulose or lactitol.

Portal hypertension: Antihypertensive drugs like beta-blocker are used to lower the raised pressure.

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The prognosis is determined by the extent of hepatocellular failure. Jaundice, spontaneous bruising and ascites resistant to treatment are grave signs. If specific treatment is available the outlook is better.

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