Cirrhosis of liver is chronic diffuse liver disease of varied etiology and characterized by hepatic cell necrosis, resulting in collapse, proliferation of connective tissue (fibrosis). Nodular regeneration and altered intrahepatic circulation.

Causes

• Viral Hepatic: Hepatitis B, C and D may lead to cirrhosis of liver.
• Alcohol
• Prolonged cholestasis
• Cardiac failure- of long duration induces fibrosis around the central vein.
• Drugs- Isonex, methotrexate and methyl dopa may cause cirrhosis.
• Hemachromatosis- Excessive iron absorption and deposition in the liver leads to cirrhosis. Other features are diabetes, bronze coloured skin and myocarditis. b
• Wilson’s disease- Excessive deposition of copper leads to cirrhosis. Other features are lenticular degeneration (involuntary movements, rigidity), greenish yellow ring at the limbus of cornea (Kayser Fleischer ring) and deficiency of ceruloplasmin.
• Galactosemia- There is deficiency of the enzyme galactose-1-phosphate-uridyl transferase. Galactose from milk diet may have malnutrition, diarrhea, jaundice, cataract and hepatosplenomegaly with cirrhosis of liver.
• Alpha-1-antitrypsin deficiency- The normal levels of this enzyme are 150-350 mg/L. Levels less than 80 mg/L may cause cirrhosis (mechanism unclear), pancreatitis and recurrent lung infections with emphysema.
• Nutrition- A diet low in proteins especially in methionine and choline may cause fatty liver and cirrhosis. A diet rich in unsaturated fats (as in vegetable oils) may increase the susceptibility of liver to cirrhosis. Similarly, a diet very rich in calories and carbohydrates may cause relative protein deficiency and contribute to liver necrosis by infections and toxins.
• Infections- Malaria, kala-azar and dysentery cause malnutrition and contribute to cirrhosis. Schistosomiasis produces hepatic fibrosis which may progress to cirrhosis.
• Toxins-Aflatoxin-contaminated food stuffs may produce cirrhosis. It is produced when groundnuts, pulses or other nuts stored in moist conditions get contaminated with a fungus – Aspergillus flavus. d. Autoimmunity: Autoimmune antibodies as produced in SLE may lead to cirrhosis. e. Cryptogenic: The cause of cirrhosis is not identified. Pathology: The liver is firm, has a gritty feel on cutting and the cut surface shows fibrous bands surrounding nodules of various sizes. Microscopic examination would show necrosis, collapse, fibrosis, regeneration and altered circulation. Regenerating nodules, by compressing the blood supply of the liver cause ischemic damage of the liver even after the disappearance of the primary cause of liver injury.

Clinical Features

Cirrhosis of liver may progress for years before any clinical suspicion is aroused because even 10 percent of healthy liver tissue is adequate for metabolic functions and liver tissue has a remarkable capacity to regenerate. The presenting features of cirrhosis are ascites, edema, hematemesis or hepatic coma. The clinical features can be classified as those due to liver cell failure and those due to portal hypertension.

Due to Liver cell failure:

• Palmar erythema, spider nevi
• Gycaecomastia, testicular atrophy and loss of libido
• Jaundice-usually mild, may be severe terminally
• Ascites, oedema and scrotal swelling
• Flapping tremors
• Alopecia
• Parotid swelling, Dupuytren’s contracture
• Wasting

Due to Portal Hypertension

• Splenomegaly and hypersplenism
• Dilated veins over the chest wall
• Hematemesis, melena and bleeding per rectum
• Ascites

Liver: Liver is usually not palpable because it is shrunken. However in a thin individual or with alcoholic cirrhosis, it may be palpable with a sharp edge and an irregular nodular surface.

Complications

• Due to portal hypertension: Hematemesis, thrombosis of portal vein.
• Due to liver cell dysfunction: Hepatic encephalopathy
• Due to regenerating nodule: Hepatic encephalopathy
• Due to ascites: Hernia
• Due to associated infections: Tuberculosis, pneumonia and secondary bacterial peritonitis.

Labortary investigations

The following findings are typical in cirrhosis:

• Aminotransferases – AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferases do not preclude cirrhosis.
• Alkaline phosphatase – usually slightly elevated.
• GGT – correlates with AP levels. Typically much higher in chronic liver disease from alcohol.
• Bilirubin – may elevate as cirrhosis progresses.
• Albumin – levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver
• Prothrombin time – increases since the liver synthesizes clotting factors.
• Globulins – increased due to shunting of bacterial antigens away from the liver to lymphoid tissue.
• Serum sodium – hyponatremia due to inability to excrete free water resulting from high levels of ADH and aldosterone.
• Thrombocytopenia – due to both congestive splenomegaly as well as decreased thrombopoietin from the liver. However, this rarely results in platelet count < 50,000/mL.
• Leukopenia and neutropenia – due to splenomegaly with splenic margination.
• Coagulation defects – the liver produces most of the coagulation factors and thus coagulopathy correlates with worsening liver disease.

Treatment

• Bed rest till improvement
• Diet: 2000 calories with about 100 gm proteins. Fats and carbohydrates as much as the patient tolerates. Salt is restricted if edema or ascites is present. Supplement Vitamin B complex should be given.
• Spironolactone: This is an aldosterone antagonist which antagonizes the effects of excess aldosterone present in cirrhosis due to inadequate elimination of aldosterone by liver. 100 mg per day may be given.
• Removal of cause: Withdrawal of alcohol, D-penicillamine for Wilson’s disease, etc.
• Corticosteroids and immunosuppressants: This may be helpful in patients with active post-hepatitis cirrhosis.