Diseases of the liver: Chronic liver disease

By Patrick T F Kennedy and John O'Grady

The commonest causes of chronic or end-stage liver disease are alcohol and chronic viral hepatitis. In addition, there are a number of pathways to chronic liver disease, including auto-immune conditions (eg, auto-immune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis) and metabolic conditions (eg, genetic haemochromatosis and Wilson’s disease).

The severity of chronic liver disease is usually assessed by using the Childs-Pugh classification, which is based on five parameters: ascites, encephalopathy, nutritional status, serum albumin, and serum bilirubin. These parameters carry equal weighting towards the total score, with 15 being the highest attainable score (Table 1). The score is then converted into a designation of either Childs-Pugh A (5–6), B (7–9) or C (10–15) for practical purposes, with C representing the most advanced disease. Patients with Childs-Pugh A are often referred to as having compensated cirrhosis, while the presence of overt clinical complications defines the presence of decompensated disease. Renal function is often impaired in chronic liver disease and may be an important factor to consider in drug management.

The management strategy of any liver disease is a combination of treating the symptoms and complications that arise, as well as drug therapies relevant to the specific underlying diagnosis. Encephalopathy, ascites, spontaneous bacterial peritonitis, variceal bleeding and pruritus are the main complications at which drug therapy is directed. The treatment options for specific liver conditions are increasing, especially in the areas of auto-immune and viral disease. The increasing availability and success of liver transplantation has tended to change the emphasis of management, and it is often not appropriate to exhaust other options before referring the patient for a transplant.

The role of specific drugs in the overall management strategy will vary, depending on physician preference and the relative strength of supporting services in individual institutions. An outline of the approach used at King’s College Hospital (KCH) for a number of complications is given. Below is a discussion of the management of pruritus, ascites, spontaneous bacterial peritonitis, encephalopathy and variceal haemorrhage, as well as the various manifestations of chronic liver disease.

Pruritus

Pruritus (itch) is a prominent symptom of cholestatic liver disease. The pathogenesis of pruritus in cholestatic liver disease remains a matter of debate, but therapies that deplete bile acids, as well as centrally acting agents are effective. Antihistamines are relatively ineffective, apart from their sedative effect, and should not be used as first-line therapy.

Colestyramine and colestipol are anionexchange resins which are the usual first-line therapy. These agents act by binding bile acids and preventing their reabsorption. They are insoluble in water, non-absorbable, and are usually taken before meals to maximise the amount of bile acids sequestered. Colestyramine is usually started at a dose of 4g once or twice daily and colestipol as 5g once or twice daily. The dose is titrated to give adequate relief without causing diarrhoea, but pallatability also restricts dosing. These drugs may reduce the absorption of drugs taken at the same time. To avoid this, drugs should be taken one hour before or four hours after colestyramine or colestipol.¹ Drugs that are particularly susceptible to the absorption-reducing effect of the nionexchange resins are thyroxine, ursodeoxycholic acid (UDCA), digoxin, propranolol, hydrochlorothiazide, tetracycline and penicillins. Long-term therapy with anion-exchange resins can also cause depletion of the fat-soluble vitamins.

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