Signs and tests of acute and chronic liver disease

Liver function and tests

    Adequate liver function is essential to survival; humans will survive for only 24—48 hours in the an hepatic state despite full supportive therapy. The main functions of the liver are shown in Table 52.1. Routinely available tests of liver func­tion are shown in Table 52.2. Bilirubin is synthesised in the liver and excreted in the bile. Increased levels may be associated with increased haemoglobin breakdown, hepato­cellular dysfunction resulting in impaired bilirubin transport and excretion or from biliary obstruction. In patients with known parenchymal liver disease progressive elevation of bilirubin level in the absence of a secondary complication suggests deterioration in liver function. The serum alkaline phosphatase is particularly elevated with cholestatic liver dis­ease or biliary obstruction. The transaminase levels [aspartate transaminase (AST) and alanine transaminase (ALT)] reflect acute hepatocellular damage, as does the gamma-glutamyl transpeptidase (GGT) level which may be used to detect the liver injury associated with acute alcohol ingestion. The syn­thetic functions of the liver are reflected in the ability to synthesise proteins (albumin level) and clotting factors (pro­thrombin time). The standard method of monitoring liver function in patients with chronic liver disease is serial measurements of bilirubin, albumin and prothrombin time.

Signs of impaired liver function

The clinical signs associated with impaired liver function depend on the severity of dysfunction and whether it is acute or chronic.

Acute liver failure

The main causes of acute liver failure are shown in Table 52.3. In the early stages there may be no objective signs, but with severe dysfunction the onset of clinical jaundice may be associated with neurological signs of liver failure consisting of a liver flap, drowsiness, confusion and, eventually, coma. Treatment in the majority of cases is supportive therapy to allow the liver to recover from the acute damage. This may include intravenous fluids and nutrition, renal support with haemofiltration, antibiotics for secondary infective episodes, sedation and ventilation for the development of hepatic coma, and mannitol for cerebral oedema. The overall mortal­ity for acute liver failure is approximately 50 per cent, even with the best the supportive therapy. Liver transplantation is appropriate for some patients with acute liver failure, although the overall results are poor in comparison to liver transplantation for chronic liver disease. Indications for orthotopic (OLT) liver transplantation, based on the King’s College London transplant experience, are given in Table 52.4.

Chronic liver disease

Because of the many diverse functions of the liver, patients with chronic liver disease may present in many different ways. Lethargy and weakness are common features irrespec­tive of the underlying cause. Often this precedes clinical jaundice which indicates the liver’s inability to metabolise bilirubin. The serum level reflects the severity of the underlying liver disease. Progressive deterioration in liver function is associated with a hyperdynamic circulation involving a high cardiac output, large pulse volume, low blood pressure and flushed warm extremities. Fever is a common feature which may be related to underlying inflammation and cyto­kine release from the diseased liver or due to bacterial infection to which patients with chronic liver disease are predisposed. Skin changes may be evident, including spider naevi, cutaneous vascular abnormalities which blanch on pressure, palmar erythema and white nails (leuconychia). Endocrine abnormalities are responsible for hypogonadism and gynaecomastia. The mental derangement associated with chronic liver disease is termed ‘hepatic encephalopathy’. This is associated with memory impairment, confusion, persona­lity changes, altered sleep patterns and slow slurred speech. The most useful clinical sign is the flapping tremor demonstrated by asking the patient to extend his arms and hyperextend the wrist joint. Abdominal distension due to ascites is a common late feature. This may be suggested clinically by the demonstration of a fluid thrill or shifting dullness. Protein catabolism produces loss of muscle bulk and wasting, and a coagulation defect is suggested by the presence of skin bruising. A patient with the typical features of end-stage chronic liver disease is shown in (Fig. 52.3.) The Child’s classification allows an easy method of describing the severity of liver disease and allows comparison of treatments for patients with chronic liver disease (Table 52.5).