CHAPTER 30 EVALUATING ABNORMAL LIVER TESTS

KEY POINTS

• Liver enzyme abnormalities may be physiological or pathological.

• Any persistent elevation of liver function tests must be investigated.

• A detailed history and physical examination is mandatory.

• The degree and pattern of elevation of liver tests may provide clues to its aetiology.

• Upper abdominal ultrasonography is a useful non-invasive imaging procedure.

INTRODUCTION

Liver function tests (LFTs) are commonly performed as part of routine screening laboratory investigations. These include estimations of serum:

• alanine aminotransferase (ALT)

• aspartate aminotransferase (AST)

• alkaline phosphatase (ALP)

• gamma-glutamyltransferase (GGT)

• bilirubin (hepatic excretory function)

• albumin (hepatic synthetic function).

An elevated prothrombin time that is not corrected by the administration of vitamin K suggests reduced hepatic synthetic function.

Thrombocytopenia in the context of liver disease suggests hepatic fibrosis and impaired liver function with concomitant portal hypertension.

APPROACH TO THE PATIENT WITH ABNORMAL LFTs

The presence of any persistent abnormality of liver tests warrants further assessment. The initial step in evaluating a patient with raised liver enzymes is to undertake a thorough history and physical examination, with particular emphasis on risk factors for liver disease.

A detailed drug history is important including:

• prescribed medications in particular, antibiotics during the preceding 3 months

• alcohol intake

• ingestion of allopathic and traditional medications including vitamins and herbal preparations (CAM: complementary and alternatives medicines)

• recreational drugs.

Liver injury may manifest several weeks after drug cessation.

Risk factors for viral hepatitis must be elicited such as injecting drug use.

Sudden, marked elevations in transaminase levels necessitates exclusion of viral, drug-induced and ischaemic hepatitis.

INTERPRETING PATTERNS OF LIVER TEST ABNORMALITIES

The degree and pattern of liver tests’ elevation may provide clues as to aetiology (Figure 30.1). A practically useful classification is provided below.

FIGURE 30.1 Evaluating liver function test abnormalities.

Liver test abnormalities are designated as:

1. ‘Hepatocellular’ when there is an ALT increase of over twice the upper limit of normal or R ≥5, where R is the ratio of serum ALT/serum ALP in multiples of the upper limit of the normal range

2. ‘Cholestatic’ if serum ALP is increased above twice the upper limit of the normal range or R ≤2

3. ‘Mixed’ in pattern when both ALT and ALP are raised, and 2 ≤R ≤5. The ratio R may vary during the course of liver injury.

In the vast majority of patients with liver disease, the serum ALT exceeds the AST. Exceptions include those with alcoholic liver disease and those with cirrhosis from any aetiology.

The presence of liver test abnormalities in association with a low serum albumin or a prolonged prothrombin time infers significantly impaired hepatic synthetic function, while an elevated bilirubin reflects hepatic excretory dysfunction.

Disorders associated principally with elevations in aminotransferase levels

Aminotransferase levels are sensitive indicators of hepatic injury; ALT and AST are present normally in serum at low levels, usually less than 30–40 U/L.

AST is found in:

• liver

• cardiac muscle

• skeletal muscle

• kidneys

• brain

• pancreas

• lungs

• leucocytes and erythrocytes.

Because the highest levels of ALT are in the liver, an elevation of ALT is a more specific indicator of liver injury than the AST.

Common causes of liver enzyme abnormalities according to the pattern of enzyme elevation are presented in Table 30.1.

TABLE 30.1 Causes of elevated liver enzyme levels

Hepatocellular	Cholestatic
• Excessive alcohol consumption	• Drug-induced liver injury
• Drug-induced liver disease	• Choledocholithiasis
– Chronic hepatitis B and C	• Primary biliary cirrhosis
– Non-alcoholic fatty liver disease	• Primary sclerosing cholangitis
– Haemochromatosis	• Pancreatic carcinoma
• Autoimmune hepatitis	• Neoplastic infiltration
• Wilson’s disease	• Sarcoidosis
• Alpha1-antitrypsin deficiency

Additional laboratory tests useful in identifying specific disorders are listed in Table 30.2.

TABLE 30.2 Laboratory tests to clarify the cause of liver test abnormalities

Laboratory test	Diagnosis
• Hepatitis C antibody	• Positive test suggests chronic hepatitis C infection
• Hepatitis B surface antigen	• Positive test suggests chronic hepatitis B infection
• Hepatitis B e antigen	• Positive test suggests active viral replication
• Serum ferritin, transferrin saturation	• Iron overload suggests haemochromatosis
• Antimitochondrial antibodies	• Detected in primary biliary cirrhosis
• Antinuclear antibodies, anti-smooth muscle antibodies	• Detected in autoimmune hepatitis
• Serum caeruloplasmin	• Reduced in Wilson’s disease
• Serum alpha1-antitrypsin	• Decreased in alpha1-antitrypsin deficiency

Causes of elevated aminotransferase levels

Alcohol-related liver disease (ALD)

• The diagnosis of alcohol-related liver disease is supported by the finding of a ratio of AST to ALT of at least 2:1.

• The degree of elevation of aminotransferase levels may provide further evidence for a diagnosis of ALD. It is rare for AST levels to be greater than 8 times the normal value in patients with alcohol abuse, and even less common for ALT levels to exceed 5 times the normal value. ALT levels may be normal in patients with severe ALD.

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