🔬 Liver Function Tests

Liver Function Tests (LFTs) are a group of biochemical markers used to screen for and monitor liver disease or biliary tract involvement. The panel typically includes bilirubin, liver enzymes (ALT, AST, ALP, GGT), and albumin. While they indicate hepatocyte damage or cholestasis, markers like albumin and Prothrombin Time (PT) are required to assess actual synthetic function. LFTs are essential for evaluating jaundice and monitoring hepatotoxic medications.

Indications include jaundice, abdominal pain (especially RUQ), nausea/vomiting, or hepatomegaly. It is also used to screen for liver damage in patients with risk factors like heavy alcohol use, obesity, or high-risk drug use. Routine monitoring for patients on potentially hepatotoxic drugs is standard. It is also used in the investigation of metabolic bone diseases (due to ALP) and as part of a 'metastatic screen' in oncology since many cancers spread to the liver.

A venous blood sample is collected into a serum separator tube (SST, yellow top). The laboratory uses automated photometric assays to measure enzyme activities and protein concentrations. Results are typically available within hours. In some cases, a 'liver screen' is triggered by abnormal LFTs, which includes viral serology, autoantibodies (e.g., AMA, ANA, ASMA), iron studies, and alpha-1 antitrypsin levels.

A normal LFT panel includes Bilirubin (<21 micromol/L), Alanine Aminotransferase (ALT, <40 IU/L), Aspartate Aminotransferase (AST, <40 IU/L), Alkaline Phosphatase (ALP, 30-130 IU/L), Gamma-glutamyltransferase (GGT, <60 IU/L), and Albumin (35-50 g/L). Note that reference ranges vary slightly by lab. Normal findings suggest no acute hepatocyte injury or significant cholestasis. Normal albumin and PT suggest preserved synthetic function.

Interpretation should focus on the 'pattern' of elevation. An ALT >1000 IU/L is usually seen in ischaemic hepatitis, severe viral hepatitis, or drug-induced injury. If ALP is raised, checking GGT helps confirm if the origin is hepatic (GGT also high) or bony (GGT normal). Bilirubin levels reflect a balance between production, conjugation, and excretion; conjugated bilirubin in the urine (dark urine) always indicates pathology. Note that 'LFTs' do not truly measure liver 'function' (except albumin and PT); they mostly measure liver 'damage'.

A 'hepatocellular' pattern is defined by a primary rise in ALT/AST, suggesting direct liver cell damage (e.g., viral hepatitis, paracetamol overdose, NAFLD). A 'cholestatic' pattern features a dominant rise in ALP and GGT, suggesting bile duct obstruction or intrahepatic cholestasis (e.g., gallstones, PBC, pancreatic cancer). Isolated hyperbilirubinaemia (predominantly unconjugated) often suggests Gilbert’s syndrome or haemolysis. Low albumin and prolonged PT/INR are markers of impaired synthetic function, often seen in cirrhosis or end-stage liver disease. High GGT is often associated with alcohol excess but is non-specific.

LFTs are used to screen for liver disease, monitor the toxicity of medications (e.g., statins, methotrexate), and investigate jaundice. They help differentiate between surgical jaundice (obstruction) and medical jaundice (hepatitis). In the context of pregnancy, abnormal LFTs may indicate obstetric cholestasis or HELLP syndrome. Synthetic markers (Albumin and PT) are more clinically significant for prognosticating chronic liver disease than the enzymes themselves. Many patients with chronically abnormal LFTs in the UK require investigation for NAFLD or alcohol-related liver disease.

Interpreting ALP in isolation without considering bone disease or pregnancy is a common error. Overlooking a low albumin level, which might be due to nephrotic syndrome or malnutrition rather than liver disease. Relying on LFTs alone to 'rule out' liver disease in a patient with risk factors for cirrhosis. Failing to account for the effect of muscle injury (rhabdomyolysis) on AST levels. Statin-induced enzyme rises are often mild; stopping the drug unnecessarily for minor elevations is common.

LFTs can be entirely normal in patients with compensated cirrhosis or well-controlled chronic hepatitis. They are non-specific; ALP is found in bone, placenta, and intestine, meaning an elevation does not always imply liver disease. AST is found in cardiac and skeletal muscle, so it may rise in MI or rhabdomyolysis. The tests do not provide a definitive diagnosis or indicate the degree of fibrosis; further imaging or specialized tests (e.g., FibroScan) are usually required.

Differentiate between ALT (more specific to the liver) and AST (found in muscle/heart). Use the AST:ALT ratio to help identify alcohol-related injury (typically >2:1). Remember that a raised ALP in a teenager is often physiological due to bone growth. In the MLA, focus on the management of deranged LFTs in the context of sepsis, paracetamol overdose, and common hepatobiliary conditions.