What blood tests are used to assess hepatic (liver) function and investigate hepatic pathologies?

Blood Tests for Hepatic Function and Pathology Assessment

Initial Standard Liver Panel

The initial investigation for potential liver disease should include bilirubin, albumin, ALT, ALP, and GGT, together with a full blood count if not already performed within the previous 12 months. 1, 2

Core Components and Their Functions

• Bilirubin measures the liver's ability to process waste products and conjugate bilirubin for excretion 2
• Albumin indicates the synthetic function of the liver and reflects hepatic protein production capacity 1, 2
• ALT (Alanine Aminotransferase) is the primary marker for hepatocellular injury and necro-inflammatory liver disease 1, 2
• ALP (Alkaline Phosphatase) is associated with biliary disease and cholestatic patterns 2
• GGT (Gamma-Glutamyl Transferase) increases sensitivity for detecting alcohol-related and non-alcoholic fatty liver disease, though it reduces specificity 1, 2
• Full Blood Count is essential to assess platelet count, as thrombocytopenia may indicate advanced liver disease with portal hypertension 1, 2

Important Note on AST

• AST is not recommended in the initial panel but should be added when calculating fibrosis risk scores 2
• The AST:ALT ratio >1 suggests advanced fibrosis or cirrhosis 2
• AST combined with ALT and platelet count enables calculation of FIB-4 score for fibrosis assessment 1

Additional Tests for Comprehensive Assessment

Synthetic Function Tests

• PT/INR (Prothrombin Time/International Normalized Ratio) should be measured when evaluating synthetic liver function and is incorporated into Child-Pugh and MELD scoring systems 1
• Creatinine is an established prognostic marker in patients with liver disease and is essential for MELD score calculation 1

Standard Liver Aetiology Screen (Second-Line Testing)

When liver blood tests are abnormal, a standard liver aetiology screen should be performed to identify the underlying cause. 1, 2

Core Aetiology Panel

• Hepatitis B surface antigen (HBsAg) to detect chronic hepatitis B infection 1
• Hepatitis C antibody with follow-on PCR if positive to confirm active infection 1
• Ferritin and transferrin saturation to screen for iron overload; transferrin saturation >45% suggests haemochromatosis 1
• Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody to detect autoimmune liver disease 1
• Serum immunoglobulins as raised IgG suggests autoimmune hepatitis 1

Extended Aetiology Panel (When Core Panel is Negative)

• Anti-LKM (liver kidney microsome) antibody for type 2 autoimmune hepatitis 1
• Coeliac antibodies as coeliac disease can cause abnormal liver tests 1
• Alpha-1-antitrypsin level to screen for alpha-1-antitrypsin deficiency 1
• Thyroid function tests as thyroid disorders can affect liver enzymes 1
• Caeruloplasmin for patients aged 3-40 years to screen for Wilson's disease 1

Pattern Recognition and Interpretation

Hepatocellular Pattern

• Predominantly elevated ALT and AST indicate hepatocellular injury 1
• For marked elevations in ALT (>1000 U/L), consider acute viral hepatitis including hepatitis A, E, and cytomegalovirus 1

Cholestatic Pattern

• Predominantly elevated ALP and GGT indicate biliary obstruction or cholestatic disease 1
• Consider primary sclerosing cholangitis (PSC) in patients with cholestatic enzymes and inflammatory bowel disease history 1
• Dilated bile ducts on imaging require urgent assessment and possible hospital referral 1

Advanced Disease Indicators

• AST:ALT ratio >1 suggests advanced fibrosis or cirrhosis 2
• Thrombocytopenia results from splenic sequestration in portal hypertension, decreased thrombopoietin production, and increased platelet destruction 1
• Low albumin and elevated bilirubin indicate impaired synthetic function 1

Critical Pitfalls to Avoid

• Do not simply repeat the same panel of tests when abnormal results are found; 84% of abnormal liver tests remain abnormal at 1 month, and 75% at 2 years 1
• Normal liver tests do not exclude significant liver disease, particularly in apoptotic diseases like fatty liver disease where enzymes may be normal despite advanced fibrosis 1, 2
• Isolated elevated ferritin is commonly seen in dysmetabolic iron overload syndrome (NAFLD, alcohol excess) and does not reflect haemochromatosis unless transferrin saturation is also elevated 1
• GGT elevation alone has low specificity but is associated with increased liver and all-cause mortality 1
• Children require different thresholds for referral as common adult causes are less prevalent and the differential diagnosis is wider 1

High-Risk Population Screening

For high-risk patients (injecting drug users, migrants from high-prevalence areas, prisoners), consider simultaneous second-line testing rather than sequential testing. 1, 2

• Confirm viral load in patients positive for HBsAg, HBcAb IgG, or HCV antibodies 1
• Isolated HBcAb IgG may still indicate chronic HBV infection and requires viral load confirmation 1

Fibrosis Assessment in Low-Prevalence Populations

• FIB-4 score (calculated from age, AST, ALT, and platelet count) should be used as a first-tier test to rule out advanced fibrosis in at-risk populations 1
• For patients over 65 years, lower cut-offs (<2.0) should be used for FIB-4 interpretation 1
• Non-invasive tests have lower sensitivity and higher specificity in low-prevalence populations due to spectrum effect 1