Mirrors ALP so can be used to confirm if a rise in ALP is of hepatic origin
Raised with alcohol abuse and enzyme-inducing drugs
Bilirubin
Bilirubin
Extravascular haemolysis results in breakdown of Hb → globulin (further broken down into amino acids) + haem (further broken down into bilirubin). This unconjugated bilirubin is then conjugated by the liver so it can be excreted in bile. In advanced liver disease, the liver retains its ability to conjugate bilirubin, but it cannot excrete it.
Albumin makes up more than half of the total protein in the blood. The remainder is made up by globulins (other blood proteins) which include α1-globulins (α1-antitrypsin), α2-globulins (α2-macroglobulin, haptoglobin), β-globulins (complement, transferrin), and γ-globulins (immunoglobulins). Albumin is synthesised by the liver and has a half-life of around 20 days. Hence, changes in levels happen over weeks.
↓albumin + ↓total protein = cirrhosis, nephrotic syndrome, chronic inflammation, protein-losing enteropathy, alcoholism, protein malnutrition/malabsorption
↓albumin + normal total protein = infection (albumin is a negative acute phase protein)
↓albumin + ↑ total protein = myeloma, Waldenström’s
Prothrombin time/INR
PT/INR depend on clotting factors and fibrinogen which are synthesised by the liver. Some clotting factors have short half-lives (e.g. 6-8 hours) so changes can occur rapidly.
Thrombocytopenia = effect of alcohol on bone marrow, hypersplenism, liver cirrhosis or disseminated intravascular coagulation
Further investigations to find cause
Blood tests
Viral
Viral hepatitides: hepatitis A IgM, hepatitis B surface antigen, hepatitis C IgG, hepatitis E IgM
CMV serology
EBV serology
Autoimmune liver screen
Anti-smooth muscle (autoimmune hepatitis type 1)
Anti-mitochondrial (primary biliary cholangitis)
Anti-liver-kidney microsomal (autoimmune hepatitis type 2, hepatitis C/D, drug-induced hepatitis)
Antinuclear (autoimmune hepatitis type 1, SLE)
Tumour markers – if cirrhosis/weight loss
α- fetoprotein (hepatocellular carcinoma)
Infiltrative
Ferritin and transferrin saturation (haemochromatosis) – but be aware ferritin is also an acute phase protein
Serum copper and caeruloplasmin ± 24-hour urinary copper (Wilson’s disease)
Fasting glucose and lipids (fatty liver disease)
Metabolic
α1-antitrypsin (α1-antitrypsin deficiency)
Immunoglobulins and protein electrophoresis (IgM raised in primary biliary cholangitis, IgA raised in alcoholic liver disease, IgG raised in autoimmune hepatitis)
Abdominal ultrasound: first line imaging (quick and cheap) that is useful for determining liver texture, size and presence of any gallstones or cholecystitis
Abdominal CT: can confirm pancreatitis or tumour
Elastography: grades liver fibrosis in chronic liver disease non-invasively
Magnetic resonance cholangiopancreatography: to look for duct disease/stones if ultrasound normal
Procedures
Ascitic tap: if ascites present
Liver biopsy (CT-guided usually, but done trans-jugular if there is ascites or coagulopathy)
A 17 year old student presents with a fever and sore throat. He has cervical lymphadenopathy. His full blood count shows a lymphocytosis. Liver function tests reveal: ALT 1020, ALP 130, Bilirubin 27, Albumin 36.
A 20 year old female with severe depression and bipolar disorder presented to the acute medical unit after a paracetamol overdose. Her paracetamol level is checked and is over the treatment line. Her ALT is 62 but her other liver function tests are normal.
A 54 year old who drinks 1L vodka daily, presents with vomiting. On examination, he seems to be tremulous and is confused. He has large volume ascites. His blood tests are taken and his liver function tests are as follows: ALT 122, ALP 22, Bilirubin 120, Albumin 22. His coagulation test reveals: INR 3.0. His renal function test reveals: Na+ 128, K+ 4, Ur 6, Cr 190.
An ascitic fluid aspirate is taken and the ascitic white cell count is raised. What are you concerned about and what additional treatments would you administer?