Blood data

Every single insult of the liver leads to molecular changes in hepatic cells with concomitant changes in corresponding biochemical parameters. A biochemical pattern, which deviates from the norm, allows conclusions to be drawn about the nature and location of the liver damage.¹

There are a range of basic blood tests that should be conducted in the initial diagnosis of HE, these include:²

• Liver function tests
• Blood glucose
• Electrolytes (with calcium and phosphate)
• Creatinine, urea
• Drug screening
• Alcohol level
• Blood gas analysis
• Fasting ammonia concentration
• Cultures (blood, urine, sputum, faeces)
• Hepatitis and HIV
• Ascites (cells and culture)
• Blood picture, c-reactive protein, erythrocyte sedimentation rate²

An overview of liver enzymes which should be investigated¹

Liver cell damage	Cholestasis	Liver function	Mesenchymal activity	Immunology/ Serology
ALT	Alkaline phosphatase	Indirect bilirubin	γ-Globulin	AH-antibody (ab) HBs-antigen (ag)
AST	LAP	Cholinestersase	IgA	HBs-ab HBc-ab
GLDH	γ-GT	Quick`s test	IgG	HBe-ag HBe-ab
γ-GT	GLDH	Albumin	IgM	HBV-DNA HCV-ab
LDH	Direct bilirubin	Bile acid	Copper	HDV ANA
Iron/Ferritin	Bile acid	Fibrinogen	Procollagen-III-peptide	AMA SMA
Zinc	Cholesterol	Ammonia		LMA LKM
	Copper	Indocyanine green		LE
	5´-nucleotidase	Galactose		α1-Fetoprotein

Enzymatic activity Synthesis capability Excretory capability

Liver synthesis function

Albumin is the most important binding and transport protein, synthesised only in the liver. Daily synthesis rate: 15-17 g (12-20% of total protein synthesised in the liver), which can be doubled when necessary. Average daily loss is 1 g via the intestine, 15 mg via the kidneys. Albumin is an important parameter for hepatic albumin synthesis capacity. Low serum albumin levels indicate poor liver function however in chronic liver diseases albumin levels are usually normal until significant liver damage and cirrhosis is present.¹

Quick test (TPT)

Prothrombin is synthesised in the liver, the thromboplastin time (TPT) is a parameter for detecting disturbances in the exogenous blood coagulation system (factors II, V, VII, and X). TPT is determined by measurement of the coagulation time after incubation of citrated plasma with tissue thromboplastin and calcium ions (“Quick test”). Pathological altered prothrombin times indicate an impaired synthesis function of the liver.¹

Liver metabolic function

Ammonia

Ammonia arises from endogenous protein metabolism and it can be formed in all organs of the body. The majority of the ammonia is synthesised by the intestinal flora and is then absorbed into the blood. At physiological pH (~7), about 98% of the ammonia is protonated (NH₄⁺) and 2% is gas (NH₃). Ammonia is 70% eliminated via the urea cycle (periportal) and 30% via glutamine synthesis (perivenous). Plasma ammonia levels are elevated in severe liver disease.¹

Enzymes

The range of enzymes which can be tested to aid in the diagnosis of HE.¹

Enzyme type		Name
Excretion enzymes		AP (alkaline phosphatase) LAP (leucine aminopeptidase) γ-GT (γ-glutamyl transferase) 5´-Nucleotidase
Secretion enzyme		ChE (Cholinesterase)
Indicator enzymes	cytoplasmatic	ALT (alanine aminotransferase) LDH (lactate dehydrogenase )
	mitochondrial	GLDH (glutamate dehydrogenase)
	endoplasmatic	γ-GT, ChE
	mitochondrial/ cytoplasmatic	AST (aspartate aminotransferase)

Liver Function Tests (or Liver Enzymes) – Includes blood tests that assess the general health of the liver. When elevated above normal values, the ALT (alanine aminotransferase) and AST (aspartate aminotransferase) tests indicate liver damage. They are enzymes located in liver cells that can leak out into the bloodstream when liver cells are injured.

Alanine Transaminase (ALT):

• Produced in hepatocytes
• Very specific marker of hepatocellular injury
• Relatively low concentrations in other tissues so more specific than AST
• Levels fluctuate during the day
• Rise may occur with the use of certain drugs or during periods of strenuous exercise.

Aspartate Transaminase (AST):

• Occurs in two isoenzymes, indistinguishable on standard AST assays.
• The mitochondrial isoenzyme is produced in hepatocytes and reacts to membrane stresses in a similar way to ALT.
• The cytosolic isoenzyme is present in skeletal muscle, heart muscle and kidney tissue.
• Caution must be exercised in its use to evaluate hepatocellular damage.
• Usually rises in conjunction with ALT to indicate hepatocellular injury: a hepatitic picture.

Alkaline Phosphatase (ALP):

• A group of isoenzymes that act to dephosphorylate a variety of molecules throughout the body.
• Produced in the membranes of cells lining bile ducts and canaliculi.
• Released in response to the accumulation of bile salts or cholestasis.
• Non-hepatic production in the kidney, intestine, leukocytes, placenta and bone.
• Physiological rise in pregnancy or in growing children.
• Pathological rise in Paget’s disease, renal disease and with bone metastases.

Gamma-glutamyl transferase (GGT):

• Present in liver, kidney, pancreas and intestine.
• It is found in the microsomes of hepatocytes and biliary epithelial cells.
• Elevation of GGT in association with a rise in ALP is highly suggestive of a biliary tract obstruction and is known as a cholestatic picture.
• Subject to rise with hepatic enzyme induction due to chronic alcohol use or drugs such as rifampicin and phenytoin.

Reference: Hall P, Cash J. What is the real function of the liver ‘function’ tests? Ulster Med J. 2012 Jan;81(1):30-6.

Overview of normal liver values:

Serum total Bilirubin	3-17 micromole/litter
Alanine aminotransferase (ALT)	up to 42 u/l
Asparatate amino transferase (AST)	up to 37 u/l
Serum Alkaline Phosphatase (ALP)	60-306 u/l
Total Protein	60-80 g/l
Albumin	40-50 g/l
Gamma Glutamyltransferase GGT	11-60 u/l

	ALP	AST	ALT	GGT	Other Features
Cholestasis Primary Biliary Cirrhosis	↑↑ ↑↑↑	↑ ↑/N	↑ ↑/N	↑↑ ↑↑	AST:ALT<1.5 suggests extrathepatic AST:ALT>1.5 suggests intrahepatic Raised AST:ALT may indicate cirrhosis
Primary Selerosing Cholangitis Alcoholic liver disease	↑↑ ↑/N	↑/N ↑	↑/N ↑	↑↑ ↑↑	AST:ALT>1 may indicate cirrhosis AST:ALT>1.12 indicates risk of oesophageal varices AST:ALT>2
NAFLD/NASH Wilson’s disease	↑/N ↑	↑ ↑↑	↑ ↑↑	↑ ↑	AST:ALT<1 unlesscirrhosis present ALP:bilirubin < 4 AST:ALT>2
Hepatitis B/C Autoimmune hepatitis	↑ ↑	↑↑/N ↑↑	↑↑/N ↑↑	↑ ↑	AST:ALT>1 indicates cirrhosis AST:platelet>1.5 indicates at least moderate fibrosis Enzymes may all be normal Persistently high transaminases indicate poor prognosis
Ischaemic injury/shock liver Toxic injury	↑ ↑	↑↑↑ ↑↑↑	↑↑↑ ↑↑↑	↑ ↑

Reference: Hall P, Cash J. What is the real function of the liver ‘function’ tests? Ulster Med J. 2012 Jan;81(1):30-6.

Further laboratory tests

Immunoglobulin¹

Immunoglobulin measurement is not suitable for general use in liver diagnosis; evaluation may only be useful in combination with other laboratory tests. If ALT levels are persistently high, viral hepatitis serology should be assessed.

Iron/ferritin/copper constellation¹

This may be useful for a detailed liver diagnosis and differential diagnosis of cholestasis and jaundice. Plasma protein fraction (α1-Fetoprotein) is useful as a marker of hepatocellular carcinoma.