Abnormal liver enzymes: A review for clinicians

Table 1 Liver biochemical tests and their respective sites and functions

Interpretation	Test	Site (s)	Function
Hepatocellular integrity	ALT	Hepatocyte (main), cardiac, renal and muscle tissue to smaller extent	Amino acid catabolism. Glutamate and pyruvate production for ATP production
	AST	Hepatocyte, cardiac, muscle and brain tissue
	LDH	Nonspecific, present widely in the body	Anaerobic glycolysis major enzyme in addition to NADH production. Significant in ischemic hepatitis
Cholestatic pattern	ALP	Hepatobiliary tract, bone, placenta and intestines	Dephosphorylation reactions. Role in bile production
	GGT	Mainly in hepatobiliary tract, present in multiple other organs (nonspecific as an isolate test)	Aids in identification of elevated ALP of biliary origin
	5’nucleotidase	Nonspecific, present widely in the body	Clinical value in hepatobiliary and cholestatic disease specifically when paired with ALP and GGT
	Bilirubin	Serum and liver	End product of heme breakdown. Exists in conjugated and unconjugated form. Elevation in conjugated suggestive of possible cholestasis
Synthetic function	Albumin	Serum	Main protein in the serum, maintains oncotic pressure. Produced by the liver
	PT/INR	Test to measure extrinsic coagulation pathway	Clotting factors primarily produced in the liver. Helpful however does not reflect true coagulation status

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LDH: Lactate dehydrogenase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; ATP: Adenosine-triphosphate; PT: Prothrombin time; INR: International normalized ratio.

Table 2 R-value calculation and interpretation

R value = (ALT ULN ALT)/(ALP ÷ ULN ALP)
R value	Interpretation
> 5	Hepatocellular pattern
> 2 but < 5	Mixed pattern
< 2	Cholestatic pattern

ALT: Alanine aminotransferase; ULN: Upper limit of normal; ALP: Alkaline phosphatase.

Table 3 Common condition with abnormal liver biochemical tests

Condition	AST/ALT	ALP	GGT	Bilirubin	Other
Alcoholic hepatitis	↑↑ AST:ALT > 2	↑	↑	↑	AST/ALT < 500
NAFLD	-/↑ ALT > AST	-/Mild ↑	-/Mild ↑	↑ If progress to cirrhosis	-
Viral hepatitis	↑↑ In acute/↑ in chronic	↑	↑	↑ In chronic	AST:ALT > 1 suggestive of cirrhosis
Hemochromatosis	↑ ALT > AST	↑	↑	↑ Higher levels = higher iron load	↑ Ferritin and transferrin saturation
Wilson’s disease	↑/↑↑↑ AST:ALT > 2.2 in ALF	↑	↑	↑	ALP:Bilirubin < 4
AATD	↑ AST > ALT	-	-	-	-
Celiac disease	↑ ALT > AST	-	-	-	-
Autoimmune hepatitis	↑↑	↑	↑	↑	ALP:AST/ALT < 3
DILI	↑↑/↑↑	↑	↑	↑	↑ PT/INR
Cholestasis	↑	↑↑	↑↑	↑	AST:ALT < 1.5 – ExtrahepaticAST:ALT > 1.5 - Intrahepatic

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; NAFLD: Non-alcohol fatty liver disease; AATD: Alpha-1 antitrypsin deficiency; DILI: Drug induced liver injury; PT: Prothrombin time; INR: International normalized ratio.

Table 4 Non-alcoholic fatty liver disease spectrum

Non-alcoholic fatty liver disease spectrum
NAFL	Steatosis changes. No cellular ballooning, hepatocyte inflammation or fibrosis	Prevalence of 25% approximately. Reversible
NASH	Steatosis changes. Cellular ballooning and hepatocyte inflammation. No fibrosis	Prevalence of 1.5%-6.45% approximately. Generally irreversible (has been found to be reversible in some patients)
NASH related liver cirrhosis	Hepatocyte destruction and fibrosis	Prevalence of 1%-2% approximately. Irreversible
Healthy liver ←→ NAFL → NASH → NASH related cirrhosis

NAFL: Non-alcoholic fatty liver; NASH: Non-alcoholic steatohepatitis.