Before you read liver function tests (LFTs), recall the function of the liver. The liver is located in the right upper abdomen of the body, covered by ribs, and the upper edge is close to the level of the nipple. Its main job is to break down or expel various drugs, poisons and some metabolites through biotransformation, synthesize proteins and coagulation factors, produce bile needed for digestion, and also play an important role in metabolism, glucose synthesis and storage.
Liver function test items mainly include: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamine transferase (GGT), serum bilirubin, prothrombin time (PT), international normalized ratio (INR) and albumin. These tests can help assess exactly what is wrong with the body and can support histological differential diagnosis based on the degree to which these indicators are elevated.
The term "liver function test" is used incorrectly because many tests do not assess liver function, but rather indicate where the source of the damage lies. ALT/AST levels are much higher than ALP/bilirubin, suggesting hepatocyte necrosis. Conversely, if ALP/bilirubin is elevated much greater than ALT/AST, cholestasis is indicated.
Differential diagnosis based on elevated LFTs
Hepatocyte type
Aminotransferase is elevated and much higher than alkaline phosphatase.
Elevated ALT: acute or chronic viral hepatitis, NAFLD, acute Budd-Gerard syndrome, ischemic hepatitis, autoimmune hepatitis, hemochromatosis, drug (toxic) liver injury, alpha-1 antitrypsin deficiency, Wilson disease, celiac disease.
AST is predominantly elevated: alcoholic liver disease (usually AST: ALT>2), cirrhosis, non-liver disease (hemolysis, myopathy, thyroid disease, exercise).
Cholestasis type
ALP+GGT+bilirubin is elevated more than AST and ALT.
Hepatobiliary causes: bile duct obstruction, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), drug-induced cholestatic liver injury, infiltrative diseases (sarcoidosis, amyloidosis, lymphoma, etc.), cystic fibrosis, liver metastasis, cholestasis.
Non-hepatobiliary causes of elevated ALP: bone disease, pregnancy, chronic renal failure, lymphoma or other malignancy, congestive heart failure, childhood growth, infection, or inflammation.
Enzymes that reflect liver cell damage
Aminotransferases, including AST and ALT, are markers of liver cell damage. AST and ALT transfer amino groups from aspartic acid or alanine to ketoglutaric acid, respectively, to produce oxaloacetic acid or pyruvic acid, which is involved in the gluconeogenesis process.
AST and ALT features
AST is found in cytoplasmic and mitochondrial isoenzymes and can be monitored in the liver, myocardium, skeletal muscle, kidneys, brain, pancreas, lungs, white blood cells, and red blood cells, and its levels are not specific for the diagnosis of liver disease. ALT is a cytoplasmic enzyme that is present in high concentrations in the liver.
Elevation of ALT and AST in serum is associated with the abundance of transaminases or changes in cell permeability in injured cells, and when hepatocyte damage occurs, transaminases activity in plasma increases.
Enzymes that detect cholestasis
Alkaline phosphatase (ALP) is a collective term for zinc-containing metalloenzymes that are highly concentrated in capillary bile ducts and other tissues (e.g., bone, intestine).
γ-glutamyltransferase (GGT) is located on cell membranes with high secretory or absorption activity. Its main function is to catalyze γ-glutamine peptides (such as glutathione [GSH]) to transfer γ-glutamyl groups into L-amino acids and other peptides. GGT is also abundant in other organ tissues (such as kidneys, pancreas, intestine, and prostate), and although GGT is less active in the liver than in the kidneys and other tissues, the GGT in serum is mainly derived from the liver.
Liver biosynthetic function test
albumin
Albumin is synthesized in the liver, about 15 grams per day. Any liver disease that causes a decrease in albumin synthesis decreases serum albumin. If liver function is normal and serum albumin levels are low, this may be associated with inadequate protein intake (malnutrition, malabsorption) or protein loss (nephrotic syndrome, protein-loss bowel disease).
Prothrombin time (PT)
PT refers to the time it takes to add an excess of tissue thromboplastin and calcium ions to a platelet-deficient plasma, and the prothrombin is converted into thrombin, causing the plasma to coagulate. This exogenous coagulation pathway requires the involvement of coagulation factors II,V., VII., and X., all of which are synthesized by the liver, so PT can reflect the liver's synthetic function, reserve function, lesion severity, and prognosis to some extent. If the liver is functionally synthetic and PT is delayed, oral anticoagulant therapy, diffuse intravascular coagulation (DIC), or vitamin K deficiency may be suggested.
Diagnostic tests for liver disease
Alcoholic liver disease
Alcoholic liver disease may be suspected if the AST < 400 IU/L and AST:ALT >2, and if the ratio above is >3, alcoholic liver disease is highly suggestive.
Drug-induced liver injury
Drugs that may cause elevated LFTs include: NSAIDs, antibiotics, statins, antiepileptics, antituberculous drugs, biologics, and some herbal medicines. Drug-induced liver injury often requires discontinuation to observe whether liver biochemical markers have fully recovered.
viral hepatitis
Any acute hepatitis virus can cause elevated LFTs. Therefore, serum antibodies to hepatitis A, B, C, D, and E should be checked. Many other viruses, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV), can also cause hepatitis.
Autoimmune hepatitis
Autoimmune hepatitis is a chronic disease characterized by persistent inflammation and necrosis of liver cells and can progress to cirrhosis. Usually AIH is more common in women than in men (4:1). Patients usually present with unexplained elevations in LFTs. Diagnosis can be made by characteristic serological markers, including antinuclear antibodies, anti-smooth muscle antibodies, and, less commonly, anti-hepatic/renal microsomal antibodies or anti-soluble liver antigen antibodies.
Nonalcoholic fatty liver disease (NAFLD)
Individuals with mildly elevated AST/ALT levels should be highly considered for NAFLD. Unlike alcoholic liver disease, ALT of NAFLD is generally higher than AST levels, and aminotransferases rarely > 300U/L, but ALT and AST do not have a unique pattern of elevation.
Wilson's disease
Wilson's disease is a rare autosomal recessive disorder characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson's disease can cause liver, nerve, and/or psychiatric manifestations. Liver manifestations are diverse, including hepatosplenomegaly, liver enzyme abnormalities, cirrhosis, and acute liver failure.
All patients with persistently elevated AST/ALT should be considered for screening for this disease with serum ceruloplasmin testing. If ceruloplasmin levels are low, K-F corneal pigment ring screening can be done with 24 h urine copper and/or serum copper levels, slit lamps, and liver biopsy if necessary.
Alpha1-antitrypsin deficiency
Alpha-1 antitrypsin deficiency is a genetic metabolic disorder common in children that can cause pan-acinar emphysema, chronic obstructive pulmonary disease, and progressive liver disease, cirrhosis, and hepatocellular carcinoma. Screening for this disease should be considered in all patients with persistent AST/ALT abnormalities, including quantitative alpha-1 antitrypsin testing and genotyping of PiZZ mutations.
【Reference】
[1] Vasimahmed Lala; David A. Minter. Liver Function Tests. StatPearls. April 29, 2019.
Yang Yating, Yan Li, et al. Excerpt from the 2016 American Society of Gastroenterology Clinical Guidelines: Evaluation of Abnormal Liver Biochemical Indexes. Journal of Clinical Hepatobiliary Diseases. Apr, 2017.
Source: Medical Pulse Tong Liver Department
Edited by: Yeah Reviewer: Xiao Ran