What all is involved in the Liver “Function” Tests?
If the chief complaint of your patient is abdominal pain, altered mental status, overdose, generalized weakness chances are you at least considered ordering a hepatic panel. In fact, studies show that the hepatic panel is the third most common laboratory test ordered in the emergency department only behind the CBC and renal panel. If emergency medicine physicians are so quick to order this test, it is important to also know how to interpret all the little red arrows that often accompany your results. For this we will review each component and even (wait for it) … a little biochemistry!
Overall abnormal hepatic panel falls into three main categories:
First lets start with the markers most suggestive of hepatocellular damage:
Alanine aminotransferase also catalyzes the transfer of the amine group within the alanine cycle in which amino groups are transferred from muscle to liver. Compared to AST, ALT elevation is much more specific for the liver. ALT will also remain elevated for much longer than AST and can often take weeks to return to normal levels in the setting of acute hepatic injury. So although, elevated ALT is indicative of liver cell necrosis, the level of ALT can be hard to interpret in the acute setting but the rest of the hepatic panel can help with this.
Aspartate transaminase is an important enzyme in the Krebs cycle involved in both amino acid degradation and biosynthesis catalyzing the transfer of the nitrogenous portion of the amino acid. However, it is much less specific to the liver than its counterpart, ALT, because it is also found in heart, skeletal muscle, pancreas, kidneys, brain and red blood cells. This enzyme gets released into blood and is directly proportional to cellular damage. It will be most elevated in the acute phase of cellular necrosis.
In order to help further differentiate the etiology of ALT/AST elevation, we need to look at the other parts of the hepatic panel. One pattern of liver damage is a cholestasis pattern, which can further be extrapolated by looking at alkaline phosphatase and bilirubin levels.
Alkaline phosphatase is responsible for transferring metabolites across cell membranes, and is found in all tissues of the body. So when the ALP results return in the hepatic panel, this number is actually a compilation of over 60 enzymes that are found most prominently in the liver (specifically found in the bile canaliculus membrane) and skeletal muscle. Elevation in ALP can be associated with biliary obstruction, and will often be elevated before the rise in bilirubin. Yet, similar to AST, because ALP is not very specific for liver tissue, you can also see ALP elevation in adolescents, pregnancy, bony diseases and other non-hepatic etiology.
Bilirubin is the normal by-product of the breakdown of hemoglobin, which circulates in the blood bound to albumin and is transported to the liver for metabolism. Within the hepatocytes, bilirubin is conjugated with glucuronic acid, a process catalyzed by uridine diphosphoglucuronate-glucuronyltransferase (UDP-GT). Within the hepatic panel, total bilirubin gets broken up into indirect and direct, also known as unconjugated and conjugated. It is important to note that the total serum bilirubin is not a sensitive indicator of hepatic dysfunction. Studies have shown that the actual bilirubin level can remain normal despite severe hepatic injury. To complicate things further, both indirect and direct bilirubin can be elevated in the setting of liver disease, although elevated direct bilirubin does tend to be a more sensitive indicator.
Represents the unconjugated bilirubin and in normal physiology and normal functioning liver, indirect bilirubin make up the majority of total bilirubin (80-90%). However, disease processes that result in increase rate of bilirubin production (ex. hemolysis), reduce hepatic uptake (ex. certain medications, portal shunts) or reduced rate of conjugation (ex. Gilbert’s disease) would all result in increased indirect bilirubin
Once the bilirubin gets conjugated in the liver, it then gets excreted in the bile to the duodenum. Between 10-20% of the total bilirubin represents conjugated bilirubin. Conjugated bilirubin levels remain low because it is rapidly excreted into bile and removed from the body. The main reasons you may see an abnormal elevation in your direct bilirubin include diminished hepatocyte function (ex. cirrhosis, hepatitis, or drug induced liver injury), intrahepatic obstruction (ex. cirrhosis, hepatitis) or extrahepatic obstruction (ex. gallstones, malignancy obstructed common bile duct).
Up until now, none of the above tests has actually been any indication of how the liver is functioning despite the colloquial term of “liver function tests”. The only true predictor of liver function in the hepatic panel is albumin.
The reason that albumin reflects how the liver is functioning is because albumin is synthesized directly by the liver. It is the main protein considered to make up the total protein value in the LFT results, the other main component being globulin. Low albumin can reflect the function of the liver, however it also can be low in the setting of protein wasting from the kidneys (such as in nephrotic syndrome), malnutrition or chronic inflammatory state. Adding in other factors such as PT/INR, creatinine, bilirubin collectively contribute to the scores of liver failure which are featured in Dr. Kelli Jarrell’s post.
Content by Kathryn Banning, MD
Peer Editing and Infographics by Ryan LaFollette, MD
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