RR School Of Nursing

Liver Enzymes

There are multiple biochemical tests commonly referred to as liver enzymes, but for the purposes of this chapter we will discuss only those that are readily available and used in routine clinical practice. Biochemical liver tests can be summarized as those that reflect injury and those that reflect synthetic or excretory function. This text will refer to liver function tests (LFTs) as those tests that reflect the latter, and will not refer to the enzymes that generally reflect injury, the aminotransferases. The most commonly used liver tests are bilirubin, alkaline phosphatase, and the aminotrans-

ferases. other less commonly used but useful tests are y-glutamyl transpeptidase (GGT), 5'-nucleotidase (5'NT), albumin, and prothrombin time (PT). Aminotransferase tests are for aspartate aminotransferase (AST), formerly serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT), formerly serum glutamic pyruvic transaminase, both of which participate in hepatic glu-coneogenesis. Leakage of these enzymes into serum occurs with hepatocyte injury and death. Whereas ALT is quite liver specific, AST is not and is also commonly found in skeletal and cardiac muscle tissue. A more complete description of each is given in Tables 104-1 and 104-2.

The aminotransferases are generally reflective of parenchymal liver injury, such as that seen with viral hepatitis, medication or toxin-induced injury, autoimmune hepatitis, and several infiltrative disorders, such as hemochromatosis, Wilson's disease, a-1-antitrypsin deficiency, and fatty liver disease. Of course, in some of these conditions, alkaline phosphatase and GGT can be elevated to some extent as well, but bilirubin is not elevated unless there is obstruction to bile flow or significant liver dysfunction or injury.

Alkaline phosphatase is a ubiquitous enzyme often elevated in disorders of the biliary tract, but can also be mildly elevated in various liver diseases primarily involving the parenchyma, possibly as a result of injury to small bile ducts. It can also be elevated as a result of normal physiology in pregnancy and childhood, and in pathologic bone conditions. Interestingly, alkaline phosphatase does not always rise immediately with bile duct obstruction. Elevations are not simply a "backwash" of the enzyme into the serum, but rather require upregulation of messenger ribonucleic acid for increased production of alkaline phos-phatase in response to bile duct epithelial injury.

GGT is an ubiquitous enzyme found in many organs including brain, intestine, heart, kidney, and the liver, but importantly not found in bone. Hence, its elevation suggests alkaline phosphatase elevation is not of bone origin. A more specific, but rarely used test is for 5'NT, which is also found in several organs but only released into plasma by the liver when injured. Hence, its elevation is very specific to the liver.

Bilirubin can be elevated for a myriad of reasons, some attributable to liver excretory dysfunction or significant

TABLE 104-1. Enzymes Reflecting Liver Injury
Lab Test	Physiologic Function	Source	Commonly Associated	Of Note	Pitfalls
			Liver Abnormalities
AST	Catalyzes transfer of aminogroup	Liver, heart, kidney,	Viral hepatitis,	AST/ALT ratio > 2 typically	May be normal viral
	from aspartic acid to ketoglutaric	pancreas,brain,	alcohol liver injury,	due to alcohol injury.	hepatitis or with
	acid to produce oxaloacetic acid	RBC, WBC	ischemichepatic injury,	AST/ALT > 1 also seen	advancing fibrosis.
			drug induced hepatitis,	in cirrhosis. ALT rarely	Falsely low with dialysis.
ALT	Catalyzes transfer of amino group	Liver	fatty liver disease,	> 300 U/L in chronic	Poor correlation with
	from alanine acid to ketoglutaric		Wilson's disease,	conditions.	degree of liver necrosis in
	acid to ketoglutaric produce		celiac disease,		acute setting.
	pyruvic acid		a-1-Antitrypsin deficiency

LDH	Catalyzes interconversion	Heart, liver, kidney, Several isoenzymes which can be measured.
	of lactate and pyruvate	muscle, brain, blood Poor specificity for liver disease,
		cells, lungs, necrotic and not useful overall.
		conditions, infiltrative
		disorders, hemolysis,
		muscle injury,
		malignancies

ALT = alanine aminotransferase; AST = aspartate aminotransferase; LDH = lactate dehydrogenase; RBC = red blood cells; WBC = white blood cells.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; LDH = lactate dehydrogenase; RBC = red blood cells; WBC = white blood cells.

liver injury, and at other times, not related to the liver at all. The most important reasons for bilirubin elevation are obstructive disorders of bile flow and hepatic dysfunction, which may be mild or indicative of liver failure. The latter is generally accompanied by other signs, including cognitive and psychomotor dysfunction and coagulation disorders. Liver related disorders such as congenital hyperbilirubinemias (Tables 104-2 and 104-3) are characterized by bilirubin abnormalities due to enzyme deficiencies but are not reflective of liver failure or synthetic dysfunction per se.

A general scheme of the proper workup and diagnosis of disorders associated with patterns of liver disease is outlined in Figure 104-1. Although this is simplified, it does reflect the thought process one should have when assessing elevated enzymes. The old axiom of rechecking abnormal enzymes to confirm chronicity holds true, but enzymes are rarely spuriously elevated without some underlying pathology, even if the pathology is transient, such as idiosyncratic medication-induced injury. Occasionally enzymes may be elevated with systemic disease and not reflect underlying liver disease, but these situations are generally understood because of other

AST/ALT

Bilirubin alone

Alkaline phos ± bilirubin

Mixed

Fractionate bilirubin

Conjugated

Ultrasonography

Ultrasonography

Biliary tract dilation

History specific tests/serology

Unconjugated

Evaluate for hemolysis

Normal

Check AMA

Biliary tract dilation

ERCP

Mass

Liver biopsy.

CT/MRI

FIGURE 104-1. A general scheme of the proper workup and diagnosis of disorders associated with patterns of liver disease. ALT = alanine aminotransferase; AST = aspartate aminotransferase; CA = cancer antigen; CEA = carcinoembryonic antigen; CT = computed tomography; ERCP = endoscopic retrograde cholangiography; MRI = magnetic resonance imaging.

TABLE 104-2. Liver Tests Reflecting Cholestasis and Biliary Tract Disorders

Laboratory	Physiologic Function	Source	Commonly Associated	Of Note	Pitfalls
Test			Liver Abnormalities
Bilirubin,	Bilirubin glucoronide,	Liver	Liver necrosis, PBC/PSC,	Prognostically useful	Value of conjugated
conjugated	results from conjugation		cirrhosis,	in alcohol liver disease,	bilirubin may be
	of bilirubin in the liver.		intrahepatic cholestasis	PSC, PBC; Renally	overestimated with diazo
	Water soluble.		due to drugs or genetic	excreted, so rarely	method of measurement;
			abnormality, sepsis,	> 30 mg/dL with	Often elevated in sepsis
			bilary tract obstruction	normal renal function	or postoperative
					situations in setting
					of no liver disease
Bilirubin,	Organic anion from	RBC	Hemolysis	Sustained hemolysis will not
unconjugated	hemoglobin degradation.	breakdown	Physiologic	result in value > 5 mg/dL
	Lipid soluble	Defects in	jaundice of newborn	in setting of normal liver
		hepatic conjugation	Inherited defects of	function
		or uptake	bilirubin uptake
Alkaline	Group of glycoprotein	Liver, bone,	Cholestatic liver diseases	Coded by four genes	Multiple sources; Exact
hosphatase	isoenzymes that catalyze	kidney, intestines,	Obstruction of bile flow	Immunologically distinct	physiologic function not
	hydrolysis of phosphate esters	placenta, cancers,	Infiltrative disorders of liver	Found on plasma membranes	clear; Degree of elevation
		WBCs	Malignancies	Elevations due primarily to	often does not correlate
				increased synthesis in	with clinical finding
				obstructive liver disease, not
				impairedexcretion in bile
GGT	Catalyzes transfer of y-glutamyl	Liver, spleen,	Cholestatic liver disease,	Membrane associated and found Found in many tissues
	groups of peptides to other	kidney, brain,	alcohol injury, biliary tract	in biliary tree; Catalyzes	Sometimes not elevated
	amino acids	heart, lung,	disease	metabolism of glutathione	with alkaline phosphatase
		pancreas, seminal		conjugates with some	in liver disease
		vesicles		xenobiotics	Elevated with alcohol
					use in some patients and
					with certain medications
5'NT	Catalyzes hydrolysis of	Liver, intestines,	Cholestatic disease	Physiologic significance not	Not readily available
	nucleotides by releasing	brain, heart,	where alkaline phosphatase	known; Although found in	through all laboratories
	phosphate from pentose ring	vascular tissue,	is elevated	several tissues, only released
		pancreas		from plasma membranes of
				hepatobiliary tissue with injury

GGT = y-glutamyl transpeptidases; 5'NT = 5' nucleotidase; PBC = primary biliary cirrhosis; PSC = primary sclerosing cholangitis; RBC = red blood cell; WBC = white blood cells.

GGT = y-glutamyl transpeptidases; 5'NT = 5' nucleotidase; PBC = primary biliary cirrhosis; PSC = primary sclerosing cholangitis; RBC = red blood cell; WBC = white blood cells.

TABLE 104-3. Liver Disorders and Associated Laboratory Test Abnormalities

Conjugated Bilirubin

Unconjugated Bilirubin

Alkaline Phosphatase

Aminotransferase

Hepatitis, cirrhosis, biliary Hemolysis, tract obstruction, Dubin-Johnson syndrome, Rotor's syndrome, intrahepatic cholestasis

Physiologic (pregnancy, childhood), Hepatobiliary disorders, Viral hepatitis, medications, physiologic jaundice of newborn, Gilbert's syndrome, Crigler-Najjar syndromes, medications biliary tract disease, infiltrative disease, malignancy, bone disorders pancreatitis, alcohol, renal disease, medications herbs/supplements, alcohol, autoimmune hepatitis, hemochromatosis, wilson disease, a-1-antitrypsin deficiency, endocrinologic disorders, celiac disease

GGT = y-glutamyl transpeptidases.

circumstances. In other words, enzymes should be evaluated in conjunction with a careful history and examination of the patient, the information from which is invaluable to making sense of the enzyme abnormalities. For example, in a patient with elevated aminotransferases and a history of intravenous drug use, HC is a common finding. Rechecking the enzymes several months later to see if the abnormality persists is not necessary prior to checking viral hepatitis serologies, because the risk factor for enzyme elevation has been assessed. Likewise, in an individual with newly elevated enzymes soon after beginning therapy with a known potential hepatotoxin, such as a nonsteroidal anti-inflammatory drug (NSAID) or lipid-lowering agent, the diagnosis becomes slanted in favor of drug hepatotoxicity.

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