Biochemical Tests

Investigations for Liver Diseases

Adequate evaluation of an infant, child or adolescent with suspected liver disease involves an appropriate and accurate history, a carefully performed physical examination and skillful interpretation of signs and symptoms. Further evaluation is aided by judicious selection of diagnostic tests followed by the use of imaging modalities or a liver biopsy.

BIOCHEMICAL TESTS
Indication:
Estimation of synthetic and excretory functions: Where there is increase in serum bilirubin (total and fractionated), prolongation of prothrombin time (PT) or international normalized ratio (INR) and decrease in albumin level. Detection of Hepatocellular Damage: Acute liver cell injury (parenchymal disease) in viral hepatitis, drug- or toxin-induced liver disease, shock, hypoxemia or metabolic disease is best reflected by marked increases in serum aminotransferase levels. Detection of biliary Disease: Cholestasis (obstructive disease) involves regurgitation of bile components into serum so the serum levels of total and conjugated bilirubin and serum bile acids are elevated. Also elevations in serum AP, 5 nucleotidase (5NT), and -glutamyl transpeptidase (GGT) levels are sensitive indicators of obstruction or inflammation of the biliary tract. Determination of the type of jaundice: Fractionation of the total serum bilirubin level into conjugated and unconjugated bilirubin fractions helps to distinguish between elevations caused by hemolysis and those caused by hepatic dysfunction. Detection of certain diseases: Patients with autoimmune hepatitis often have high gamma-globulin levels and increased titers of anti-smooth muscle, antinuclear and anti-liver-kidney-microsome antibodies. Resurgence in -fetoprotein levels may suggest hepatoma, hepatoblastoma, or hereditary tyrosinemia.

Investigations for Liver Diseases

Biochemical Tests

Interpretation:
Interpretation of results of biochemical tests of hepatic structure and function must be made in the context of age-related changes. Aminotransferases (ALT: 7-56 IU/L & AST: 5-47 IU/L): Alanine aminotransferase (ALT) is liver specific, whereas aspartate aminotransferase (AST) is derived from other organs in addition to the liver. o The most marked rises of both AST and ALT levels may occur with acute hepatocellular injury. o In acute hepatitis, the rise in ALT may be greater than the rise in AST. o In chronic liver disease or in intrahepatic and extrahepatic biliary obstruction, AST and ALT elevations may be less marked. Alkaline phosphatase (30-120 IU/L): Normal growing children have significant elevations of serum AP activity originating from influx into serum of the isoenzyme that originates in bone. Therefore, an isolated increase in AP does not indicate hepatic or biliary diseases if other liver function test results are normal. Albumin (3.5-5.3 g/dL): Albumin is a protein made specifically by the liver that can be measured cheaply and easily. It is the main constituent of plasma protein. Albumin levels are decreased in chronic liver disease such as cirrhosis. Coagulation tests (PT: 10-14 sec & INR: 0.8-1.2): The liver is responsible for the production of coagulation factors. The INR will be increased only if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired. Increased levels of INR means that blood is taking more time than usual to coagulate or clot. It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively. 5 nucleotidase and -glutamyl transpeptidase (0-42 IU/L): 5NT and GGT are increased in cholestatic conditions and may be more specific for hepatobiliary disease. Cholesterol (<200 mg/dL): Cholesterol levels may be markedly elevated in patients with intra or extrahepatic cholestasis and decreased in severe acute liver disease such as hepatitis. Serum glucose (82-110 mg/dL): Gluconeogenesis is usually the last function to be lost in the setting of fulminant liver failure. Investigations for Liver Diseases

Biochemical Tests Bilirubin (Total: 0.2-1.2 mg/dL & Direct: 0.1-0.4 mg/dL): Bilirubin is a breakdown product of heme. Bilirubin is taken up into hepatocytes, conjugated with glucuronic acid then secreted into the bile to the intestine. Increased total bilirubin (TBIL) causes jaundice, and can signal a number of problems: o Pre-hepatic: Increased bilirubin production as in hemolytic anemias and internal hemorrhage. o Hepatic: Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g., reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin) as in cirrhosis and viral hepatitis. o Post-hepatic: Obstruction of the bile ducts either within the liver or in the bile duct. The diagnosis is narrowed down by looking at the levels of direct & indirect bilirubin: o If indirect is elevated: Hemolysis, viral hepatitis or cirrhosis can be suspected. o If direct bilirubin is elevated: Bile duct obstruction by gallstones or cancer should be suspected.

URINE TEST:
Dipstick tests are available for bilirubin and urobilinogen in the urine. Bilirubinuria is due to the presence of conjugated bilirubin. It is found in the jaundiced patient with hepatobiliary disease; its absence implies that the jaundice is due to increased unconjugated bilirubin. Urobilinogen in the urine is, in practice, of little value but suggests hemolysis or hepatic dysfunction of any cause.

Investigations for Liver Diseases

Imaging Procedures

IMAGING PROCEDURES
Various techniques help define the size, shape, architecture of the liver and the anatomy of the intrahepatic and extrahepatic biliary trees.

Ultrasonography (US):
o Ultrasonography provides information about the size, composition and blood flow of the liver. o Increased echogenicity is observed with fatty infiltration; mass lesions as small as 12 cm may be shown. o US can assess gallbladder size, detect dilatation of the biliary tract and define a choledochal cyst even in neonates o In infants with biliary atresia, US findings may include small or absent gallbladder, nonvisualization of the common duct and presence of the triangular cord sign, a triangular/tubular-shaped echogenic density in the bifurcation of the portal vein, representing fibrous remnants at the porta hepatis. o In patients with portal hypertension, Doppler US can evaluate patency of the portal vein, demonstrate collateral circulation and assess size of spleen and amount of ascites. Relatively small amounts of ascitic fluid can also be detected. o The use of Doppler US has been helpful in determining vascular patency after liver transplantation.

Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI):

o CT scan or MRI is more accurate than US in detecting focal lesions such as tumors, cysts and abscesses. o When enhanced by contrast medium, CT scanning may reveal a neoplastic mass density only slightly different from that of a normal liver. o When a hepatic tumor is suspected, CT scanning is the best method to define anatomic extent, solid or cystic nature and vascularity. o In differentiating obstructive from non-obstructive cholestasis, CT scanning or MRI identifies the precise level of obstruction more frequently than US.

Angiographic Studies:
Selective angiography of the celiac, superior mesenteric or hepatic artery can be used to visualize the hepatic or portal circulation. Both arterial and venous circulatory systems of the liver can be examined. Angiography is frequently required to define the blood supply of tumors before surgery and is useful in the study of patients with known or presumed portal hypertension where the patency of the portal system, the extent of collateral circulation and the caliber of vessels under consideration for a shunting procedure can be evaluated.

Investigations for Liver Diseases

Imaging Procedures

Cholangiography:
Cholangiography, direct visualization of the intrahepatic and extrahepatic biliary tree after injection of opaque material, may be required in some patients to evaluate the cause, location or extent of biliary obstruction.

Endoscopic Retrograde Cholangiopancreatography (ERCP):

ERCP is an alternative method of examining the bile ducts in older children. The papilla of Vater is cannulated under direct vision through a fiberoptic endoscope, and contrast material is injected into the biliary and pancreatic ducts to outline the anatomy.

Magnetic Resonance Cholangiopancreatography (MRCP):

This technique involves the manipulation of a volume of data acquired by MRI. A heavily T2-weighted sequence enhances visualization of the water-filled bile ducts and pancreatic ducts to produce high-quality images of ductal anatomy. This non-invasive technique is replacing diagnostic ERCP.

Radionuclide Scanning:
Radionuclide scanning relies on selective uptake of a radiopharmaceutical agent as technetium 99m-labeled sulfur colloid and gallium 67. The 99mTc-sulfur colloid scan can detect focal lesions (tumors, cysts, abscesses) >23 cm in diameter. This modality can help to evaluate patients with possible cirrhosis and with patchy hepatic uptake and a shift of colloid uptake from liver to bone marrow. The 99mTc-substituted iminodiacetic acid dyes may differentiate intrahepatic cholestasis from extrahepatic obstruction in neonates. Imaging results are best when scanning is preceded by a 57 day period of treatment with phenobarbital to stimulate bile flow. After intravenous injection, the isotope is normally detected in the bowel within 12 hr. In the presence of extrahepatic obstruction, excretion of the isotope is delayed; accordingly, serial scans should be made for up to 24 hour after injection. Early in the course of biliary atresia, hepatocyte function is usually good; uptake (clearance) occurs rapidly, but excretion into the intestine is absent. In contrast, uptake is poor in parenchymal liver disease, such as neonatal hepatitis, but excretion into the bile and intestine eventually ensues.

Investigations for Liver Diseases

Liver Biopsy

LIVER BIOPSY
Liver biopsy combined with clinical data can suggest a cause in most cases.

Indications:
Specimens of liver tissue can be used: to provide a precise histologic diagnosis in: o o o o o o o o o o o Neonatal cholestasis. Chronic active hepatitis. Metabolic liver disease. Suspected Reye syndrome. Intrahepatic cholestasis. Congenital hepatic fibrosis. Undefined portal hypertension. Enzyme analysis to detect inborn errors of metabolism. Analysis of stored material such as iron, copper, or specific metabolites. Monitoring responses to therapy. Detection of complications of treatment with potentially hepatotoxic agents.

Approaches:
Percutaneous approach: It can be performed safely in infants as young as 1 week of age. Patients usually require only conscious sedation and local anesthesia. Open laparotomy (wedge) approach: It is done by a general surgeon. Transjugular approach: Transjugular approach is done under ultrasound and fluoroscopic guidance.

REFERENCES:
o Nelson Textbook of Pediatrics, 19th Edition. o Kumar & Clark's Clinical Medicine, 7th Edition.

BY

Dr. Mahmoud Ahmed Mahmoud Alexandria University of medicine

Investigations for Liver Diseases