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Liver function tests and functional

tests of liver, ultrasound, biopsy

Liver Function Tests (LFT’s) These tests can be used to (1) detect the presence of liver disease (2) distinguish among different types of liver disorders (3) gauge the extent of known liver damage (4) follow the response to treatment. they suggest a general category of liver disease. such as hepatocellular or cholestatic. Liver tests have shortcomings • They can be normal in patients with serious liver disease and abnormal in patients with diseases that do not affect the liver • Liver tests rarely suggest a specific diagnosis. and will help to decide whether the disease is acute or chronic . rather.

or the findings are persistently abnormal on serial determinations.The Battery of Blood Tests • • • • To increase both the sensitivity and the specificity of laboratory tests in the detection of liver disease.prothrombin time When more than one of these tests provide abnormal findings. . When all test results are normal. the probability of missing occult liver disease is low. it is best to use them as a battery. the probability of liver disease is high. Those tests usually employed in clinical practice include: – bilirubin – Aminotransferases (ALT and AST) – alkaline phosphatase – Albumin – +/.

Our Patients Results • Albumin = 36 g/l (Ref range 35-45 g/l) Bilirubin(Total) = 38 umol/l (Ref range 0-17 umol/l) AlkP = 142 Units/l (Ref range 35-100 Units/l) GGT = 240 Units/l (Ref range 0-50 Units/l) ALT = 85 Units/l (Ref range 0-35 Units/l) AST = 160 Units/l (Ref range 0-42 Units/l) • Coagulation profile: Prothrombin time = 14 sec (Ref range 8-13s) APTT = 40 sec (Ref range 25-38s) Plasma Fibrinogen = 3.5-4.0 g/L) .3 g/l (Ref range 1.

ie increase in blood indicates damage or death of hepatocytes ALT is the more specific to the liver The pattern of the aminotransferase elevation can be helpful diagnostically. An AST:ALT ratio > 2:1 is suggestive while a ratio > 3:1 is highly suggestive of alcoholic liver disease. the ALT is higher than or equal to the AST.Whats What??? Enzymes that reflect damage to Hepatocytes: – Serum Aspartate aminotransferase (AST) – Serum alanine aminotransferase (ALT) – Serum lactate dehydrogenase (LDH) All cytosolic heptocellular enzymes. In most acute hepatocellular disorders. The AST in alcoholic liver disease is rarely >300 U/L and the ALT is often normal. . A low level of ALT in the serum is due to an alcohol-induced deficiency of pyridoxal phosphate.

In combination raised GGT can help determine if raised alkaline phosphatase elevations are due to liver disease Alkaline phosphatase and 5'-nucleotidase are found in or near the bile canalicular membrane of hepatocytes. GGT elevation in serum is less specific for cholestasis than are elevations of alkaline phosphatase or 5'-nucleotidase. while GGT is located in the endoplasmic reticulum and in bile duct epithelial cells. also can reflect hepatocyte damage. Reflecting its more diffuse localization in the liver. GGT is not specific for cholestasis. .Enzymes that Reflect damage to Bile Canaliculi: – alkaline phosphatase – 5'-nucleotidase – -glutamyl transpeptidase (GGT) Alkaline phosphatase can be elevated in many other conditions.

• Indicators of biliary excretory function: – Serum Bilirubin • Total (conjugated and unconjugated) • Direct: conjugated • Urine Bilirubin .

and X. the serum albumin is not a good indicator of acute or mild hepatic dysfunction. . measurement of the clotting factors is the single best acute measure of hepatic synthetic function and helpful in both the diagnosis and assessing the prognosis of acute parenchymal liver disease. only minimal changes in the serum albumin are seen in acute liver conditions such as viral hepatitis. Hypoalbuminemia is more common in chronic liver disorders such as cirrhosis and usually reflects severe liver damage and decreased albumin synthesis.• Indicators of Hepatocyte Function: – Proteins secreted into blood • Serum albumin • Clotting factors ( prothrombin time) Serum albumin is synthesized exclusively by hepatocytes. Because of their rapid turnover. Useful for this purpose is the serum prothrombin time. and X depends on vitamin K. which collectively measures factors II. Biosynthesis of factors II. Their serum half-lives are much shorter than albumin. and obstructive jaundice. albumin levels < 3 g/dL should raise the possibility of chronic liver disease With the exception of factor VIII. V. VII. ranging from 6 h for factor VII to 5 days for fibrinogen. drug-related hepatoxicity. Because of this slow turnover. the blood clotting factors are made exclusively in hepatocytes. The prothrombin time may be elevated in hepatitis and cirrhosis as well as in disorders that lead to vitamin K deficiency such as obstructive jaundice or fat malabsorption of any kind. VII. IX.

Patients with advanced liver disease typically have significant muscle wasting. primarily those in the colon. . which is excreted by the kidneys. The liver plays a role in the detoxification of ammonia by converting it to urea. which is combined with glutamic acid to form glutamine. which likely contributes to hyperammonemia in these patients. Striated muscle also plays a role in detoxification of ammonia.• Indicators of Hepatocyte Metabolism – Blood Ammonia – Ammonia is produced in the body during normal protein metabolism and by intestinal bacteria.

genetic testing for HFE gene mutations autoimmune markers – to diagnose primary biliary cirrhosis (antimitochondrial antibody. PANCA). increased hepaticcopper level Elevated iron saturation and serum ferritin. AMA). sclerosing cholangitis (peripheral antineutrophil cytoplasmic antibody. smooth-muscle. and autoimmune hepatitis (antinuclear. and liver-kidney microsomal antibody) Serum Vitamin levels – not only in bile responsible for the absortption of fat-souble vitamins. the liver is respobsible for storage of all vitamins including water-soluble . phenotypes PiZZ or PiSZ Decreased serum ceruloplasmin and increased urinary copper.Other laboratory tests • • • • • • hepatitis serology to define the type of viral hepatitis Reduced a1 antitrypsin levels.

and extra-hepatic cholestasis (Obstructive jaundice) Both fractions may be elevated Bilirubinuria Normal to moderate elevation Rarely >500 IU Elevated. often >4 times normal elevation Fractionate. will correct with parenteralvitamin K Infiltrative diseases (tumor. often >4 times normal elevation N Normal If prolonged. hepatotoxins. partial bile duct obstruction Usually normal Normal to slight elevation Elevated. If >5X above control and not corrected by parenteralvitamin K. often >500 IU ALT >AST Normal to <3 times normal elevation N Usually normal. but usually <300 IU Normal to <3 times normal elevation low Often prolonged Fails to correct with parenteralvitamin K Alcoholic hepatitis Cirrhosis Both fractions may be elevated Bilirubinuria AST:ALT > 2 suggests alcoholic hepatitis or cirrhosis Normal to <3 times normal elevation low Often prolonged Fails to correct with parenteralvitamin K Intra. granulomata). suggests po prognosis Chronic hepatocellular disorders Both fractions may be elevated Bilirubinuria Elevated. or confirm liver origin with 5' nucleotidase or glutamyl transpeptidase N Normal .Type of Disorder Bilirubin Aminotransfera ses Alkaline Phosphatase Albu min Prothrombin Time Hemolysis/Gilbert's syndrome Normal to 86 mol/L (5 mg/dL) 85% due to indirect fractions No bilirubinuria Normal Normal N Normal Acute hepatocellular necrosis (viral and drug hepatitis. acute heart failure) Both fractions may be elevated Peak usually follows aminotransf erases Bilirubinuria Elevated.

It shows – – – – – • dilation of intrahepatic or extrahepatic biliary tree Gallstones Steatosis space-occupying lesions within the liver (enables the clinician to distinguish between cystic and solid masses) Doppler imaging can detect the patency of the portal vein. and often two and sometimes three studies are needed before a diagnosis can be reached. The current best test for diagnosing cirrhosis is liver biopsy. . hepatic artery. ascites. Radiographic studies that strongly suggest cirrhosis include a small. or portal and hepatic vein thrombosis.Imaging • Ultrasound is the first diagnostic test to use. intra-abdominal varices. however. splenomegaly. and hepatic veins and determine the direction of blood flow CT and MRI are indicated for: – – – – identification and evaluation of hepatic masses staging of liver tumours preoperative assessment. With regard to mass lesions. no test is considered a diagnostic gold standard. sensitivity and specificity remains a problem. nodular liver.

methods using elastrography have been developed to measure hepatic stiffness as a means of assessing hepatic fibrosis.• • • • Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are the procedures of choice for visualization of the biliary tree. (Through the endoscope. Nuclear Medicine Scans: show gallbladder filling and emptying. insertion of drains into hepatic abscesses. then can watch empty. and creation of vascular shunts in patients with portal hypertension. excreted by bile ie. accumulated in gallbladder. measurement of portal pressure. infusion of CCK. the physician can see the inside of the stomach and duodenum. US elastrography is now undergoing evaluation for its ability to detect different degrees of hepatic fibrosis and to obviate the need for liver biopsy in assessing disease stage. Inject radioactive dye. and inject dyes into the ducts in the biliary tree and pancreas so they can be seen on xray) Recently. Interventional radiologic techniques allow the biopsy of solitary lesions. .

and in monitoring response to treatment Biopsy of the liver is a safe procedure that can be easily performed at the bedside with local anesthesia. Liver biopsy is most accurate in disorders causing diffuse changes throughout the liver and is subject to sampling error in focal infiltrative disorders such as hepatic metastases. Cirrhosis is identified by histopathologic examination of the liver In selected instances. liver biopsy is necessary for diagnosis but is more often useful in assessing the severity (grade) and stage of liver damage. in predicting prognosis. Liver biopsy is of proven value in the following situations: (1) hepatocellular disease of uncertain cause (2) prolonged hepatitis with the possibility of chronic active hepatitis (3) unexplained hepatomegaly (4) unexplained splenomegaly (5) hepatic filling defects by radiologic imaging (6) fever of unknown origin (7) staging of malignant lymphoma. Liver biopsy should not be the initial procedure in the diagnosis of cholestasis. . although no method is suitably accurate in demonstrating underlying cirrhosis.Percutaneous biopsy • • • There have been great advances made in hepatic imaging.