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The Liver - Part 3: investigations of liver function

VOL: 101, ISSUE: 50, PAGE NO: 24

Helen L. Day, MSc, BSc, RGN, RSCN, DipN, is paediatric critical care clinical educator and outreach facilitator

Rachel M. Taylor, MSc, RGN, RSCN, DipRes, is nurse researcher; both at the Paediatric Liver Centre, King’s College Hospital, London

Part 3 outlines blood tests (Malarkey and McMorrow, 2000; Siconolfi, 1995) and more complex tests.

Part 3 outlines blood tests (Malarkey and McMorrow, 2000; Siconolfi, 1995) and more complex tests.

Blood tests
Alanine aminotransferase (ALT) is found in hepatocytes but enters the bloodstream after injury or necrosis. It is used to detect hepatocellular injury, especially acute hepatitis (normal ranges: infant-60 years 15-35iu/L; 0-1 year 13-45iu/L). Alkaline phosphatase (ALP) is found in hepatocytes. Elevated serum concentration results from interference with hepatic excretion, although isolated elevation can be present in bone disorders (normal range: <600iu/L). Alpha1-fetoprotein (AFP) elevates due to hepatic regeneration in liver disorders. Also used as a marker of tumour activity and is the primary diagnostic test of hepatocellular carcinoma (normal range: <10mcg/L). Alpha1-antitrypsin is a protease inhibitor mainly produced in the liver. Alpha1-antitrypsin deficiency may cause liver disease (normal lower range: 80mg/dL). Ammonia is elevated in hepatic cell failure as a result of a decrease in protein metabolism. It can be a first sign of rare inborn errors of metabolism affecting the urea cycle (normal ranges: neonate 64-107mcmol/L; child 21-50mcmol/L; adult 11-32mcmol/L). Aspartate aminotransferase (AST) is an intracellular enzyme that increases in minor cell injury and indicates hepatitis in liver disease (normal range: 10-50iu/L). Bilirubin in its unconjugated form is usually a result of excessive haemolysis of red blood cells or an enzyme deficiency, but a rise in conjugated bilirubin is usually a result of an obstruction in bile flow (cholestasis) (normal ranges: total 3-20mcmol/L; conjugated <3.4mcmol/L; unconjugated <19mcmol/L). Bile salts are synthesised and conjugated in the liver and secreted in bile. High serum bile salt concentration can indicate an abnormality in the hepatobiliary system (normal range: total <14mcmol/L). Caeruloplasmin is a copper-binding protein that is reduced in Wilson’s disease and acute liver failure (normal range <0.2g/L). g-Glutamyl transpeptidase (GGT) is not a useful diagnostic measure on its own, but in those patients with known hepatic dysfunction it can indicate deterioration. It tends to rise with ALP as both are situated in the canaliculi borders (normal range: 5-55iu/L). Hepatitis A, B and C - The presence of core antibodies, surface antibodies and surface antigens that are associated with these viral infections, and levels of immunoglobulins IgM and IgG, indicate the presence and progression of hepatitis (Narbey, 2005). Prothrombin time (PT) relates to the ability to initiate the clotting process. A prolonged PT that is corrected with vitamin K indicates cholestatic-related vitamin K deficiency without marked hepatocellular impairment. But if it does not normalise, this denotes severe intrahepatic disease (normal range: 0-6 months 13-18 seconds; 6 months 10-13 seconds). International normalised ratio (INR) - Variations between laboratories for the control time for PT caused difficulties when making comparisons, so the INR was developed utilising the PT when applied to an index. INR (PTs) are the best indicators of synthetic liver function (normal range: 0.8-1.2). Platelets are produced in bone marrow. Approximately two-thirds are present in the circulation, the remainder being stored in the spleen. Thrombocytopenia often occurs in conjunction with portal’ hypertension, due to increased destruction and storage in the spleen related to hypersplenism (normal range: 150-450 x 109/L). Serum proteins - Albumin and globulins are synthesised in the liver. Serum total protein levels can give an indication of globulin concentrations when albumin concentration is deducted (normal range: albumin 35-50g/L; total protein 60-80g/L).

Urine tests
Urine tests can measure several components of urine (Malarkey and McMorrow, 2000; McFarlane et al, 2000). 24-hour copper excretion - The diagnosis of Wilson’s disease (inability to effectively metabolise copper) is aided by measuring urine copper concentrations before and after penicillamine (Taylor and Dhawan, 2001). While it is an indicator of Wilson’s disease, copper excretion can also be elevated in cholestasis, sclerosing cholangitis, chronic active hepatitis and nephrotic syndrome (normal range <1.25mcmol/24 hours). Urinalysis - Dark yellow or orange urine can indicate bile. Two urinalysis tests are specific to liver disease: - Bilirubin: increased levels can occur in different forms of liver disease such as obstructive jaundice, hepatitis or cirrhosis; - Urobilinogen: raised levels occur with increased haemoglobin catabolism, increased enteric production of urobilinogen and increased production and reabsorption of urobilinogen and reduced uptake by the enterohepatic circulation. In obstructive jaundice no urobilinogen is expected in either the urine or gut.

Radiological investigation
Radiological investigation can show the presence and extent of liver damage (Sherlock and Dooley, 1997). Abdominal X-ray is useful for showing opaque stones and calculi in the biliary tract (see 2). Ultrasound is useful for detecting cysts, abscesses and strictures in the vessels as it detects structures as small as 1-2mm. Doppler facilities also enable blood flow and velocity to be calculated (see 3). Angiography uses an arterial injection of contrast medium to visualise the lumens of liver arteries. Radiographic images are taken with fluoroscopy and X-ray to highlight the abnormality. Endoscopic retrograde cholangiopancreatography (ERCP) - This involves the endoscopic cannulation of the papilla of Vater in the duodenum to gain access to the bile and pancreatic ducts. It is used to establish causes of biliary problems, remove obstructions in the biliary system and precisely delineate anatomy for surgery. Percutaneous transplenic cholangiogram (PTC) is used to clear obstruction or to determine the patency of the portal vein.

Nuclear scans
Specialist nuclear scans include: positron emission tomography; hepatoiminodiacetic acid scan and magnetic resonance cholangiopancreatography (MRCP) (Villamil and Zingale, 2000).

Liver biopsy
Histological examination of the liver tissue can aid diagnosis and provide information about the severity of liver disease (see 1).

Other investigations
Various alternative tests can be useful (Sherlock and Dooley 1997; Howdle 2000). Eye tests: Kayser-Fleischer (KF) rings are pigmented corneal rings caused by an accumulation of copper. They also serve as a diagnostic feature of Wilson’s disease, but can also be present with prolonged cholestasis. KF rings are usually absent in children <10 years and difficult to see in green/brown eyes. Faecal fat: the definitive test for steatorrhoea (normal range: breastfed infant <1g/24 hours; <6 years <2g/24 hours; 6 years <4g/24 hours). - This article has been double-blind peer-reviewed. For related articles on this subject and links to relevant websites see

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