Hepatobiliary System Biochemistry Tests (PDF)

NB 2234 BIOKIMIA KLINIKAL BIOCHEMISTRY TESTS OF THE HEPATOBILIARY SYSTEM  LIVER FUNCTION Liver plays an important role in protein, carbohydrate and lipid homeostasis. It can be divided into three types: Metabolic function Synthetic function Excretion and detoxification...

NB 2234 BIOKIMIA KLINIKAL BIOCHEMISTRY TESTS OF THE HEPATOBILIARY SYSTEM  LIVER FUNCTION Liver plays an important role in protein, carbohydrate and lipid homeostasis. It can be divided into three types: Metabolic function Synthetic function Excretion and detoxification  General Metabolic Function ▪ Glucose to Glycogen ▪ Glycogenolysis ▪ Gluconeogensis ▪ Carbon skeletons of fatty acids transported to adipose tissue as very low-density lipoprotein (VLDL) ▪ Fatty acids reaching the liver from fat stores may be metabolized in the tricarboxylic acid cycle, converted to ketones or incorporated into triglycerides  Synthetic functions ▪ Plasma proteins ▪ Most coagulation factors, Including fibrinogen, factor II (prothrombin), V, VII, IX, X, XI, XII, and XIII ▪ Primary bile acids ▪ Lipoproteins: VLDL, HDL  Excretion and Detoxification ▪ Cholesterol ▪ Unchanged ▪ Bile acids ▪ Amino Acids ▪ Deamination, amino group and the ammonia produced by intestinal bacterial action converted to urea ▪ Steroid Hormones: Metabolized and inactivated by conjugation with glucuronate and sulphate ▪ Many drugs which are metabolized and inactivated by enzymes of the endoplasmic reticulum system ▪ Toxins: the reticuloendothelial Kupffer cells in the hepatic sinusoids are well placed to extract toxic substances  Excretion and Detoxification Efficient excretion of the end products of metabolism and of bilirubin depends on: – Normally functioning liver cells – Normal blood flow through the liver – Patent biliary ducts  Liver Function Tests Groups of Clinical Biochemistry Laboratory blood assays designed to give information about the state of a patient’s liver. Most liver diseases cause only mild symptoms initially, but it is vital that these diseases be detected early. Noninvasive method of screening for the presence of liver dysfunction. This testing performed on a patient’s serum or plasma samples obtained by phlebotomy. Interpretation must be performed within the context of the patient’s risk factors, symptoms, concomitant conditions, medications, and physical findings. Some of these tests are associated with functionality, some with cellular integrity and some with conditions linked to the biliary tract.  Liver Function Tests Liver function tests are used to aid in: 1. Diagnosing 2. Differential diagnosis 3. Evaluating severity, and allow the prediction of outcome 4. Monitoring therapy: evaluate response to treatment, and adjust treatment when necessary 5. Assessing the prognosis of the liver disease and dysfunction Liver Function Tests Liver Function Test Normal values (range)  Liver Function Test Mild Moderate Marked (times) (times) (times) AST 20 ALT 20 ALP 5 GGT 10 Mild elevation is nonspecific and usually normal when repeated observe vs. additional evaluation must be made in context of clinical scenario  Liver Function Test Advantages Disadvantages sensitive, noninvasive lack sensitivity method of screening liver – normal results in serious liver dysfunction disease pattern of laboratory test not specific for liver abnormalities to recognize dysfunction type of liver disorder assess severity of liver seldom lead to specific dysfunction diagnosis follow cause of liver disease  Liver Function Test Classified into 3 groups synthetic function : albumin, PT hepatocyte injury : AST, ALT cholestasis : bilirubin, ALP, GGT PT, albumin, bilirubin-most common tests used as prognostic factors  Liver Function Tests ▪ Total bilirubin (TBIL): Bilirubin is a breakdown product of heme. The liver is responsible for clearing the blood of bilirubin (2-14 µmole/L). Total bilirubin might be increased by the following drugs: Anabolic Steroids Antibiotics Antimalarials Ascorbic Acid Diabinese Codeine Diuretics Epinephrine Oral contraceptives Vitamin A ▪ Direct bilirubin: elevated in bile duct obstruction by gallstones or cancer should be suspected (0-4 µmole/L).  Liver Function Tests Alanine transaminase (ALT): is an enzyme necessary for energy production. It is present in a number of tissues including the liver (hepatocytes), heart and skeletal muscles it rises dramatically in acute liver damage, such as viral hepatitis or paracetamol overdose (5-40 IU/L). Drugs that may increase ALT levels: – Acetaminophen – Ampicilline – Codeine – Dicumarole – Indomethacine – Methotrexate – Oral contraceptives – Tetracyclines – Verapamil Aspartate transaminase (AST): enzyme involves in energy production. it is raised in acute liver damage, but is also present in red cells, cardiac and skeletal muscle, and is therefore not specific to the liver (10-40 IU/L). – ALT in conjuction with AST helps to distinguish between heart damage and liver tissue damage  ALT and AST < 5 times ALT predominant AST predominant Chronic hepatitis B, C Alcohol-related liver injury Acute hepatitis (A-E, EBV, Steatohepatitis CMV) Cirrhosis Steatohepatitis Hemochromatosis Drug Medications/toxins Nonhepatic Autoimmune hepatitis – Hemolysis – Myopathy Alpha1-antitrypsin deficiency – Thyroid disease Wilson’s disease – Strenuous exercise Celiac disease Macro AST *almost any types of liver disease  ALT and AST > 15 times Acute viral hepatitis (A- Autoimmune hepatitis E, herpes) Wilson’s disease Medications/toxins Acute Budd-Chiari Ischemic hepatitis syndrome Acute bile duct obstruction Hepatic artery ligation Heat stroke ▪AST predominate : medication/toxin, ischemic ▪ >75 times : ischemic, toxic, viral (less common)  Liver Function Tests Alkaline phosphatase (ALP): It mainly comes from liver, bone and placenta. In the liver it is in the cells lining the biliary ducts. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver (30-120 IU/L). Gamma glutamyl transpeptidase (GGT): Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, it may be elevated with even minor, sub-clinical levels of liver dysfunction. It is raised in alcohol toxicity acute and chronic (2-30 IU/L). Drugs that may cause increased GGT levels: – Alcohol – Phenytoin – Phenobarbital » GGT level is compared with ALP level to distinguish between skeletal disease and liver disease  Liver Function Tests Lactate Dehydrogenase (LDH): is an enzyme found in many body tissues, including liver. Elevated levels of LDH may indicate liver damage Coagulation Tests (prothrombin time, PT): It is not a sensitive measure of liver function Albumin (Alb): it is made specifically by the liver. – Its level decreased in chronic liver diseases such as cirrhosis (3.2-5.4 g/L). – not reliable indicator of acute liver disease  Liver Function Tests Prothrombin time (PT) – liver synthesize coagulation factor except FVIII – most present in excess, clotting abnormal occur only when substantial impairment in ability of liver to synthesis – PT : FI, II, V, VII, IX and X – T1/2 FVII 6 hrs. (shortest) – prognosis : acute, chronic hepatocellular disease prolonged : vitamin K deficiency (malnutrition, malabsorption, antibiotics) massive transfusion congenital disease liver disease warfarin DIC  Liver Function Tests – Ammonia: a breakdown product of protein that is normally converted into urea by the liver. Analysis of blood ammonia aids in the diagnosis of sever liver diseases and helps to monitor the course of these diseases. Increasing ammonia signals end-stage liver disease and a high risk of hepatic coma (10-70 µg/dl). Drugs that may cause increased levels of ammonia are: Alcohol Barbiturates Narcotics Diuretics  Liver Function Tests 5’Nucleotidase (5’NTD): is specific for cholestasis or damage to the intra or extrahepatic biliary system Serum Glucose Cholesterol Serological Tests: to demonstrate antibodies DNA tests: hepatitis and other viruses Tests for antimitochondrial antibodies Test for transthyretin (prealbumin)  Liver Function Tests Protein Electrophoresis Bile Acids Alpha-fetoprotein Carcinoembryonic antigen Total protein Fibrinogen  Liver Function Tests Serum Protein Electrophoresis: – Abnormal in both necrotic and obstructive liver diseases – In the acute stages of hepatitis, the albumin will be low and the gamma globulin fraction will be elevated. The alpha-1 globulin and alpha-2 globulin fractions will be elevated – In biliary cirrhosis the beta globulin may be elevated owing to an increase in beta lipoprotein – In hepatic cirrhosis the albumin will be greatly decreased  Liver Function Tests Liver function tests performed individually do not give the physician very much information, but used in combination with a careful history, physical examination and imaging studies, they contribute to making an accurate diagnosis of the specific liver disorder Differentiation of acute and chronic forms of hepatocellular injury is aided by examining the ratio of ALT to AST, called the DeRitis ratio. In acute hepatitis, Reye’s syndrome and infectious mononucleosis the ALT predominates. However, in alcoholic liver disease, chronic hepatitis and cirrhosis, the AST predominates  Liver Function Tests ALT values are significantly increased in cases of hepatitis and moderately increased in cirrhosis, liver tumors, obstructive jaundice AST values are increased in liver damage, hepatitis ALP values are increased in diseases that impair bile formation (cholestasis) GGT values are elevated in hepatitis, cirrhosis, liver tumors or metastasis, toxic injury to the liver mainly by alcohol LDH levels are elevated in viral hepatitis Bilirubin levels: increased indirect or total bilirubin levels in hemolytic disease and transfusion reaction. Increased direct bilirubin levels can be diagnostic of bile duct obstruction, gallstones, cirrhosis, or hepatitis  Liver Function Tests The most prevalent liver disease is viral hepatitis. Tests for this condition include a variety of antigen and antibody markers and nucleic acid tests. Acute viral hepatitis – is associated initially with 20 to 100 fold increases in transaminases and is followed shortly by bilirubin elevation. – Such patients should be tested for hepatitis B surface antigen (HbsAg) and IgM antibodies to hepatitis B core antigen (anti-HBc IgM) and anti-hepatitis C virus (anti-HVC) to identify these causes. – In addition to hepatitis A-E, viral hepatitis may be caused by Epstein- Barr virus (EBV) and cytomegalovirus (CMV) infections of the liver. – Tests for these viruses such as the infectious mononucleosis antibody test, anti-viral capsid antigen test (anti-VCA), and anti-CMV tests are useful in diagnosing these infection  Risk factor of chronic viral hepatitis injection drug use birth to mother with HBV blood transfusion prior to 1992 needle stick from a donor subsequently testing positive for HBV or HCV chronic hemodialysis unvaccinated health care workers homosexual body piercing or tattooing  Liver Function Test normal may have abnormal test normal value not ensure that patient is free of liver disease level of abnormality does not reflect severity but may help in DDx decrease in the value does not mean improvement limitation in sensitivity and specificity