MPharm Programme Liver Biochemistry Slide 1 of 49 MPHM Liver Biochemistry
Learning Outcomes Assess and evaluate the signs and symptoms of illness Assess and critically appraise a patients medication regimen, identify areas in which improvements to care may be made and propose suitable solutions Propose solutions and plans in relation to the management of a clinical condition Slide 2 of 49 MPHM Liver Biochemistry
Aims Understand the role and function of the liver Know the signs and symptoms of liver disease Know the common liver function tests (LFTs) and their significance What deranged LFTs and liver disease mean to the pharmacy team Know the complications associated with liver disease Know the reference sources available Slide 3 of 49 MPHM Liver Biochemistry
Introduction Liver disease is a growing epidemic in the UK 5 th big killer in England and Wales after heart disease, cancer, stroke and respiratory disease Only major cause of death increasing year on year Mainly due to lifestyle issues Slide 4 of 49 MPHM Liver Biochemistry
Introduction Largest solid organ in the human body 2-3% of adult body mass Located under the diaphragm in the RUQ Slide 5 of 49 MPHM Liver Biochemistry
Introduction As pharmacists: Medicines expertise to improve patient care Optimise therapy Management of problems Patient education Slide 6 of 49 MPHM Liver Biochemistry
Structure of the Liver 2 lobes Highly vascular structure Made up of about 300 billion cells Approximately 80% of these are hepatocytes Slide 7 of 49 MPHM Liver Biochemistry
Structure of the Liver Slide 8 of 49 MPHM Liver Biochemistry
Structure of the Liver Slide 9 of 49 MPHM Liver Biochemistry
Functions of the Liver Homeostasis Immunological Metabolism Synthesis Storage Production of bile Slide 10 of 49 MPHM Liver Biochemistry
Functions of the Liver Homeostasis Glucose Metabolism Carbohydrates Protein Fats Steroid hormones Insulin Bilirubin Drugs Toxins Synthesis Protein Clotting factors Cholesterol Immunological Mobilise the macrophage system Kupffer Cells Slide 11 of 49 MPHM Liver Biochemistry
Functions of the Liver Storage Fat soluble vitamins Glycogen Production of bile Secretion of bile salts Slide 12 of 49 MPHM Liver Biochemistry
Liver Disease Cholestatic Hepatocellular disease Steatosis Hepatitis Fibrosis Cirrhosis Slide 13 of 49 MPHM Liver Biochemistry
Liver Disease Acute Mild Self-limiting Develop into chronic disease Chronic Structural changes Compromise liver function Slide of 49 MPHM Liver Biochemistry
Symptoms Initially: Non-specific Easily fatigued Nausea Often: Loss of appetite Weight loss Slide 15 of 49 MPHM Liver Biochemistry
Symptoms Apparent in decompensated liver disease Loss of muscle from arms and legs Swelling of the abdomen and lower body Abdominal pain Pruritus Bruising Bleeding gums, nose Slide 16 of 49 MPHM Liver Biochemistry
Signs Related to liver being unable to carry out its normal function Reflect the varied role the liver performs Signs of Liver Disease Jaundice Splenomegaly Pigmented ulceration of the skin Fever Purpura Dilated abdominal blood vessels Dupuytren s contracture Gynacomastia Varices Palmar erythema Ascites Neurological changes Finger clubbing Bruising and bleeding Slide 17 of 49 MPHM Liver Biochemistry Hepatic flap Spider naevi Altered liver mass Xanthelasmas White nails Oedema
Signs Spider Navei Dupuytren s contracture Ascites Palmar Erythema Slide 18 of 49 MPHM Liver Biochemistry
Causes Causes Alcohol Examples Alcoholic liver disease Viral Infections Hepatitis (A, B, C, D, E) Fatty liver Malignancy Immune disease Inherited and metabolic disorders Drugs and toxins NASH, NAFLD HCC Autoimmune hepatitis Alpha1-antitrypsin deficiency, Wilson s disease Paracetamol, phenytoin, oral contraceptives, methotrexate Slide 19 of 49 MPHM Liver Biochemistry
Liver Function Tests No single marker of liver dysfunction Use a combination of factors: LFTs and additional tests Diagnosis Signs and symptoms Slide 20 of 49 MPHM Liver Biochemistry
Liver Function Tests Standard LFTs Albumin ALT AST GGT ALP Bilirubin Also need to remember: Clotting screen Slide 21 of 49 MPHM Liver Biochemistry
Liver Function Tests: Albumin Albumin (34 45 g/l) Manufactured in the liver Half life: 20 days Acute liver disease: normal Useful guide to the severity of chronic liver disease Consider extrahepatic causes for low levels Slide 22 of 49 MPHM Liver Biochemistry
Liver Function Tests: ALT Alanine transferase (0 40 IU/L) Released from hepatocytes when they are damaged Cytosol enzyme More specific to the liver than AST May also indicate a drug-induced reaction Slide 23 of 49 MPHM Liver Biochemistry
Liver Function Tests: AST Aspartate transferase (0 40 IU/L) Released from hepatocytes when they are damaged Primarily found in mitochondria Also present in the heart, pancreas, kidney, lung, muscle and red blood cells AST and ALT tend to rise and fall at the same time May indicate a possible drug-induced reaction Slide 24 of 49 MPHM Liver Biochemistry
Liver Function Tests: AST:ALT Ratio of AST:ALT may help in making a diagnosis more or less likely Hepatocellular injury AST lower than ALT Chronic liver disease Established cirrhosis (AST >ALT) AST:ALT of 2:1 or greater Alcoholic Liver Disease Especially if rise in GGT Slide 25 of 49 MPHM Liver Biochemistry
Liver Function Tests: GGT Gamma-Glutamyl transpeptidase (0 50 IU/L) Enzyme Hepatocytes, biliary epithelial cells, kidney, pancreas, intestine, prostate Released in all types of liver dysfunction Indicate alcohol abuse If taking enzyme inducing drugs Slide 26 of 49 MPHM Liver Biochemistry
Liver Function Tests: ALP Alkaline phosphatase (30 120 IU/L) Check your local range Isoenzyme Produced in hepatocytes Raised in cholestatic disease Isolated rise may not be associated with liver dysfunction Slide 27 of 49 MPHM Liver Biochemistry
Liver Function Tests: Bilirubin Bilirubin (5-21µmol/L) Breakdown product of RBC Transported to the liver, attached to albumin In the liver bilirubin is conjugated Excreted via the bile Levels rise: When damage to the liver occurs, resulting in jaundice Biliary tract obstruction Haemolysis Slide 28 of 49 MPHM Liver Biochemistry
Clotting Factors Prothrombin Produced in the liver Vitamin K dependent Prothrombin Time (12 16 seconds) Marker of synthetic function Time taken for a clot to form Exclude vitamin K deficiency Slide 29 of 49 MPHM Liver Biochemistry
Liver Function Tests Need to consider all components of LFTs Consider them together Look at over a period of time Trends Slide 30 of 49 MPHM Liver Biochemistry
Liver Function Tests ALT/AST ALP Bilirubin Albumin PT Cholestasis 3 10xULN 3 10xULN Hepatitis 20xULN to 3xULN 2 10xULN to 75% of normal to 2xULN Acute >20xULN to 3xULN Compensated to 3xULN to 2xULN to 10xULN 10xULN to 20xULN to 75% of normal Decompensated to 3xULN to 3xULN to 20xULN to 50% of normal 2xULN Slide 31 of 49 MPHM Liver Biochemistry
Liver Function Additional tests: Ultrasound Doppler Biopsy Computed Tomography (CT) ERCP MRI Tools to grade severity: Child-Pugh classification Slide 32 of 49 MPHM Liver Biochemistry
Complications Portal hypertension Ascites Encephalopathy Bleeding varices Spontaneous bacterial peritonitis (SBP) Pruritus Deranged clotting Hepatorenal syndrome (HRS) Slide 33 of 49 MPHM Liver Biochemistry
Portal Hypertension Increased pressure in portal venous system Collateral veins develop Contribute to ascites and encephalopathy Treatment: Propranolol Slide 34 of 49 MPHM Liver Biochemistry
Ascites Swollen abdomen Accumulation of fluid Reduction in serum albumin Portal hypertension Decrease in aldosterone metabolism Treatment: Mobilise excess fluid Diuretics Paracentesis Slide 35 of 49 MPHM Liver Biochemistry
Encephalopathy Cause is unclear: occurs with significant liver dysfunction Altered permeability of the BBB Ammonia Altered mental state, asterixis Treatment: Aim is to reduce ammonia in circulatory system Lactulose Antibiotics Rifaximin Slide 36 of 49 MPHM Liver Biochemistry
Bleeding varices Upper GI bleeding Aim: stop or slow down blood loss, treat hypovolaemic shock, prevent recurrent bleeding Treatment Terlipressin Balloon tamponade Slide 37 of 49 MPHM Liver Biochemistry
Spontaneous bacterial peritonitis Well known complication of cirrhosis Acute bacterial infection of ascitic fluid Mortality rate: 40 70% Treatment: Acute IV antibiotics Prophylaxis High risk patients Quinolones Slide 38 of 49 MPHM Liver Biochemistry
Pruritus Common and distressing Deposition of bile salts within the skin Treatment: Depends on severity Antihistamines Ursodeoxycholic acid Anion exchange resins Slide 39 of 49 MPHM Liver Biochemistry
What does this mean for the Pharmacy Team? Key area for pharmacy intervention Recommendations of medicine use Consider: LFTs Signs and symptoms of liver disease Properties of drugs Pharmacokinetics Pharmacodynamics Side-effect profile of drugs Slide 40 of 49 MPHM Liver Biochemistry
Considerations Pharmacokinetics Altered kinetics in patients with liver disease Absorption Distribution Metabolism Elimination Unpredictable Depend on the type of liver disease Slide 41 of 49 MPHM Liver Biochemistry
Considerations Pharmacokinetics Hepatic blood flow Reduced Increase in systemic bioavailability of oral drugs undergoing 1 st pass metabolism Portosystemic shunting 60% of blood supply diverted Slide 42 of 49 MPHM Liver Biochemistry
Considerations Reduced hepatic cell mass Severe disease: 30% capacity Consider drugs extensively metabolised by the liver Reduction in protein binding Lower serum albumin Highly protein drugs Drug free concentration will increase Slide 43 of 49 MPHM Liver Biochemistry
Considerations Pharmacodynamics Side-effects Exacerbation of complications Examples: Opioids Benzodiazepines Diuretics NSAIDs Slide 44 of 49 MPHM Liver Biochemistry
Drug-Induced Liver Disease Be aware of potential adverse drug reactions as a cause of liver disease Implicated drugs: Statins NSAIDs Penicillin's Can present weeks or months after the medication has been started or even stopped Slide 45 of 49 MPHM Liver Biochemistry
Case Study 41 year old male presents to A&E PMH: chronic alcoholic LFTs: Test Bilirubin (5-21) Result 35 (5-21µmol/L) AST ALT ALP GGT Albumin PT 62 (0 40 IU/L) 21 (0 40 IU/L) 112 (30-120 IU/L) 97 (0 50 IU/L) 20 (34 45g/L) 32 (12 16 seconds) Slide 46 of 49 MPHM Liver Biochemistry
Case Study AST:ALT is 3:1 GGT is raised Alcoholic liver disease Liver enzymes are not elevated much Cirrhosis Slide 47 of 49 MPHM Liver Biochemistry
You should Understand the structure and function of the liver Know the basic liver function tests Understand how to interpret the test results What the results indicate Recognise signs and symptoms of liver disease Drugs involved in liver injury Slide 48 of 49 MPHM Liver Biochemistry
References British Liver Trust: http://www.britishlivertrust.org.uk Drugs and the Liver (2008), Ed. P. North- Lewis, Pharmaceutical Press, London The United Kingdom Medicines Information Centre: http://www.ukmi.nhs.uk BNF Electronic Medicines Compendium Slide 49 of 49 MPHM Liver Biochemistry