Liver disease and how to manage it!

1. Liver disease and how to manage it! Dr Allister J Grant Consultant Hepatologist Leicester Liver Unit University Hospitals Leicester NHS Trust

2. IVC Portal Vein Hepatic Artery Splenic Vein CBD Gallbladder SMV Anatomy &Physiology

3. Anatomy &Physiology

4. Liver Functions Nutrition/Metabolic – stores glycogen (glucose chains) – releases glucose – absorbs fats, fat soluble vitamins – manufactures cholesterol Bile Salts – lipids derived from cholesterol – dissolves dietary fats (detergent) Bilirubin – breakdown product of haemoglobin

5. Liver Functions Clotting Factors – manufactures most clotting factors Immune function – Kupfer cells engulf antigens (bacteria) Detoxification – drug excretion (sometimes activation) – alcohol breakdown Manufactures Proteins – albumin – binding proteins

6. Liver Function Tests Different cells have different enzymes inside them, depending on the function of the cell. AST and ALT are associated with hepatocyte damage GGT and ALP are associated with cholangiocyte damage ie biliary disease

7. Aminotransferases   1. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) These are enzymes that help to process proteins. ALT is more specific for liver disease than AST as AST is found in more types of cell (e.g. heart, intestine, muscle).

8. Alkaline Phosphatase   This enzyme level is elevated in a large number of disorders that affect the drainage of bile e.g. • Gallstones damaging the bile duct • Tumor blocking the common bile duct • Drug-induced cholestatic hepatitis, blocking the flow of bile in smaller bile channels within the liver The alkaline phosphatase is also released from damaged • bone, • placenta, and • intestine (isoenzymes) For this reason, the GGT is utilized as a supplementary test to be sure that the elevation of alkaline phosphatase is indeed coming from the liver or the biliary tract

10. Other Liver “Enzymes” 3) Albumin is a major protein which is produced by the liver In more advanced liver disease, the level of the serum albumin is reduced. 4) Bilirubin is the main bile pigment in humans. Bilirubin is formed primarily from the breakdown of called "haem” from red blood cells When elevated, bilirubin causes the yellow discoloration of the skin and eyes- jaundice and maybe associated with dark urine. The bilirubin may be elevated in many forms of liver or biliary tract disease, and thus it is also relatively nonspecific.

11. Other Liver Enzymes 5) Gamma Glutamyl Transpeptidase is often elevated in liver disorders but not in diseases of bone, placenta, or intestine.  However the high sensitivity and very low specificity of this test seriously hampers its usefulness. GGT is elevated in a whole host of liver diseases BUT also in • obesity • hyperlipidaemia • diabetes • congestive cardiac failure • diseases of the kidney, pancreas and prostate.

12. ALT elevated? (>53) • Hepatitic illness • Acute • Age • Sex • Drugs • Alcohol • Travel • Contacts • Risky behaviour • Autoimmunity • Fever • AF/BP/CCF • Pregnant? • Chronic • Age/sex • Ethnicity • BMI • Lipids • Diabetes • Alcohol • Travel • Risky behaviour • FHx • Autoimmunity • Unexplained Cirrhosis

13. The majority of abnormal LFTs in asymptomatic people occur in those with: • Diabetes or metabolic syndrome (increased risk of NAFLD) • Excessive alcohol intake • Chronic hepatitis B or C • Drugs

15. ALT elevated • Hepatitic illness • Acute • Hep A,B,C,E • EBV, CMV, TOXO • Drugs screen? • Immunoglobulins • Autoimmune profile • Caeruloplasmin (<50) • Chronic • TFT • Diabetic screen • Hep B, C • Lipids • Immunoglobulins • Autoimmune profile • Ferritin • Caeruloplasmin (<50) • α-1 antitrypsin • TTG • (ACE)

16. ALP Elevated? (>130) • Cholestatic Illness (With or without jaundice) • Acute • Age/Sex • Drugs/Antibiotics • FHx gallstones • Abdo Pain • Red flag symptoms • Jaundice? Differentiate from bony • Chronic • Family Hx • Metabolic syndrome • Recurrent Fever • Itch/lethargy • Dry eyes/mouth • Colitis • Pain • SOB/Resp symptoms • CCF

17. Liver ALP Elevated • Cholestatic Illness • Acute • CBD stones/Gallstones • Tumours 1º or 2º • Pancreatic pathology • Drugs • Infiltration • SOD • Chronic • PBC • Sclerosing Cholangitis • 1º or 2º • NASH • α-1 antitrypsin • Sarcoid • Amyloid • HIV

18. Drug Induced Cholestasis • Intrahepatic Hepatocellular Cholestasis • Intrahepatic Ductular cholestasis • Ductopenic • Granulomatous • AllopurinolAntithyroid agents AugmentinAzathioprineBarbituratesCaptoprilCarbamezepineChlorpromazineChlorpropamideClindamycin ClofibrateDiltiazem Erythromycin estolateFlucloxacillin Isoniazid LisinoprilMethyltestosterone Oral contraceptives (containing estrogens)Oral hypoglycemics PhenytoinTrimethoprim-sulfamethoxazole

19. Investigation of Cholestasis Raised ALP Check GT if isolated rise Consider MRCP ERCP Other imaging Dilated bile ducts 1) Stop alcohol 2) Stop hepatotoxic drugs 3) Advise weight loss if BMI>25 4) Recheck LFT’s after an interval Non-dilated bile ducts Diagnosis made- Treat disease Non diagnostic Ix- consider Liver biopsy Full liver screen Persistently raised ALP

20. Isolated raise in Bilirubin (>22) • Differential Gilberts vs Haemolysis • Gilberts- Unconjugatedhyperbilirubinaemia • Haemolysis- Unconjugated hyperbilirubinaemia splenomegaly, anaemia , DCT, haptoglobin, reticulocyte count, film

21. Disease Progression 100% A B Liver function Cirrhosis Liver Failure C D Years

22. Mrs W • 48 year old ♀ admitted from a surgical clinic with jaundice and unwell • Unwell for 6 wks after holiday in Mexico • Hx of xs alcohol 30u/wk • No previous jaundice • USS normal size liver and spleen – biliary tree normal

23. Jaundice Drowsy Agitated/Irritable Doesn’t obey commands No stigmata of CLD Asterixis (Liver Flap) OE No spleen No ascites

24. U&E normal ALP 107 ALT 736 Bili 363 Alb 24 FBC Normal INR 3.7 Mrs W

25. Drugs Paracetamol (UK) INH Halothane Ecstacy Viral Hepatitis A Hepatitis B Hepatitis E Non-A Non-B Wilsons Disease Autoimmune Hepatitis Reye’s Syndrome Cardiovascular Ischaemic hepatitis Budd Chiari Acute Fatty Liver of Pregnancy Causes of Acute Liver Failure

26. Cirrhosis Expanded Portal Tracts (Blue)

27. Signs of Chronic Liver Disease • None • Asterixis/Flap • Relative hypotension • Oedema • Jaundice/No jaundice • Large/Small liver • Splenomegaly • Gynecomastia • Testicular atrophy-loss of secondary sexual characteristics • Impotence

28. Decompensation in Cirrhosis Means the development of- Ascites Hepatic Encephalopathy Portal hypertension (variceal haemorrhage)

29. The Development of Ascites 50% of compensated cirrhotics develop ascites over 10yrs 50% of cirrhotics with ascites will die within 2 yrs

30. Encephalopathy • Grade 1 • Constructional apraxia • Poor memory – number connection test • Agitation/ irritability • Reversed sleep pattern • Grade 2 • Lethargy, disorientation • Asterixis • Grade 3 • Drowsy, reduced conscious level • Grade 4 • Coma

32. Decompensation in Cirrhosis Means the development of- Ascites Hepatic Encephalopathy Portal hypertension (variceal haemorrhage)

33. Portal Circulation

34. Oesophageal varices

35. Management of Bleeding Varices • Prevention • Prophylactic Antibiotics • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS

36. Management of Bleeding Varices • Prevention • Prophylactic Antibiotics • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS

37. Oesophageal varices

38. Bleeding Gastric Varices

39. Variceal Bander

40. Variceal Band Ligation

41. Management of Bleeding Varices • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin 2mg qds i.v • Balloon Tamponade • TIPS

42. Management of Bleeding Varices • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS

43. The END • Allister.J.Grant@uhl-tr.nhs.uk • 0116 258 6630 • http://hepatologist.sharepoint.com