Dr Allister J Grant Consultant Hepatologist University Hospitals Leicester NHS Trust

1. Dr Allister J Grant Consultant Hepatologist University Hospitals Leicester NHS Trust

2. Anatomy &Physiology

3. Anatomy &Physiology

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

5. Anatomy &Physiology

6. Liver Functions Nutrition/Metabolic – stores glycogen (glucose chains) – releases glucose when if no insulin – absorbs fats, fat soluble vitamins – manufactures cholesterol Bile Salts – lipids derived from cholesterol – dissolves dietary fats (detergent) Bilirubin – breakdown product of haemoglobin

7. 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

8. Early disease asymptomatic fatigue, malaise anorexia, nausea jaundice pruritis easy bruising and bleeding abdominal pain Cholestatic patients fatigue, malaise anorexia, nausea jaundice +++ pruritis +++ grey or clay-coloured stools Symptoms

9. Acute Liver Failure <6 weeks duration Jaundice Encephalopathy Cerebral Oedema Acute Renal Failure Acidosis Hypoglycaemia MOF Chronic Liver Disease >6 months Cirrhosis leading to Recurrent decompensation Ascites Portal Hypertension (variceal bleeding) Encephalopathy Low albumin/Malnutrition Hepatorenal syndrome Hyponatraemia Hepatoma Disease Progression

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

11. Viral Hepatitis B Hepatitis C Autoimmune Hepatitis Metabolic NASH Amyloid Alcoholic Cirrhosis Inherited Haemochromatosis Wilsons Disease -1 Antitrypsin Deficiency Biliary Disease PBC PSC Secondary sclerosing cholangitis Caroli’s syndrome Causes of Chronic Liver disease

12. 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

13. Cirrhosis Expanded Portal Tracts (Blue)

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

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

16. The Development of Ascites 50% of compensated cirrhotics develop ascites over 10yrs 50% of cirrhotics with ascites will die within 2 yrs (50% 2yr rule for OLTx assessment)

17. NaCl The Development of Ascites Peripheral arterial dilatation Reduced effective blood volume Activation of renin-angiotensin-aldosterone system Sympathetic nervous system ADH Na retention & Water retention Ascites and Oedema Low urinary Na Dilutional hyponatraemia Plasma volume expansion Ascites Schrier et al Hepatol 1988

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

19. 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

20. Causes of Encephalopathy INCREASED AMMONIAGENESIS Increased substrate (protein) for ammoniagenesis • Increased protein intake • Gastrointestinal bleeding • Constipation • Dehydration Increased substrate (urea) for ammoniagenesis • Renal failure Increasedcatabolism of protein • Infection • Hypokalemia • Sepsis

21. Causes of Encephalopathy DECREASED HEPATOCELLULAR FUNCTION • Worsened intrinsic liver disease • Hypoxia • Anaemia • Development of hepatocellular carcinoma • Dehydration • Hypotension • Sepsis • Drug toxicity • Superimposed viral hepatitis

22. INCREASED PORTOCAVAL SHUNTING Portal vein thrombosis Transjugular intrahepatic portosystemic shunt formation Surgical shunt formation Spontaneous shunt formation PSYCHOACTIVE DRUG USE Benzodiazepines Ethanol Antiemetics Antihistamines Others Causes of Encephalopathy

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

25. Portal Circulation

26. Oesophageal varices

27. Prognosis 1 Year Survival – Child Pugh A 80 - 100% – Child Pugh B 60 - 80% – Child Pugh C 35 - 45%

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

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

30. Fluid Management • Crystalloid • Colloid • Blood • Platelets • FFP • Vitamin K

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

32. Oesophageal varices

33. Oesophageal varices

34. Bleeding Gastric Varices

35. Variceal Bander

36. Variceal Band Ligation

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

38. PharmacotherapyTerlipressin vs. Balloon TamponadeMortality Favours Terlipressin Favours Tamponade Terlipressin vs. Endoscopic TherapyMortality

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

40. Sengstaken-Blakemore Tube

41. Complication of SBT

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

44. The End “All right, let's not panic. I'll make the money by selling one of my livers. I can get by with one “ Doh!