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

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

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. Disease Progression 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

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

8. 24♀ 48hours post POD ALT 13000 Alb 35 Bili 40 Cr 160 Urea 24 INR 3.0 PT 33 Glc 3.6 Ph 7.1 PCO 2 3.2 PO 2 12.4 BE -6

9. ALF Treat the underlying cause Resuscitate - Central access early Give N-Ac regardless of cause Monitor for hypoglycaemia Monitor coagulopathy Antibiotic prophylaxis Stress Ulcers Early elective ventilation for encephalopathy Nutrition Acidosis/ Renal Impairment Early referral to Hepatology / discuss with Birmingham Liver Unit

10. 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

11. OE Jaundice Drowsy Agitated/Irritable Doesn’t obey commands No stigmata of CLD Asterixis No spleen No ascites

12. Mrs W U&Enormal ALP107 ALT736 Bili 363 Alb 24 FBC Normal INR3.7

13. Causes of Acute Liver Failure 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

14. 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

15. Cirrhosis Expanded Portal Tracts (Blue)

16. 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

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

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

19. 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)

20. 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 Low urinary Na Dilutional hyponatraemia Ascites Schrier et al Hepatol 1988 Plasma volume expansion NaCl Ascites and Oedema

21. General Management Ascites and Oedema Salt restriction Diuretics spironolactone frusemide Water restriction if sodium < 125 mmol Paracentesis diagnostic (SBP, tumour) therapeutic (20% Alb) DAILY WEIGHTS!

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

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

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

25. 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

26. General Management Encephalopathy Minimize effects of liver disease Treat precipitants sepsis GI bleed medications (over-diuresis) Avoid sedatives, hypnotics, opiates Lactulose to ensure BO 2x/day Metronidazole/ neomycin

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

29. Portal Circulation

30. Oesophageal varices

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

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

33. Fluid Management Crystalloid Colloid Blood Platelets FFP Vitamin K

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

35. Oesophageal varices

36. Bleeding Gastric Varices

37. Variceal Bander

38. Variceal Band Ligation

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

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

41. Sengstaken-Blakemore Tube

42. Complication of SBT

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

45. 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!