1. Tim Badcock FY1 Colorectal surgery 21/10/13

2. Plan Introduction to the liver Definition Clinical Scenario Presentation Aetiology Complications Investigations Management Prognosis

3. Introduction to the liver 5 Functional domains 4 lobes 3 vascular 2 important ligaments 1 Biliary tree

4. 5.Domains Synthetic – Albumin – Clotting factors (1972) Metabolism – CYP350 drugs – Gluconeogenesis/glycogenesis/glycogenolysis – Homeostasis – Iron, copper, vitamin K Vascular Immunological – Kuppfer cells beside sinusoids Biliary tree – Bilirubin – Left/right hepatic = common hepatic duct – Common hepatic + bile duct = common bile duct – Common bile duct + pancreatic duct

5. 4. Lobes Left Right Caudate Quadrate

6. 3. Vascular structures Hepatic portal vein (80%) Hepatic artery (18%) Hepatic vein (2%)

7. 2. Ligaments Falciform (developmental structure of liver, umbilical vein) Venosum (ductus venosus)

8. 1. Biliary tree 1 8 7 5 6 9 3 4 2

9. Definition Acute/chronic, organ system, key characteristics A chronic reduction in hepatic function characterised by poor synthetic, metabolic, and immunological functions and vascular compromise associated with ascites and portal hypertension. Also associated with acute decompensation events characterised by acute haemorrhage, severe abdominal infection, neurological impairment and oedema

10. Timing Hyperacute (<1week) Acute liver failure (7-28 days) Fulminant liver failure (1 month-6 months) Chronic (>6 months)

11. Clinical scenario 54 year old gentleman presents to his GP with increasing swelling of his abdomen and feet over the last 2 months. He has been increasing tired over this time and feels nauseous and is off his food. His wife has commented that his eye have turned yellow over the last few days. He works in a warehouse and smokes 10 cigarettes a day. He admits to drinking 4 cans of lager a night. His wife says he drinks at least 8 cans a night and a bottle of whiskey a week. He noticed that he bled profusely when he cuaght himself on a baked beans can

12. Case study On examination he has pale white nails and a slghtly bent 4 th finger. He has man boobs. He is jaundiced but has no hepatic flap and is orientated in time, place and person. His abdomen is distended but soft and non- tender. There is no palpable organomegaly but there is shifting dullness. A raised JVP is noted on hepatic compression

13. Presentation Synthetic – Albumin – ascites, infection – Clotting - variceal bleed, haematemesis, meleana Metabolism Bilirubin – jaundice CYP450 drugs – variable INR, toxicity ODEVICES = inhibitor PCBRAS – inducer Hepatic encephalopathy Hypoglycaemic Hormones – high oestrogen Syndromes

14. Autoantibodies against hepatocytes. Often young women with other autoimmune conditions. RUQ pain and jaundice α1- antitrypsin deficiency (early severe fibrosis) Primary biliary cirrhosis (AMA, young women autoimmune) Primary sclerosing choloangitis (ANA, Haemochromatosis – early onset jaundice, bronze diabetes Wilson’s disease – Keyser-Flescher, serum caeruloplasmin Gilbert Syndrome (UDP glucoronyl transferase, early mild jaundice) Crigler Nijjar syndrome (severe early, kernicterus)

15. Presentation Vascular Hepatomegaly (RUQ pain) Splenomegaly Haematesis (oesophageal varices) Meleana Immunological Spontaneous bacterial peritonitis

16. Biliary tree Jaundice Pre-hepatic (dark stools) Hepatic (dark urine, normal/pale stools) Obstructive (dark urine, pale stools) Urobilinogen/ stercobilinogen

17. Signs

18. Aetiology Alcoholic liver disease Non-alcoholic fatty liver disease Viral liver disease Primiary biliary sclerosis, Primary sclerosing cholangitis, Wilson’s, HH etc Hepatocellular Carcinoma (rare, UC) Metastasis (common)/ Pancreatic cancer (rare) Cryptogenic Liver Cirrhosis

19. Pathophysiology Chronic inflammatory (swelling, fatty infiltraton, cytoplasm granulation) Eosinophil and macrophage invasion Lytic necrosis Fibrosis and contracture Loss of liver architecture Sinusoids Acinii Portal triad

20. Alcoholic fatty liver disease High calorie intake in alcohol Fat droplets deposit in hepatocytes Ethanol directly affects cell membrane stability as does aldehyde Chronic necrosis of cells with fibrosis Later becomes small cirrhotic liver

21. Non-alcoholic fatty liver disease 5% population, asymptomatic Seen on US abdo/biopsy Diabetes Mellitus Metabolic syndrome (HTN, hypercholesteraemia, diabetes) Pregnancy (high oestrogen) Idiopathic Oxidative stress and steatohepatitis

22. Hepatitis B & C Hepatitis BHepatitis C VirusDNARNA SpreadBlood, sexualBlood PresentationFever, malaise, anorexia, nausea, arthralgia, jaundice, RUQ pain Usually asymptomatic early on InvestigationSee below. BiopsyAnti-HCV, HCV DNA. Biopsy. % Chronic5-10%85% TreatmentSupportive. Chronic: antivirals (nucleoside analogues). Transplant Nucleoside analogues, protease inhibitors (anti-retroviral). Liver transplant HbcAg = core antigen = replicating HBeAg = pre-core antigen = current infection HBsAg = surface antigen = acute/chronic HBV DNA = infectious Anti-HBc = active infection Anti-HBe = latent infection if HBeAg +ve vaccinated if HBeAg -ve

23. Complications Portal hypertension Diabetes Spontaneous bacterial peritoneal Hepatic encephalopathy Liver transplant Malnutrition Renal failure

24. Portal hypertension Oesophageal varices (azygous veins) Rectal varices (inferior rectal veins) Caput medusae (umbilical veins) Budd-Chiari syndrome (hepatic vein thrombosis) TIPSS (transjugular intrahepatic portosystemic shunt) OGD +/- Variceal banding, stent, sclerotherapy Massive haemorrhage protocol

25. Diabetes Poor glucose storage Bronze diabetes Diabetic therapy Dietary modification

26. Spontaneous bacterial peritoneal 8% ascites Severe abdominal pain Severely unwell Ascitic tap Peritoneal lavage Intravenous antibiotics Liver transplant

27. Hepatic encephalopathy Increased ammonia from bacterial activity on protein in faeces Liver bypass (TIPSS) Haemorrhage Foetor hepaticus Hepatic flap (asterix) Decreased mental capacity e.g. Constructional apraxia West Haven Criteria Grade I altered mood/behaviour Grade II reduced consciousness Grade III Stupor Grade IV Coma Enemas, lactulose, niacin, IV fluids

28. Liver transplant End stage liver failure SBP Congenital syndromes Strict criteria for transplant Long term immunosuppresants (azathioprine, ciclosporin) Avoid alcohol

29. Malnutrition Encourage highest possible protein intake High calorie intake Avoid alcohol Chlordiazepoxide Acamprosate Disulfiram

30. Renal failure Increased vascular pressure from portal hypertension into splenic and renal veins Diabetic nephrotic syndrome – minimal change Hepatorenal syndrome – low oncotic pressure triggers peripheral hypovolaemia, neuropepetide Y and RAAS activation leads to constriction of afferent and dilatation of efferent arterioles leading to renal hypoperfusion

31. Investigations Biological Bedside Bloods Imaging Special Psychological Alcohol addiction Depression Social Unemployment Supportive housing

32. Biological Bedside Observations (BP, pyrexia, BM) ECG ABG GCS/West Haven Bloods FBC (anaemia, WCC) U&Es (urea, creatinine) LFTs (all important) Clotting (intrinsic and extrinsic) CRP (infective) Cholesterol (fatty) HbA1c Gamma GT (alcohol) Antibodies Imaging US Abdomen CT abdomen CT angiography CXR ERCP Special Drugs e.g. paracetemol OGD (varices) Hepatitis screen/leptospirosis Ascitic tap Liver biopsy (cancer, severity) PET scan (mets) Colnoscopy (ulcerative colitis)

33. Liver function tests Total protein = albumin + globins Albumin – long term synthetic Bilirubin – bile production/retention, Gilberts/Crigler Nijjar, Sickle cell, Iatrogenic - carbimazole ALP – bile duct inflammation + bone + hyperoestrogenic states, drugs ALT – hepatocyte inflammaion + thyroid dysregulation + coeliac + exercise Clotting – INR, APTT Extras – amylase, gGT, paracetemol (NAC)

34. Acute Management Personal Alcohol abstinence Fluid restriction 10% dextrose infusion/sliding scale Raise head of bed Medical Jaundice – urseodoexycholic acid, colystyramine reduces pruritus Alcohol complications - Pabrinex (IV/PO), chlordiazepoxide Ascites – Diuretics, Paracentesis, NG feeding Ulceration – omeprazole Bleeding – vitamin K/octaplex Wilsons’s - penicillamine Hepatic encephlopathy – laxatives, antibiotics, IV fluids (avoid NaCl), mannitol SBP – antibiotics e.g. tazocin Surgical TIPSS Peritoneal lavage/ascitic tap

35. Chronic management Personal Alcohol abstinence Optimise nutrition Low salt diet Medical Jaundice – urseodoexycholic acid, Ascites – Diuretics Hepatic encephlopathy – laxatives, Autoimmune – steroids Renal failure - Haemodialysis Rastionalise pharmacy Omeprazole Surgical TIPSS Liver transplantation

36. Multidisciplinerary Team GP Psychiatrist Gastroenterology Social services Physiotherapy Dietician Specialist nurses

37. Prognosis 5 year survival rate is 50% Post-transplant 5 year survival 65%

38. Prognosis

39. References Kumar and Clarke, Clinical Medicine Oxford Clinical Handbook of Medicine Washington Hepatitis Study NICE guidelines albumen dialysis NICE guidance living donor liver transplant Review article: the modern management of hepatic encephalopathy by Bhajaj Netters anatomy Child-Pugh scoring article by Child and Pugh BMJ learning – liver disease module Doctors Consultant S Ramcharan, M Osborne, Dr Gelsthorpe Reg. K McArdle, J. Barnes SHO T. Nash

40. THANK YOU Any questions?