Chronic Liver Disease

1. Chronic Liver Disease 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 2 3 4 1 5 6 7 8 9

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 4th 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. Syndromes • 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 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 • 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) • 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

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 • Hepatic encephlopathy – laxatives, antibiotics, IV fluids (avoid NaCl), mannitol • SBP – antibiotics e.g. tazocin Surgical • TIPSS • Peritoneal lavage/ascitictap 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

35. Chronic management Surgical • TIPSS • Liver transplantation 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

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?