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Chronic Liver Disease

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Title: 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 (lt1week)
  • Acute liver failure (7-28 days)
  • Fulminant liver failure
  • (1 month-6 months)
  • Chronic (gt6 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
  • a1- antitrypsin deficiency (early severe
    fibrosis)
  • Primary biliary cirrhosis (AMA, young women
    autoimmune)
  • Primary sclerosing choloangitis (ANA,
  • Haemochromatosis early onset jaundice, bronze
    diabetes
  • Wilsons 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, Wilsons, 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 B Hepatitis C
Virus DNA RNA
Spread Blood, sexual Blood
Presentation Fever, malaise, anorexia, nausea, arthralgia, jaundice, RUQ pain Usually asymptomatic early on
Investigation See below. Biopsy Anti-HCV, HCV DNA. Biopsy.
Chronic 5-10 85
Treatment Supportive. 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
  • 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)
  • UEs (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
  • 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
  • Wilsonss - penicillamine
  • Hepatic encephlopathy laxatives, antibiotics,
    IV fluids (avoid NaCl), mannitol
  • SBP antibiotics e.g. tazocin
  • Surgical
  • TIPSS
  • Peritoneal lavage/ascitic tap

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?
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