Chronic Liver Disease

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Chronic Liver Disease

• Tim Badcock
• FY1 Colorectal surgery
• 21/10/13

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Plan

• Introduction to the liver
• Definition
• Clinical Scenario
• Presentation
• Aetiology
• Complications
• Investigations
• Management
• Prognosis

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Introduction to the liver

• 5 Functional domains
• 4 lobes
• 3 vascular
• 2 important ligaments
• 1 Biliary tree

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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

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4. Lobes

• Left
• Right
• Caudate
• Quadrate

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3. Vascular structures

• Hepatic portal vein (80)
• Hepatic artery (18)
• Hepatic vein (2)

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2. Ligaments

• Falciform (developmental structure of liver,
  umbilical vein)
• Venosum (ductus venosus)

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1. Biliary tree
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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

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Timing

• Hyperacute (lt1week)
• Acute liver failure (7-28 days)
• Fulminant liver failure
• (1 month-6 months)
• Chronic (gt6 months)

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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

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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

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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

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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)

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Presentation

• Vascular
• Hepatomegaly (RUQ pain)
• Splenomegaly
• Haematesis (oesophageal varices)
• Meleana
• Immunological
• Spontaneous bacterial peritonitis

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Biliary tree

• Jaundice
• Pre-hepatic (dark stools)
• Hepatic (dark urine, normal/pale stools)
• Obstructive (dark urine, pale stools)

Urobilinogen/ stercobilinogen
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Signs
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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

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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

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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

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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

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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
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Complications

• Portal hypertension
• Diabetes
• Spontaneous bacterial peritoneal
• Hepatic encephalopathy
• Liver transplant
• Malnutrition
• Renal failure

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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

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Diabetes

• Poor glucose storage
• Bronze diabetes
• Diabetic therapy
• Dietary modification

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Spontaneous bacterial peritoneal

• 8 ascites
• Severe abdominal pain
• Severely unwell
• Ascitic tap
• Peritoneal lavage
• Intravenous antibiotics
• Liver transplant

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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

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Liver transplant

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

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Malnutrition

• Encourage highest possible protein intake
• High calorie intake
• Avoid alcohol
• Chlordiazepoxide
• Acamprosate
• Disulfiram

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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

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Investigations

• Biological
• Bedside
• Bloods
• Imaging
• Special
• Psychological
• Alcohol addiction
• Depression
• Social
• Unemployment
• Supportive housing

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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

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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)

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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

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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

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Multidisciplinerary Team

• GP
• Psychiatrist
• Gastroenterology
• Social services
• Physiotherapy
• Dietician
• Specialist nurses

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Prognosis

• 5 year survival rate is 50
• Post-transplant 5 year survival 65

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Prognosis
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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

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THANK YOU

• Any questions?