chronic liver disease

2. Plan
• Introduction to the liver
• Definition
• 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. 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

12. 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)

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

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

15. Signs

16. 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

17. 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

18. 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

19. 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

20. 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

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

22. 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

23. Diabetes
 Poor glucose storage
 Bronze diabetes
 Diabetic therapy
 Dietary modification

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

25. 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

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

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

28. 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

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

30. 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)

31. 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)

32. 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

33. 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

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

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

36. Prognosis

37. 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

38. Management of chronic liver
disease complications
- Spontaneous Bacterial
Peritonitis (SBP)

39.  Fever and chills occur in as many as 80% of
patients. Abdominal pain or discomfort is found in as
many as 70% of patients.
 Other signs and symptoms may include the
following:
• Worsening or unexplained encephalopathy
• Diarrhea
• Ascites that does not improve following
administration of diuretic medication
• Worsening or new-onset renal failure
Presenting History

40. Physical Examination
 Abdominal tenderness is found in more than 50% of
patients with spontaneous bacterial peritonitis.
Findings can range from mild tenderness to overt
rebound and guarding.
 In some cases, the abdominal examination findings
mimic an acute intra-abdominal catastrophe
requiring emergency surgical evaluation. Physical
examination may also disclose hypotension (5-14%
of patients) or signs of hepatic failure such as
jaundice and angiomata.

41. Investigation
 Diagnostic paracentesis (occurring within the first 11
hours of presentation)
 Biomarker for SBP (in patients with cirrhosis) is
Calprotectin, a diagnostic marker of inflammation.
 it is a calcium and zinc-binding protein that is found
exclusively in neutrophils.
 high calprotectin level indicates an inflammatory or
infectious process

42.  Blood and urine cultures (guide antibiotic therapy)
 If there is clinical suspicion of a perforated viscus,
imaging should be strongly considered.
 Plain radiographs (including abdominal flat plate,
abdominal upright, and chest)
 CT scanning of the abdomen should be considered,
as it is much more sensitive for a small perforation.

43. Peritoneal Tapping Test
(Diagnostic Test)

44. SAAG calculation