1. Dr Kumudith Ekanayaka 15 August 2018
Liver Cases
Dr Kumudith Ekanayaka
15 August 2018

2. Case 1 65 year old female No EtOH BMI 21 Pruritis & fatigue
LFT’s Bil 63 (0-24)
AST 40 (0-45)
ALT 65 (0-55)
GGT 430 (0-60)
ALP 290 (40-110)

3. Case 1 Other Bloods to check? INR 1.8 (<1.2) Alb 32 (35-47)
What other tests?
What is the cause?
What would you do?

4. Case 1 SWE – 15.2 kPa Liver Screen – Negative apart from positive AMA
USS – Mild splenomegaly, coarse echotexture
SWE – 15.2 kPa
Liver Screen – Negative apart from positive AMA
AFP – 4.0 (Normal)
Likely Primary Biliary Cholangitis
Treated with Ursodeoxycholic acid
Cirrhosis followup

5. Case 2 23 year old European female Unwell 2 days
Abdominal pain, Jaundiced and drowsy
Depression otherwise well
OE: Jaundiced, No signs of CLD
LFTs Bil 250
ALP 160
GGT 200
ALT 2380
AST 1960

6. Case 2 Other Bloods: Liver Screen Imaging Pattern of LFT Disturbance
INR 2.3, Cr 85, pH 7.40, Paracetamol 120
Liver Screen
Negative (HAV and HBcoreIgM – Negative)
Imaging
USS: Normal
Pattern of LFT Disturbance
Hyperbilirubinaemia, Hepatitic Picture ALT>1000
Diagnosis
Paracetamol Overdose

7. Case 2

8. Case 2 Liver Transplant Criteria (Kings College) Paracetamol
Arterial pH < 7.3; or
All three: INR>6.5, Cr>300, G3-4 Encephalopathy
Non Paracetamol
INR >6.5; or
Three of the following five criteria
Patient age <11 or >40;
Bilirubin >300;
Time from onset of jaundice to enceph. greater than 7 days;
INR >3.5; or,
Drug toxicity

9. Case 3 Heavy alcohol consumption – Many years Stopped 4 weeks ago
Gradual jaundice, confusion and lethargy
OE: Jaundiced, Spider Naevi, Small liver
LFTs Bil 406
GGT 198
ALP 137
AST 126
ALT 52

10. Case 3 Other Bloods: Liver Screen Imaging Pattern of LFT Disturbance
INR 1.8, Albumin 30
Liver Screen
Negative
Imaging
USS: Coarse Liver Echotexture
Pattern of LFT Disturbance
Mixed, significant hyperbilirubinaemia, AST>ALT
Diagnosis
Alcoholic Hepatitis

11. Case 3

12. Case 3 Treatment Abstinence from Alcohol Monitor for withdrawal
Vitamin K
In Hospital 3 weeks
Good improvement
Prednisone 30mg Daily for 4 weeks
Cirrhosis follow up

13. LFT’s, tests of liver function & Cirrhosis
Dr Kumudith Ekanayaka
15 August 2018

14. Normal Liver Anatomy
Hepatic Artery
Bile Duct
Portal Vein
Central Vein

15. Aetiology of Abnormal LFT’s in my clinic(n= 672)

16. Liver Function Tests (LFT’s)
Routinely ordered
AST not routinely performed by the lab
1-4% of asymptomatic patients have abnormal values
Test results can fluctuate, 30% of abnormal results can normalise (Lazo et al.)
Diagnosis can be reached non invasively

17. LFT’s Liver Enzymes Cholestasis Hepatitis Synthetic Function
ALP (<110 iU/L)
GGT (<60 iU/L)
Hepatitis
ALT (<55 iU/L)
AST (<45 iU/L)
Synthetic Function
Bilirubin (<24 umol/L)
Albumin (35-47 g/L)
Prothrombin Ratio (<1.2)

18. Patterns of raised LFT’s
A purely cholestatic or purely hepatitic picture - uncommon
Cholestatic ALT / ALP < 2
Mixed ALT / ALP
Hepatitic ALT / ALP > 5
[ Ratio = ALT (x ULN) / ALP (x ULN)]

19. Causes of Cholestasis Mechanical Bile duct obstruction Medications
Stones, tumour, surgery, parasites
Medications
Clavulanic acid, Flucloxacillin, Erythromycin
Liver congestion / heart failure
Sepsis / systemic inflammatory disorders
Hormonal
Pregnancy, OCP
Chronic biliary disorders
Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis
Inherited conditions
Biliary atresia, Cystic fibrosis, PFIC

20. Choledocholithiasis (CBD Stones)
Normal
Stones & dilated CBD

21. Alkaline phosphatase (ALP)
Produced in many tissues but raised levels usually come from the biliary epithelium, bones, or placenta.
Raised in children and pregnancy
Unlikely from liver if GGT normal
Cholestasis causes increased synthesis of ALP and “leakage” of ALP in to the circulation

22. Gammaglutamyl transpeptidase (GGT)
Found in cell membranes throughout the body including hepatocytes and biliary epithelium – thought to have a role in AA transport
Levels are not raised in bone disease or pregnancy – unlike ALP
Raised serum levels almost always have a liver origin (usually relating to cholestasis or fatty liver)
Serum levels can be elevated in the absence of liver disease due to enzyme induction by anticonvulsants (phenytoin) or EtOH

23. Causes of hepatocellular damage ( Hepatitis)
Acute
Viral hepatitis
EBV, HAV, HBV
Drugs & herbal remedies
Paracetamol OD
Ischaemic / hypoxic
Rare: Autoimmune (AIH)
Wilson’s disease, BCS, Acute Fatty Liver Pregnancy
Chronic (>6 months)
Viral hepatitis
HBV,HCV
Fatty Liver Disease
NASH / NAFLD
EtOH
Medications
Rare: Haemochromatosis, Wilsons Disease, Autoimmune

24. Alanine Aminotransferase (ALT)
Catalyses the formation of pyruvate in the cytosol
Found in many tissues but by far the highest levels are in the liver (elevated levels are relatively specific for liver disease)
More sensitive marker of liver disease in chronic viral hepatitis than the AST

25. Aspartate Aminotransferase (AST)
Catalyses the formation of oxaloacetate in the cell cytosol and mitochondria.
Found in many tissues but high levels in liver and muscle (cardiac & skeletal)
Elevated levels are not as specific for liver disease as an elevated ALT
Less sensitive marker of hepatic inflammation than ALT

26. Transaminases (ALT & AST)
In chronic liver disease the ALT & AST are usually only mildly elevated (typically x ULN). May be normal.
In most causes of hepatitis the AST / ALT ratio is < 1. Alcohol related hepatitis is the exception where the ratio is usually > 2.
Levels < 10x ULN are non-specific, but there are only a few conditions that cause an ALT or AST > 1000 IU/L

27. Transaminases > 1,000 iU/L
Ischaemic hepatitis (shock)
Acute viral hepatitis (HAV, HBV)
Drugs (Paracetamol OD, halothane, Carbemazepine)
[Alcoholic hepatitis ALT & AST < 300 IU/L]

28. Transaminases (ALT & AST)
The degree of elevation of the does not correlate well with the degree of histological damage in the liver
Levels may go in to the many thousands acutely and the liver recover completely
Falling levels usually denote recovery but are an ominous sign if the liver synthetic function is worsening.

29. Tests of Liver Synthetic Function
Bilirubin
Albumin
Prothrombin Ratio (PR, INR)

30. Bilirubin 80% comes from breakdown of haemoglobin
Taken up by hepatocytes and conjugated with glucuronic acid and excreted in bile
Normally > 95% of serum bilirubin is unconjugated (indirect). Only conjugated (direct) bilirubin can be excreted in the urine.

31. Hyperbilirubinaemia / Jaundice:
In the absence of liver disease isolated unconjugated hyperbilirubinaemia may occur due to over production of bilirubin (haemolysis) or inherited disorders of bilirubin conjugation (Gilbert’s syndrome)
Conjugated (direct)
hyperbilirubinaemia and
bilirubinuria occur only in
hepatobiliary diseases

32. Bilirubin - Prognosis
Poor sensitivity for detecting liver dysfunction.
Large reserve capacity of the liver to remove bilirubin without the development of hyperbilirubinaemia.
In acute cholestatic disease (such as choledocholithiasis) when the hepatocyte synthetic function is normal and the degree of hyperbilirubinaemia does not influence prognosis.
In viral hepatitis, alcoholic hepatitis and PBC the serum bilirubin does correlate with the degree of injury on biopsy and the prognosis

33. Albumin
Made in the liver. Quantitatively the most important protein in the blood (500g in body fluids), important role in maintaining colloid osmotic pressure.
Up to 30g / day can be synthesised in a normal liver
Serum albumin level is
determined by the rate of
synthesis, rate of loss /
degradation and the volume
of distribution.

34. Albumin
A low serum albumin is a good indicator of liver synthetic failure in the presence of chronic liver disease, however other causes of hypoalbuminaemia need to be considered:
Renal loss (Nephrotic syndrome)
Protein-calorie malnutrition
Haemodilution (raised)plasma volume

35. Prothrombin ratio (PR, INR)
Most clotting factors are synthesised in the liver. Liver transplantation is a surgical cure for haemophilia !
In the setting of both acute and chronic liver failure the INR is a very useful indicator of liver synthetic function and prognosis, however other causes of a raised INR need to be excluded:
Vitamin K deficiency (prolonged cholestasis)
Increased clotting factor consumption (DIC)
Warfarin therapy

36. Prothrombin ratio
In chronic liver failure the INR rarely rises above 2.0
In acute or fulminant liver failure the INR may rise rapidly to very high levels (>10), this is associated with a very poor prognosis and liver transplantation should be considered.
Even an INR of 1.3 in the setting of an acute severe hepatitis is of concern and should be repeated after 6-8 hrs

37. Liver Failure Acute (FHF) Chronic (Cirrhosis)
Patient unwell for hours or days
ALT & AST usually > 1,000
INR & Bilirubin rise rapidly
Alb falls rapidly
Death within days of cerebral oedema, sepsis or multi-organ failure
Chronic (Cirrhosis)
Patient unwell for months or years
ALT & AST usually < 200
INR & Bilirubin rise slowly
Alb falls slowly
Death from variceal haemorrrhage, sepsis, encephalopathy or other complications

38. Liver Cirrhosis

39. Cirrhosis
May be the end result of chronic cholestatic or hepatitic disease.
Liver synthetic function may be impaired or normal
The enzymes may be of any pattern or may be normal if the underlying aetiology is inactive or no longer present.

40. Cirrhosis (histopathology)

41. Examination Findings
Asterixis

42. Examination Findings
Dupytrons Contracture

43. Examination Findings
Palmar Erythema

44. Examination Findings
Gynaecomastia

45. Examination Findings
Spider Naevi

46. Grading of ESLD (Child-Pugh Score)

47. Survival according to Child-Pugh Score

48. Cirrhosis - Importance
Why Important?
Hepatoma 1-2% per annum
Variceal Bleeding
Decompensation – Risk of Liver Failure
Suggested By
Bloods
↓Platelets, ↓Albumin, ↑INR, ↑Bilirubin
Clinical Examination
Liver Specific / Other Organ injury
Imaging: USS / CT
Irregular contour, ↑PV size, Splenomegaly, Varices
Endoscopy
Varices, Portal Hypertensive Gastropathy (PHG)

49. Middlemore Hospital Audit - Cirrhosis New patients presenting each year
Gerred et al. 2012

50. Cirrhosis – New Case Aetiology
Gerred et al. 2012

51. Liver Screen FBC LFT’s, CK< TFT’s Coagulation AFP
Hepatitis Serology
A, B, C, D, E
Protein & Ig
Ferritin
Transferrin Sats, HFE
Auto Ab, ANA, Tissue Antibodies, AMA, LKM, SLA
Alpha-1-AT
Copper, Ceruloplasmin
AFP