This document provides guidance on evaluating a patient presenting with jaundice. It outlines a systematic approach including focused history, examination, differential diagnosis, and appropriate lab tests and imaging. Liver function tests can indicate hepatitic or cholestatic patterns. Case examples demonstrate applying this approach, such as using imaging and endoscopy to diagnose an ampullary tumor, managing a variceal bleed in cirrhosis, and identifying acute hepatitis B. Key considerations include complications of liver disease and importance of screening high-risk populations.

1. JAUNDICE & LFT INTERPRETATION
Dr. Sharma,Academic F1
Aintree University Hospital

2. LEARNING OBJECTIVES
• To develop a systematic approach to the patient who
presents with jaundice.
• To identify key serological and imaging tests to
request.
• To be able to confidently interpret liver function tests.
• To be able to confidently interpret hepatitis serology
results.

3. FOCUSSED HISTORY (1)
• Presence of abdominal pain
• Painful, colicky → Gallstones? Cholangitis?
• Absence → Cholangiocarcinoma/pancreatic malignancy?
• Obstructive symptoms
• Pale stools
• Dark urine
• Pruritis
• Systemic symptoms
• Fever, chills and rigors → Cholangitis? Biliary sepsis? Hepatitis?

4. FOCUSSED HISTORY (2)
• Risk factors for hepatitis
• Travel history
• Sexual history
• Intravenous drug use
• Risk factors for acute/chronic liver injury
• Alcohol
• Paracetamol
• Other drugs e.g. amoxicillin, flucloxacillin

5. FOCUSSED HISTORY (3)
• Other symptoms of ‘decompensated’ chronic liver disease
(N.B. < 7 days: hyperacute liver failure; 5–12 weeks: subacute liver failure)
• Abdominal swelling (= ascites)
• Episodes of confusion (= encephalopathy)
• Easy/abnormal bruising (= coagulopathy)
• Haematemesis/malaena (= bleeding varices 2° to portal
hypertension)
• Past medical history
• Known chronic liver disease? Known cirrhosis?

6. EXAMINATION (1)
• Apart from the jaundice itself…
• Abdominal tenderness (RUQ pain)
• Organomegaly (hepatomegaly, splenomegaly)
• Signs of acute liver failure
• Bruising (coagulopathy)
• Encephalopathy (asterixis +/- lethargy/confusion)
• Risk factors
• Injection marks
• Tattoos

7. EXAMINATION (2)
• Stigmata of
chronic
liver disease

8. DIF F E R E NT IA L DIA G NO S IS ?

10. ENTEROHEPATIC CIRCULATION OF BILE SALTS

11. PREHEPATIC (OR ‘HAEMOLYTIC’)
JAUNDICE
• Causes
• Haemolytic anaemia (hereditary spherocytosis/elliptocytosis, sickle
cell anaemia, G6PD deficiency, etc.)
• Gilbert’s Syndrome (↑ unconjugated bilirubin)
• Mechanism
• Excessive haemolysis of red blood cells → ↑ unconjugated bilirubin
• ↑ Conjugation of bilirubin in liver {saturation of enzymes}
• ↑ Urobilinogen {forms in SI} → resorbed into circulation → ↑ dark
urine
• ↑ Stercobilinogen {converted from urobilinogen} → ↑ dark stools

12. HEPATIC JAUNDICE
• Causes
• Viral hepatitis (A-E)
• Alcoholic hepatitis
• Ischemic hepatitis
• Drug-induced hepatitis (esp. paracetamol)
• Autoimmune hepatitis
• Malignancy (primary or secondary)
• Decompens ated chronic liver disease {which may have developed as a
result of above – also consider haemochromatosis,Wilson’s disease}

13. POST-HEPATIC JAUNDICE
• Causes
• Any cause of ‘cholestatic’ or obstructive jaundice:
• Gallstones
• Cholangiocarcinoma
• Pancreatic carcinoma
• Primary biliary cholangitis (autoimmune)
• Primary sclerosing cholangitis (associated with ulcerative colitis)
• Parasites
• CONJUGATED BILIRUBIN & LIPASE FROM GALLBLADDER →
BLOCKED ENTEROHEPATIC CIRCULATION
→ PALE, FATTY STOOLS + DARK URINE

15. INVESTIGATIONS (1)
• Routine bloods 💉
• LFTs, yGT (=deranged)
• Glucose (↓ due to ↓gluconeogenesis)
• Clotting screen (PT, aPTT ↑ due to ↓ synthetic function)
• If suspect haemolytic anaemia → ↑ LDH, ↑ haptoglobin
• ABG
• pH is used as part of King’s College transplant criteria for ALF (hepatic
dysfunction is a cause of lactic acidosis)
• Non-invasive liver screen

16. ALBUMIN
• Marker of synthetic function of liver
• But also, a…
• Marker of nutritional status
• Marker of inflammation/disease severity
• Negative acute phase protein
• ↓ production by liver so more amino acids available for
production of positive acute phase proteins
• ↑ proteolysis (catabolism)
• ↑ transcapillary escape rate

17. N.B. ALT is liver-specific,AST is not. yGT may be helpful in confirming that source of raised ALP is the liver.
A ‘cholestatic’ liver function test profile can be caused by intrahepatic causes of jaundice.

18. ‘PATTERNS’ OF LIVER FUNCTION TESTS
‘Hepatitic’
• Hepatocellular damage →
hepatocyte release of
enzymes
• Transaminitis ↑ ALT ↑ AST
‘Cholestatic’
• Obstructed outflow
• ↑ ALP ↑ yGT
A ‘mixed’ picture is also possible
e.g. hepatitic liver damage can lead to obstruction

19. ALT ↑ ↑ ↑ ↑
(THOUSANDS)
• Toxin/drugs ☠️ e.g. paracetamol
• Acute viral hepatitis
• Ischemic hepatitis
• Autoimmune hepatitis
(not really for alcoholic hepatitis, NAFLD,
hepatocellular carcinoma, Wilson’s disease, chronic
viral hepatitis, cirrhosis…)

21. ANTIBODIES
• ↑ anti-mitochondrial
antibodies (AMA)
→ Primary biliary
cholangitis (PBC)
• ↑ anti-smooth muscle
antibodies (A-
SMA)/antinuclear antibodies
(ANA)
→ Autoimmune hepatitis
• ↑ anti-neutrophil cytoplasmic
antibodies (ANCA)
→ Primary sclerosing
cholangitis (PSC)
associated with ulcerative
colitis

22. SEROLOGY
Constant region of antibody varies by heavy
chains
IgM: 1st class produced during antibody
response; binds and agglutinates
microorganisms early in response; production
of large immune complexes
Production downregulated with generation of
IgG
IgG: binds to C1w and receptors on
phagocytic cells; gain access to extravasci;ar
spaces

26. N.B. HbeAg (the envelope antigen) and anti-HbeAg play an important role in indicating
disease activity in patients with chronic hepatitis.

28. CHILD-PUGH SCORE

29. INVESTIGATIONS (2)
• Imaging
• Abdominal ultrasound
• Liver echotexture (cirrhotic? Helps differentiate acute vs. chronic damage)
• Focal lesions (mets?)
• Biliary obstruction (CBD/extrahepatic/intra-hepatic duct dilatation)
• Gallstones
• Portal vein patency (thrombosis?)
• CT
• MRCP

30. INVESTIGATIONS (3)
• Fibroscan (transient elastography) – measures liver stiffness and allows gradation
of fibrosisWITHOUT need for liver biopsy!
• Intervention
• Endoscopic Retrograde Cholangio-pancreatography (ERCP) (balloon
trawling, stenting, sphincterotomy)
• PercutaneousTranshepatic Cholangiogram (PTC)

32. ASCITIC TAP
• EVERY PATIENT PRESENTING TO
HOSPITAL WITH ASCITES SHOULD
HAVE AN ASCITIC TAP.
• This is to rule out SPONTANEOUS
BACTERIAL PERITONITIS, which can
be asymptomatic.

33. ANALYSIS OF ASCITIC FLUID

34. CASE 1
• A 75-year old lady presents with a 4-week history of jaundice, 3 kg
weight loss, pale stools, and dark urine. She has not experienced
any abdominal pain. She has no past medical history.
• On examination, she is jaundiced but apyrexial.The remainder of
her observations are normal. Her liver edge is palpable at 2-cm
below the costal margin. She has no signs of chronic liver disease.

35. BLOOD TESTS
• FBC
• Hb 135 g/L
• WCC 4.5 x 109/L
• Platelets 124 x 109/L (↓)
• U&Es
• Normal
• LFTs
• Bilirubin 240 uM ↑
• ALT 120 IU/L (↑)
• ALP 1506 IU/L (↑ ↑)
• Albumin 36 g/L
• Clotting
• INR 1.3

36. QUESTIONS (1)
• What pattern of LFTs is demonstrated here?
• Obstructive
• Differential diagnosis?
• Pancreatic head tumour
• Ampullary tumour
• Cholangiocarcinoma
• Gallstones
• Benign biliary stricture

37. QUESTIONS
• Next steps?
• Imaging
• CT abdomen, pelvis and thorax → dilated
CBD @ 12 mm, with mildly dilated
intrahepatic ducts
• Dilated pancreatic duct
• No gallbladder stones
• No visible lesion in head of pancreas, no
evidence of lymphadenopathy or metastasis
“Double duct” sign:
simultaneous dilatation of
pancreatic and bile ducts,
suggestive of pancreatic or
ampullary tumour

38. QUESTIONS
• Next steps?
• ERCP
• Double duct sign observed again
• Appearances suggestive of ampullary carcinoma → biopsies
obtained
• Biliary stent inserted
• Prophylactic antibiotics commenced post-ERCP (↑ risk of
cholangitis)
• Management
• Local resection orWhipple’s procedure (pancreatoduodenectomy)

39. CASE 2
• A 52-year old retired army major, with a background of alcoholic liver cirrhosis
andType II diabetes mellitus, is brought in by his wife. He presents with
worsening jaundice, recurrent haematemesis and malaena over the past 3 days.
He has no previous hospital admissions.
• On examination, he appears unwell. Heart rate is110 bpm, BP 95/55 mmHg,
oxygen saturation 95% on room air, and temperature 35.8C.
• There are multiple signs of chronic liver disease. He is alert and mildly confused,
with asterixis and mild ascites present.
• His drug history includes metformin and spironolactone.

40. BLOOD TESTS
• FBC
• Hb 72 g/L (↓)
• WCC 7.1 x 109/L
• Platelets 83 x 109/L (↓)
• U&Es
• Na+ 136 mM
• K+ 4.6 mM
• Urea 9.1 mM (↑)
• Creatinine 110 uM (baseline 83)
• LFTs
• Bilirubin 212 uM ↑
• ALT 300 IU/L (↑)
• ALP 100 IU/L ↑
• yGT 320 IU/l ↑
• Albumin 32 g/L (mildly ↓)
• Clotting
• INR 1.8

41. QUESTIONS (1)
• Differential diagnosis?
• Decompensated alcoholic liver disease
• UGI bleed
• Variceal bleed (must exclude as has signs of portal hypertension - ascites!)
• Peptic ulcer
• CHILD-PUGH Score?
• 11 (Class C – severe, decompensated disease)
• Glasgow-Blatchford Score?
• 15

42. QUESTIONS (2)
• Initial management?
• IV access and fluid resuscitation
• X-match 2 units RBC (aim 70-90 g/L)
• IV Terlipressin 2 mg STAT, then QDS
• IVVitamin K 10 mg STAT
• Prophylactic antibiotics for variceal bleeds (tazocin @
Aintree)
• Urgent gastroscopy

43. CASE (CONT.)
• Gastroscopy showed four oesophageal varices protruding
halfway across the lumen.
• Seven variceal bands were applied, with a good result.

44. QUESTIONS (3)
• Subsequent management?
• Treatment of hepatic encephalopathy:
• Lactulose 10-20 mL TDS (aim BO 3 x / day)
• Rifaximin 550 mg TDS
• Prophylaxis for variceal bleeding (non-selective beta-blocker once BP
stable):
• Carvedilol 6.25 mg OD or propanolol 40 mg BD
• Treatment of ascites (N.B. should’ve been tapped on admission!):
• Spironolactone 50 mg BD
• Paracentesis, if required

45. CASE 3
• A 36-year old businessman, with a history of intravenous
drug use, presents with a 2 day history of jaundice, fever,
chills and general malaise. He does not complain of
abdominal pain.
• He has a past history of sexual intercourse with other
men, and has previously been diagnosed with HIV (on
antiretroviral therapy).
• On examination, he appears jaundiced, and a liver edge is
palpable. He is mildly tender in the right upper quadrant.
Observations are otherwise normal.

46. BLOOD TESTS (1)
• FBC
• Hb 145 g/L
• WCC 5.4 x 109/L
• Platelets 220 x 109/L
• U&Es
• Na+ 140 mM
• K+ 3.9 mM
• Urea 5.2 mM
• Creatinine 75 uM (baseline 80)
• LFTs
• Bilirubin 110 uM ↑
• ALT 1430IU/L (↑)
• ALP 150 IU/L ↑
• yGT 800 IU/l ↑
• Albumin 37g/L
• Clotting
• INR 1.2

47. QUESTIONS (1)
• What pattern do the LFTs show?
• Hepatitic
• What is your differential diagnosis?
• Viral hepatitis (Hepatitis A-E, CMV, EBV)
• Ischemic hepatitis
• Autoimmune hepatitis
• Drug-induced liver injury
• Acute alcoholic hepatitis
• Biliary obstruction
• Primary or secondary hepatocellular carcinoma
• Other congenital causes: Wilson’s disease, haemochromatosis, etc.

48. QUESTIONS (2)
• What further tests would you like to perform?
• US abdomen (?cirrhosis)
• Full liver screen, including viral serology

49. RESULTS (2)
Marker Result
HbsAg +
Anti-HBs (total) -
Anti-HBc IgM ++
Anti-HBc Ig (total) +
In keeping with acute hepatitis B
Next investigations worth ordering would be HbeAg, HBV PCR to
determine viral load, and HBV genotyping.

50. CASE 3 (CONT.)
• This man was referred to a liver specialist for consideration
of antiviral therapy and liver transplantation.
• Treatment for Hepatitis C is otherwise conservative. Patients
commenced on antiretroviral therapy are high risk (e.g.
pregnant), have high viral loads and/or a marked transaminitis.

51. IMPORTANT CONSIDERATIONS
• Recurrent episodes of acute-on-chronic hepatitis B can lead to
cirrhosis.
• Note that the majority of patients will be asymptomatic, and that
a recent multi-centred RCT trial (HepFREE) demonstrates significant
cost-effectiveness to primary-care level screening of hepatitis B and
C in high-risk migrant populations.