Common Causes of Liver
Disease in the UK
Edward Bettany
UK Death Rates under 65 1970-2006
The National Plan for Liver Services UK 2009.
BSG.
Main points arising from this document:
1. Liver disease is the 5th cause of death in the UK (average age of death
59 yrs. 83 yrs. for heart and lung disease or stroke). Upward trend in
mortality.
2. Largely preventable
3. Presentation and mortality occurring at a younger age (5 fold increase
of cirrhosis in 35-55 yrs olds in last 10 years)
4. Majority of treatable disease is undiagnosed.
5. Three main causes: Alcohol, viral hepatitis and obesity.
Common causes of liver disease presentation to
secondary care to me:
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Alcohol
Obesity
Stone disease
Viral disease
Malignant disease
Auto immune
Drugs
Congestive/Occlusive (CCF, Budd Chiari)
Metabolic/Congenital
Investigation and management
• History: Alcohol consumption, viral exposure (surgery,
transfusions, sexual contacts, travel, IVDU etc.), painful
or painless jaundice, recent change to prescribed and
non prescribed medication, weight loss, anorexia,
change in bowel habit etc.
• Examination: Confusion, alcoholic fetor, liver flap, palmar
erythema, spider naevi, gynaecomastia, abdominal
distension (ascites), caput medusa, testicular atrophy,
hepatosplenomegaly, evidence of heart failure,
fever/sepsis.
Investigations
• FBC, Prothrombin time
• Biochemistry
• Viral serology (Hepatitis A IgM, Hepatitis B S Ag, Hepatitis C IgG,
Hepatitis E IgM, CMV and EBV serology, HIV, Herpes Simplex)
• Autoantibodies including LKM
• Immunoglobulins (IgM/IgG)
• Haematinics (Iron studies)
• Lipid profile
• Conjugated/unconjugated bilirubin
• Amoebic/Hydatid, toxoplasmosis, schistosomiasis serology,
• Copper/caeruloplasmin
• Alpha 1 antitrypsin and alpha fetoprotein
• Imaging: USS, CT, MRI, MRCP/ERCP
Jaundice (a sign not a diagnosis)
• Haemolytic (pre hepatic)
• Congenital
• Cholestatic (liver parenchymal and
CBD obstruction)
Haemolytic
Can be intra or extra vascular.
Evidence for haemolysis:
↑ unconjugated bilirubin
↓ plasma haptoglobin
↑ Urinary urobilinogen
↑ LDH
Reticulocytosis
Spherocytes
Sickle cells
Red cell fragments
Coombs test
Intravascular haemolysis:
↑ Plasma Hb
Haemosiderinuria
↓ Haptoglobins
Congenital (non Haemolytic)
• Gilbert’s (commonest), Crigler-Najjar
and Dubin-Johnson.
Cholestatic
• Intra hepatic (eg viral hepatitis, drugs, cirrhosis,
alcohol, pregnancy, congenital)
• Extra hepatic (eg stones, carcinoma HOP,
cholangiocarcinoma, bile duct stricture, PSC)
Cirrhosis
• Causes include: Alcohol, Hepatitis B and C, PBC, auto
immune hepatitis, haemochromatosis, hepatic venous
congestion (right heart failure), Budd-Chiari, Wilsons
disease, drugs (eg methotrexate), α 1 anti trypsin
deficiency, cystic fibrosis, intestinal bypass for obesity,
glycogen storage diseases, veno-occlusive disease,
idiopathic.
Examples of what results may show
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Alcohol: Signs. Raised ALP, ALT, Br, PT, focal hepatic lesion on USS,
hepatosplenomegaly, ascites.
Obesity: Raised ALT, fatty liver on USS.
Stone disease: Raised ALP and or ALP and Br, dilated bile ducts on USS
Viral disease: Raised ALT and Br. Positive serology. If chronic, raised ALP, PT and
exclude focal lesions on USS (HCC )
Malignant disease: Raised ALP, Br and focal lesions
Auto immune: Raised ALT or ALP and Br, positive serology, possible focal lesions on
USS (HCC)
Drugs: Variable
Congestive/Occlusive (CCF, Budd Chiari): Variable
Metabolic/Congenital: Usually raised ALP and Br with positive markers for iron or copper
etc.
AUDIT (C)
See hand out
Case Histories
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20 yr. old man with jaundice, anaemia, splenomegaly and leg ulcers. Ix: Hb 9.2, Spherocytes and
reticulocytes on film, ↑ unconjugated bilirubin and urinary urobilinogen, ↓ haptoglobin. Normal ALP,
albumin and Transaminases. Δ Hereditary Spherocytosis.
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44 year old builder has a grand mal seizure spontaneously at home and comes to see you the next
day. He is jaundiced and tremulous and unkempt. He has a 5cm hepatomegaly with spider naevi. His
LFTS reveal ↑ ALT 240, ALP 370, bilirubin 74 and albumin 28. FBC shows Hb 11.8 with MCV 106 and
platelets of 85. What history would you ask? Δ ALD and withdrawal fit
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50yr old woman with incidental blood tests. All normal apart from isolated elevated bilirubin.
Conjugated/unconjugated levels confirm ↑ unconjugated levels. Δ Gilberts.
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15 yr. old boy with isolated ↑ ALP. Δ Normal bone growth.
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26 yr. old 32 week pregnant woman with isolated ↑ ALP. Δ Placental ALP
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22 yr. old man. Recent return from India backpacking. 2 week history nausea, malaise anorexia and 4
day Hx jaundice. ↑ALT/AST and bilirubin, normal USS. Δ Hepatitis A.
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40 yr. old homosexual IVDU with Jaundice. ↑ALT/AST and bilirubin, normal USS. Δ Hep B (or C).
Case Histories
• 16 yr. old girl General malaise, multiple cervical LN’s, mild jaundice. Δ Likely infectious mononucleosis (EBV).
Monospot/Paul Bunnell to confirm.
• 60yr old ex IVDU man. Jaundice, weight loss, ascites, cirrhotic liver on USS and mass in right lobe, ↑ PT and ↓
albumin, normal ALT/AST, +ve Hepatitis B S Ag and e Ag. ↑α Feto protein. Δ Cirrhosis and likely HCC.
• 48 yr. old woman with background history of pernicious anaemia and hypothyroidism (on thyroxine) presents with a 6
month history of general malaise and lethargy. Bloods show adequate TSH suppression but an ALT of 520 with
normal ALP and Bilirubin. USS and hepatitis serology are normal. Next investigation? Δ Auto immune hepatitis.
• 20 yr. old lady who is depressed and tearful following break up of a relationship presents with RUQ pain, low grade
fever and spontaneous bruising. Her PT is raised (INR 3.2) and ALT is 1200. What is the likely diagnosis?
• 60 year old lady with pruritis, xanthelasmata and hepatosplenomegaly is found to have ↑ ALP, IgM and cholesterol on
bloods. Next investigation? Δ Primary biliary cirrhosis.
• 54 year old man with recently diagnosed diabetes who looks tanned and well after returning from a summer holiday
presents with loss of libido and is found to have hepatomegaly. Next investigation? Δ Haemochromatosis
• 30 year old man presents with tremor and dysarthria and involuntary movements. The bloods show a ↑ ALP and a low
plasma caeruloplasmin but elevated urinary copper. Next investigation? Δ Wilsons.
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80 year old man with 2 week history of painless jaundice found to have an ALT of 120, ALP of 700 and a dilated
biliary tree on USS. ΔΔ HOP/cholangiocarcinoma, large CBD stones.