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:

• 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)

HaemolyticCan be intra or extra vascular.

Evidence for haemolysis:↑ unconjugated bilirubin↓ plasma haptoglobin↑ Urinary urobilinogen↑ LDHReticulocytosisSpherocytesSickle cellsRed cell fragmentsCoombs test

Intravascular haemolysis:↑ Plasma HbHaemosiderinuria↓ 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 • 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• 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.

• 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

• 50yr old woman with incidental blood tests. All normal apart from isolated elevated bilirubin. Conjugated/unconjugated levels confirm ↑ unconjugated levels. Δ Gilberts.

• 15 yr. old boy with isolated ↑ ALP. Δ Normal bone growth.

• 26 yr. old 32 week pregnant woman with isolated ↑ ALP. Δ Placental ALP

• 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.

• 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.

• 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.