Autoimmune and metabolic liver disorders

Question 1

Name three autoimmune liver disorders

Answer 1

• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune hepatitis

Question 2

Define primary biliary cirrhosis

Answer 2

Autoimmune progressive destruction of small bile ducts ➔ cirrhosis

Question 3

Which population group is most commonly affected by primary biliary cirrhosis

Answer 3

90% are women aged 40-50

Question 4

How does primary biliary cirrhosis present?

Answer 4

25% are asymptomatic and diagnosed by incidental blood tests

• Fatigue
• Pruritus
• RUQ pain/discomfort
• Later: jaundice, dark urine, pale stools
• Sjogren’s syndrome: Dry eyes and mouth

Question 5

What may be seen on examination of primary biliary cirrhosis?

Answer 5

• Hepatomegaly
• Hyperpigmentation
• Splenomegaly
• Jaundice
• Xanthelasma (late)
• Cirrhosis (advanced disease)

Question 6

Name two risk factors for primary biliary cirrhosis

Answer 6

• FHx
• Multiple UTIs
• Smoking
• Past pregnancy
• Other autoimmune diseases

Question 7

How is primary biliary cirrhosis investigated?

Answer 7

• Anti-mitochondrial antibodies +ve (98%)
• Increased ALP, GGT and mild AST/ALT
• Late: increased bilirubin and PTT, decreased albumin
• Raised IgM
• Liver biopsy to stage disease

Question 8

Outline the management of primary biliary cirrhosis

Answer 8

• Ursodeoxycholic acid
• Colestyramine, rifampicin, naloxone for pruritus
• Fat-soluble vitamin (ADK) supplements
• Bisphosphonates for osteoporosis
• Liver transplantation

Question 9

Define primary sclerosing cholangitis

Answer 9

Progressive cholestasis with fibrosing inflammatory destruction of bile ducts ➔ strictures

Question 10

Which groups are most often affected by primary sclerosing cholangitis

Answer 10

• 60% of cases occur in men aged 35-40
• 70% of patients with PSC also have IBD
• Secondary PSC seen with HIV and cryptosporidium

Question 11

What conditions are heavily associated with primary sclerosing cholangitis?

Answer 11

• Inflammatory bowel disease (70%)
• Hepatobiliary malignancies
• Colorectal cancer

Question 12

Describe the clinical features of primary sclerosing cholangitis

Answer 12

Asymptomatic with abnormal LFTs or hepatomegaly

• Jaundice
• Fluctuating pruritus
• RUQ pain
• Cholangitis
• Cirrhosis (late)

Question 13

What investigations are used for primary sclerosing cholangitis?

Answer 13

• ERCP
• Abnormal LFTs: elevated ALP or GGT typically
• Raised bilirubin (late)
• IgG/IgM raised AMA -ve

Question 14

Outline the management of primary sclerosing cholangitis

Answer 14

• Colestyramine, rifampicin, naloxone for pruritus
• Fat-soluble (ADK) vitamin supplements
• Balloon dilatation/stent for strictures
• Liver transplant

Question 15

Describe autoimmune hepatitis

Answer 15

Progressive inflammatory liver condition of unknown aetiology

25% asymptomatic at diagnosis

May present as an ‘acute hepatitis’:

• Initial:
  
  • Anorexia; nausea; flu-like symptoms
  • May have fatigue and weight loss
• Jaundice

Question 16

What investigations are useful in autoimmune hepatitis?

Answer 16

• LFTs: Very high aminotranferases (AST; ALT)
• FBC:
  
  • Mild normocytic anaemia
  • Thrombocytopenia; leucopenia
• Anti smooth muscle antibodies
• Liver biopsy: mandatory to confirm diagnosis

Question 17

How is autoimmune hepatitis managed?

Answer 17

• Prednisolone
• Azathioprine

Question 18

Name two metabolic liver disorders

Answer 18

• Hereditary haemochromatosis
• Wilson’s disease

Question 19

What is hereditary haemochromatosis?

Answer 19

• Inherited disorder characterised by excess iron deposition
• Casuses fibrosis and functional organ failure
• Associated with HFE gene on chromosome 6

Question 20

What organs may be affected by hereditary haemochromatosis?

Answer 20

• Liver
• Pancreas
• Joints: Osteoarthritis
• Heart
• Skin
• Gonads
• Pituitary
• Adrenals: Addison’s disease

Question 21

Give three presenting features of hereditary haemochromatosis

Answer 21

Often asymptomatic until late stages

• Initially nonspecific:
  
  • Fatigue, weakness
  • Arthropathy
  • Abdominal problems
  • Erectile dysfunction, heart problems
• Diabetes; bronzing of skin; hepatomegaly
• Arthropathy (2nd or 3rd MCPJ)
• Impotence; amenorrhoea; hypogonadism
• Heart failure, arrhythmias
• Cirrhosis

Question 22

Request three investigation for hereditary haemochromatosis

Answer 22

• Serum iron
• Serum ferritin; transferrin saturation
• LFTs - often normal
• Genetic testing
• Liver biopsy - assess extent of tissue damage

Question 23

Outline the management of haemochromatosis

Answer 23

• Avoid iron-containing vitamin preparations and foods
• Alcohol cessation
• Venesection (therapeutic or maintenance)
• Liver transplant
• Monitor serum ferritin - may indicate biopsy

Question 24

What is Wilson’s disease?

Answer 24

Disorder of excessive copper disposition

In the liver, basal ganglia, and cornea

Question 25

How does Wilson’s disease differ in children and adults?

Answer 25

Typically:

• Liver disease in children and adolescents
• Neuropsychiatric disease in young adults

Question 26

When should Wilson’s disease be suspected?

Answer 26

• Any child or young adult with unexplained liver abnormalities
• Patients with movement disorders

Question 27

Give four presenting features of Wilson’s disease

Answer 27

Copper deposits in the liver, basal ganglia, and cornea:

• Acute liver failure, chronic hepatitis, cirrhosis
• Severe depression, neuroses
• Asymmetrical tremor, dysarthria, ataxia, excess salivation
• Kayser-Fleischer ring (95%)

Question 28

How is Wilson’s disease investigated?

Answer 28

• Low serum copper and caeruloplasmin
  
  • Copper binds to caeruloplasmin
• Increased urinary copper
• Liver biopsy

KF rings + low serum caeruloplasmin are sufficient to diagnose

Question 29

Outline the management of Wilson’s disease

Answer 29

• Lifelong penicillamine
• Trientine and/or Zinc for maintenance/asymptomatic