Autoimmune Liver Disease

Question 1

When might autoimmune liver disease be suspected from?

Answer 1

-Immunological tests (autoantibodies, immunoglobulins)
-Disease associations (other AI disease, IBD)
-Imaging (in PSC)

Question 2

Pathogenesis of AILD

Answer 2

-Genetics
=MHC (antigen presenting), cytokines

-Environment
=Bacteria
=Viruses
=Toxin
=Drug

==Hepatocyte or bile duct damage

Question 3

Diseases by target cell type

Answer 3

-Hepatocytes
=Autoimmune hepatitis

-Small bile ducts
=Primary biliary cholangitis (most common)

-Larger bile ducts
=Primary sclerosing cholangitis
=IgG4-related cholangitis (relatively rare)

Question 4

Demographics of liver diseases

Answer 4

-PBC= typically 50-60, 9:1 female (strongly female predominance)
-AIH= any age, 5:1 female
-PSC= typically 20-40, males just more common (2:1)
-GgG4= typically 50-60, mainly male (9:1)

Question 5

Describe primary biliary cholangitis

Answer 5

-Granulomatous inflammation around small bile ducts leads to cholestasis
=Raised alk phos and GGT
=Anti-mitochondrial antibody (AMA) 95%
=Liver biopsy required to pick up remaining 5%

-Slowly progressive, can lead to cirrhosis over 15-20 years

Question 6

PBC presentation

Answer 6

-Strong female predominance
-Usually, older patients (50-70)

-Asymptomatic abnormal LFTs
-Itch
-Fatigue

Question 7

PBC investigations

Answer 7

-Cholestatic liver enzymes and AMA sufficient to diagnose in most cases
-IgM often raised
-Stage liver fibrosis (Transient elastography/ fibro scan)
-Measure bien density (DEXA- osteoporosis)

Question 8

Use of Transient elastography for fibrosis

Answer 8

-Liver stiffness correlates with degree of fibrosis
-Used in many liver conditions (disease-specific thresholds)
-Non-invasive, quick, serial measurements

Question 9

PBC treatment

Answer 9

-UDCA= ursodeoxycholic acid
-80% of patients have biochemical response (alk phos)
=Lower response rates in younger patients (20%)= risk of cirrhosis

Question 10

Second-line therapies for non-responders

Answer 10

-Obeticholic acid (FXR agonist)
-Bezafibrate (PPARa agonist)

Question 11

Describe autoimmune hepatitis

Answer 11

-Immune damage to hepatocytes
=Raised ALT
-Can have relapsing remitting course
-No single diagnostic test so can be challenging to identify
-Good response to immunosuppression

Question 12

AIH presentation

Answer 12

-Females> males
-Can present at any age including childhood- peaks 2nd and 6th decades

-Asymptomatic raised ALT
-Fatigue, joint pains
-Jaundice
-Decompensated cirrhosis with no previous symptoms

Question 13

AIH investigations

Answer 13

-Raised transaminases (active disease)
-Positive autoantibodies
=Anti-nuclear antibody (non-specific)
=Anti-smooth muscle (specific)
=Anti-LKM
=Anti-SLA
-Raised IgG (fluctuates with disease activity- higher equals more active)
-Exclude viral or drug causes
-Liver biopsy (confirm diagnosis and stage fibrosis- fibroscan unreliable here)

Question 14

Treatment aims in AIH

Answer 14

-Relieve any symptoms
-In cirrhosis, prevent or reverse decompensation
-In young patients, prevent fibrosis progression

Question 15

AIH treatment

Answer 15

-Initial steroids (glucocorticoids)- get into remission
=Prednisolone
=Budesonide (if non-cirrhotic -portosystemic shunting increases side effects)= steroid high first pass metabolism so less systemic side effects

-Maintenance therapy= azathioprine
=Long-term treatment required (at least 3 years) as high relapse rate on stopping

Question 16

Describe Primary Sclerosing Cholangitis

Answer 16

-Multifocal stricturing of bile ducts (intra-hepatic and/or extrahepatic)
-Autoimmune aetiology based on genetics/ disease associations = does NOT respond to immunosuppression
-Often occurs in association with IBD (colitis)= combination creates high risk of colorectal cancer

Question 17

PSC presentation

Answer 17

-Biliary strictures can cause obstruction
=Raised alk phos/ GGT
=Jaundice (larger bile ducts)
=Itch
=RUQ pain

-Progressive fibrosis can lead to cirrhosis/ portal hypertension
-Cance risk= bile duct, gallbladder, colon

Question 18

PSC investigations

Answer 18

-Usually diagnosed on MRCP
=Multifocal biliary strictures

Question 19

PSC follow up

Answer 19

-No proven medical therapy
-At 1/3 ultimately require liver transplantation

-Screen for cancer and monitor liver function and fibrosis
=Annual colonoscopy (if IBD)
=Annual ultrasound of gallbladder
=No good screening tests for bile duct cancer yet (MRCP or CA19.9)

Question 20

Describe IgG4 cholangiopathy

Answer 20

-Similar inflammatory conditions affecting almost all organs (synchronous or metachronous)
=Pancreas
=Bile ducts
=Salivary or lacrimal glands
=Kidneys
=Retroperitoneal fibrosis

-Characterised by histology showing IgG4-producing lymphocytes/ plasma cells and fibrosis
-Often raised IgG4 levels in blood

Question 21

Describe IgG4 cholangiopathy

Answer 21

-Can mimic PSC or hilar cholangiocarcinoma
-Dramatic response to steroids
=Normalisation of LFTs and scan appearances within a month
-Relapsing and remitting
=Consider long-term immunosuppression

Question 22

Describe Immunoglobulins

Answer 22

-IgM early and transient, IgG late and persistent

-IgG= raised in active AIH, measure of inflammatory activity, normalises with treatment
-IgM= often raised in PBC, remains raised
-IgA= sometimes raised in ALD or NAFLD