Autoimmune liver disease

Question 1

What age does autoimmune hepatitis typically present in

Answer 1

40-60 years

Question 2

What HLA types are associated with AIH

Answer 2

HLA DR3 = early onset, more severe disease

HLA DR4 = type 1 AIH, later onset, better response to steroids

Question 3

What are the two types of AIH and associated antibodies

Answer 3

Type 1 (Classic)

• adolescents and adults
• ANA, ASMA, anti-actin antibodies, anti-SLA/LP, p-anca, AMA

Type 2

• occurs at younger age, generally more severe
• can occur in infants
• anti-LKM-1 ab, anti-LC-1 ab, anti-SLA/LP

Question 4

What other immune diseases are associated with each type of AIH

Answer 4

Type 1
- thyroiditis, graves, UC, RA

Type 2
- type 1 DM, thyroid disease, vitiligo

Question 5

Clinical presentation of AIH

Answer 5

Spectrum from asymptomaric to liver failure

Fatigue, anorexia, itch, nausea, abdo pain

Question 6

Complications of AIH

Answer 6

Cirrhosis, HCC (though lower rates then other causes of cirrhosis) and liver failure

Question 7

Diagnosis of AIH

Answer 7

Abnormal LFTs (aminotransferases higher then cholestatic enzymes)
Elevated serum globulins with a polyclonal (usually IgG) response
Test for range of antibodies
Liver biopsy - interface hepatitis, lymphocytic infiltration in portal tract, hepatic rosette formation

Question 8

Treatment of AIH

Answer 8

Glucocorticoid -60mg of prednisone then taper
Maintenance - azathioprine + lower dose steroid

90% will have improvement in LFTs in 2 weeks
50-90% will relapse after stopping treatment (predicted by histology - normal= lower rates of relapse)

Question 9

What sex is autoimmune hepatitis more common in

Answer 9

Female:male
4:1

Question 10

Outcomes in AIH

Answer 10

30% have cirrhosis at diagnosis, 30-50% develop cirrhosis
5% develop HCC
10-20% need liver transplant
AIH recurs in transplant in 20-30%

10 year survival with treatment 90%

Question 11

Epidemiology of PBC

Answer 11

Rare, 100 per million
Mostly women 90%
Middle age 40-60
Common in Northern Europe and North America

Question 12

Pathogenesis of PBC

Answer 12

Widely unknown

T cell attack on small intra-lobular bile ducts leading to destruction and disappearance

Question 13

Clinical features of PBC

Answer 13

Asymptomatic in 50-60%
Fatigue, puritis
Skin hyperpigmentation due to melanin deposition in 25-50%
Xanthomas, xanthelesma due to high levels of HDL

Question 14

Lab findings in PBC

Answer 14

Elevated cholestatic liver enzymes
Mildly raised transaminases
Bilirubin elevated in late disease
AMA positive in 95%
Commonly raised ANA 70%
High HDL - does not correspond to higher risk of CVD

Question 15

Liver biopsy features in PBC

Answer 15

Portal and periportal inflammation

Bridging fibrosis and cirrhosis

Question 16

Conditions associated with PBC

Answer 16

Sjogrens (40-65%)
Thyroid disease
CREST syndrome
RA
inflammatory arthropathy

Question 17

Criteria for diagnosis of PBC

Answer 17

ALP greater then 1.5 the ULN
AMA positive
Histological evidence of PBC

Without extra hepatic obstruction or other conditions affecting the liver

Question 18

Treatment of PBC

Answer 18

Vitamin supplementation
Restrict dietary fat
Control cholesterol
Consider enzyme replacement

UDCA (ursodeoxycholic acid) reduces progression to end stage disease and increases survival

Liver transplant still used for refractory cases
PBC reoccurs in transplant in 30% after 10 years

Question 19

Prognosis of PBC

Answer 19

Normal life expectancy if diagnosed at early stage

Some progression to cirrhosis, HCC, metabolic bone disease and malabsorption

Question 20

Epidemiology of PSC

Answer 20

Male (70%)
Average age at diagnosis 40 yrs

Associated with UC in 90%

Question 21

Pathology of PSC

Answer 21

Cholestatic progressive chronic liver disease

Inflammation and stricturing of intra and extra hepatic bile ducts

Question 22

Genes associated with PSC

Answer 22

HLA B8

DRw52a

Question 23

Clinical features of PSC

Answer 23

Fatigue, pruritis, RUQ pain, fever with cholangitis

Raised cholestatic liver enzymes and bilirubin
Transaminases less then 300 usually

Associated with pANCA

Question 24

How do you diagnose PSC

Answer 24

Gold standard is cholangiography (MRCP etc.)
Shows characteristic beaded appearance of bile ducts with multifocal strictures

Liver biopsy may support diagnosis but is rarely diagnostic

Question 25

Complications of PSC

Answer 25

Vitamin deficiency (DEKA)
Metabolic bone disease
Biliary strictures
Higher risk of cholangitis and cholelothiasis, highest risk after ERCP
Cirrhosis and portal hypertension
Cancer
- cholangio = 10-15% risk
- gallbladder carcinoma
- HCC
- colorectal ca (independent of UC risk)

Question 26

Treatment of PSC

Answer 26

No treatment slows progression
UDCA can improve symptoms but often get worse symptoms once it is stopped
Dilating dominant strictures
Liver transplant has best outcomes

Question 27

Screening for malignancy in PSC

Answer 27

Annual USS/MRI for gallbladder and cholangio +- ca-19-9

Colonoscopy 1-2 years

Question 28

Clinical features of autoimmune pancreatitis

Answer 28

Recurrent pancreatitis
Obstructive jaundice
Strictures
Pancreatic mass

Question 29

Diagnosis of autoimmune pancreatitis

Answer 29

IgG4 plasma cell infiltrates
IgG4 greater then 2x the ULN
Imaging = diffuse enlarged pancreas, irregularities of pancreatic and bile ducts

Question 30

Treatment of autoimmune pancreatitis

Answer 30

Glucocorticoids

If co-existing autoimmune cholangitis can use azathioprine