Autoimmune liver disease Flashcards
What age does autoimmune hepatitis typically present in
40-60 years
What HLA types are associated with AIH
HLA DR3 = early onset, more severe disease
HLA DR4 = type 1 AIH, later onset, better response to steroids
What are the two types of AIH and associated antibodies
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
What other immune diseases are associated with each type of AIH
Type 1
- thyroiditis, graves, UC, RA
Type 2
- type 1 DM, thyroid disease, vitiligo
Clinical presentation of AIH
Spectrum from asymptomaric to liver failure
Fatigue, anorexia, itch, nausea, abdo pain
Complications of AIH
Cirrhosis, HCC (though lower rates then other causes of cirrhosis) and liver failure
Diagnosis of AIH
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
Treatment of AIH
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)
What sex is autoimmune hepatitis more common in
Female:male
4:1
Outcomes in AIH
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%
Epidemiology of PBC
Rare, 100 per million
Mostly women 90%
Middle age 40-60
Common in Northern Europe and North America
Pathogenesis of PBC
Widely unknown
T cell attack on small intra-lobular bile ducts leading to destruction and disappearance
Clinical features of PBC
Asymptomatic in 50-60%
Fatigue, puritis
Skin hyperpigmentation due to melanin deposition in 25-50%
Xanthomas, xanthelesma due to high levels of HDL
Lab findings in PBC
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
Liver biopsy features in PBC
Portal and periportal inflammation
Bridging fibrosis and cirrhosis
Conditions associated with PBC
Sjogrens (40-65%) Thyroid disease CREST syndrome RA inflammatory arthropathy
Criteria for diagnosis of PBC
ALP greater then 1.5 the ULN
AMA positive
Histological evidence of PBC
Without extra hepatic obstruction or other conditions affecting the liver
Treatment of PBC
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
Prognosis of PBC
Normal life expectancy if diagnosed at early stage
Some progression to cirrhosis, HCC, metabolic bone disease and malabsorption
Epidemiology of PSC
Male (70%)
Average age at diagnosis 40 yrs
Associated with UC in 90%
Pathology of PSC
Cholestatic progressive chronic liver disease
Inflammation and stricturing of intra and extra hepatic bile ducts
Genes associated with PSC
HLA B8
DRw52a
Clinical features of PSC
Fatigue, pruritis, RUQ pain, fever with cholangitis
Raised cholestatic liver enzymes and bilirubin
Transaminases less then 300 usually
Associated with pANCA
How do you diagnose PSC
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
Complications of PSC
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)
Treatment of PSC
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
Screening for malignancy in PSC
Annual USS/MRI for gallbladder and cholangio +- ca-19-9
Colonoscopy 1-2 years
Clinical features of autoimmune pancreatitis
Recurrent pancreatitis
Obstructive jaundice
Strictures
Pancreatic mass
Diagnosis of autoimmune pancreatitis
IgG4 plasma cell infiltrates
IgG4 greater then 2x the ULN
Imaging = diffuse enlarged pancreas, irregularities of pancreatic and bile ducts
Treatment of autoimmune pancreatitis
Glucocorticoids
If co-existing autoimmune cholangitis can use azathioprine
