Autoimmune liver disease

Question 1

primary biliary cirrhosis (PBC)

Answer 1

intrahepatic bile ducts are damaged by chronic autoimmune granulomatous inflammation
this may cause cirrhosis, fibrosis and portal HTN

caused by a genetic predisposition leading to loss of immune tolerance to self-mitochondrial proteins

typical age at presentation ~50yo
female:male 9:1

ass/w. sjogren’s so can have dry eyes, mouth

Question 2

anitmitochondrial antobodies

Answer 2

AMA

hallmark of PBC

Question 3

PBC presentation

Answer 3

patient often asymptomatic, diagnosed after raised alk phos on routine LFTs
lethargy, sleepiness and pruritus may precede jaundice by years

signs:
jaundice, skin pigmentation, xanthelasma, xanthoma, hepatosplenomegaly

complications:
same as cirrhosis:
hepatic failure - coagulopathy, encephalopathy, hypoalbuminaemia, sepsis, spontaneous bacterial peritonitis, hypocalcaemia
portal HTN - ascites, splenomegaly, portosystemic shunt, including varices, caput medusae, HCC

osteoporosis is also common
malabsorption of the fat soluble vitamins (A, D, E, K) due to cholestasis and decreased bilirubin in the gut. leads to osteomalacia and coagulopathy

Question 4

tests for PBC

Answer 4

blood:
raised alk phos, gamma GT, mildly raised AST/ALT
in late disease: increased bilirubin, decreased albumin, and increased PTT
98% AMA M2 subtype +ive
raised IgM
TSH and cholesterol raised or normal

USS excludes extrahepatic cholestasis
biopsy not usually needed

AMA + raised alk phos –> think PBC

Question 5

Tx for PBC

Answer 5

symptomatic:
Ursodeoxycholic Acid (UDCA)
Hydrophilic bile acid
SE: weight gain, hair thinning and diarrhoea

treat the pruritus with colestyramine
fat soluble vitamin prophylaxis

Question 6

prognosis PBC

Answer 6

survival <2years after jaundice develops without a transplant

Question 7

fat soluble vitamins

Answer 7

boron

Question 8

primary sclerosing cholangitis (PSC)

Answer 8

progressive cholestasis with bile duct inflammation and strictures

signs/Sx:
pruritus, fatigue
if advanced, ascending cholangitis, cirrhosis and end stage liver failure

ass/w. IBD, usually UC of the whole colon
IBD often presents before PSC

typically inactive colitis, but a paradoxically increased risk of colorectal malignancy

raised alk phos, then raised bilirubin
raised IgM
AMA -ive
ANA, SMA, ANCA may be +ive
ERCP distinguishes large duct disease from small duct disease
biopsy shows fibrous, obliterative cholangitis

raised alk phos and ANCA = PSC

Question 9

common sites of cancer in PSC

Answer 9

bile duct
gallbladder
liver
colon

Question 10

Tx PSC

Answer 10

liver transplant is the mainstay for end stage PSC, recurrence occurs in 30%, 5yr graft survival >60%

prognosis worse for those with IBD - 5/10% develop colorectal cancer post transplant

Question 11

autoimmune hepatitis (AIH)

Answer 11

immune attack on hepatocytes
inflammatory disease of the liver of unknown cause
suppressor T-cell defects with autoantibodies directed against hepatocyte surface antigens
primarily affects young and middle aged women (10-30yrs and >40 years)

up to 40 % present with acute hepatitis and signs of autoimmune disease - ie fever, malaise, urticarial rash, polyarthritis, pleurisy, pulmonary infiltration, glomerulonephritis

the remainder present with a gradual jaundice or are asymptomatic and are diagnosed incidentally with signs of chronic liver disease

amenorrhoea common, and disease tends to attenuate during pregnancy

can be triggered by nitrofurantoin and statins

complications: those ass/w. cirrhosis and drug therapy

ANA/ASMA + raised IgG think AIH

Question 12

tests for AIH

Answer 12

serum bilirubin, AST, ALT and alk phos all raised
hypergammaglobulinemia esp IgG, +ive antibodies
anaemia, decreased WCC and platelets indicate hypersplenism

liver biopsy: mononuclear infiltrate of portal and periportal areas and piecemeal necrosis +/- fibrosis
cirrhosis leads to a worse prognosis

an MRCP will help to exclude PSC if alk phos disproportionately raised

Question 13

diagnosing AIH

Answer 13

exclude other diseases, as no lab test is pathognomonic

criteria based on IgG levels, autoantibodies and histology in the absence of viral disease

Question 14

classification of AIH

Answer 14

I. 80%. typical patient, female <40yo, antismooth muscle antibodies (AMSA) +ive in 80%, ANA +ive in 10%, IgG raised in 97%
good response to immunosuppression in 80%
25% have cirrhosis at presentation

II. commoner in europe than USA, more often seen in children, more commonly progresses to cirrhosis and less treatable. antiliver/kidney microsomal type 1 antibodies +ive. ASMA and ANA -ive

III. as type I but AMSA and ANA -ive. antibodies against soluble liver antigen (SLA) or liver pancreas antigen

Question 15

management of AIH

Answer 15

immunosuppressant therapy: prednisolone 30mg/d for 1 month, decrease by 5mg a month to maintenance dose of 5-10mg/d
can sometimes stop corticosteroids after 2 years, but relapse in 50-87%

azatioprine may be used as a steroid sparing agent to maintain remission
remission seen in 80% after 3 years

liver transplant indicated in decompensated cirrhosis or if failure to respond to medical therapy, but recurrence may occur. 10 yr survival 75%

Question 16

AIH associations

Answer 16

pernicious anaemia
UC
glomerulonephritis
autoimmune thyroiditis
autoimmune haemolysis
DM
PSC