18.5 Flashcards
what are general features of autoimmine hepatitis (AIH)
chronic, progressive hepatitis w/ all the features of AI dz:
genetic predisposition, association w/ other AI dz, presence of auto-Ab and therapeutic response to immunosuppression
Sometimes associated w/ relapse and remission
F > M (78%)
There could be a small overlap w/ other AI liver dz (particularly PBC or PSC (more in peds))
what are the HLA associations of AIH
caucasian-DR3,
japanese- DR4,
S. american - DRB1
what immune cells play an important role in AIH
Lymphocytic infiltrate of the liver includes CD4+ and CD8+ T cells at the interface.
CD4+ play imp role in activating B lymphocytes and their differentiation into plasma cells (which produce auto-Ab)
the mechanism by which the interplay of lymphocytes, auto-AB and HLA type lead to liver injury is unclear
what are the 4 features that help determine diagnosis AIH
exclusion of other etiologies,
auto-Ab,
elevation of IgG
supportive histologic findings (lobular hepatitis w/ prominent plasma cells).
( Cant base the Dx off only auto-Ab bc they do not correlate well w/ dz severity or outcome, they may not be present, &/or they present in other dz’s as well. This is why you need the clinical, serologic and histologic features for accurate diagnosis.)
what are the differences btn type 1 and type 2 AIH
type 1 MC in adults- seen w/ ANA, SMA, anti-SLA/LP
type 2 MC in children- seen w/ anti-LKM-1 against CYP2D6 and ACL-1
how do you tx AIH
immunosuppression w/ prednisone w/ or w/o azathioprine, leading to remission in 80-90% pts w/i 12 months
Other medications are used to deal w/ SE of steroids
If pt has an incomplete response or multiple remissions they have a higher risk of cirrhosis and HCC
May need liver transplant in cirrhotic pts.
what is the presentation of AIH
range from asymptomatic (detected w/ increase AST/ALT) to acute/chronic presentations.
Pt w/o symptoms or acute presentation often have fibrosis and possible cirrhosis upon Bx - indicating existence on subclinical dz that went unrecognized
Acute may look like acute viral/drug-induced hepatitis and lead to acute liver failure.
Presentation is commonly insidious w/ nonspecific symptoms- fatigue, anorexia, nausea, abd pain
compare/contrast PBC & PSC
age
gender
clinical course
associated conditions
serology
radiology
duct lesions
what are the two types of AI cholangiopathies
primary biliary cirrhosis (PBC)
primary sclerosing cholangitis (PSC)
what is PBC and how does it occur
inflam destruction of small/medium intrahepatic bile ducts.
result of T lymphocyte-mediated attack on small interlobular bile ducts.
Possibly due to environmental trigger in genetically susceptible pt.
May lead to auto-Ag on bile duct epithelial cells → destroy T lymphocytes.
Cirrhosis can happen bc the retention of bile salts dues to duct injury
what is the prevalence of PBC
F > M (9:1)
peak btn 40-50 y/o.
MC found in the NE USA and N. Europe & LEAST in Africa and India.
Genetic components since family members w/ PBC - increase risk
Associated w/ sjogren, scleroderma, thyroid dz, RA, raynaud’s phenomenon and celiac dz
how does PBC present
Asymptomatic pt found w/ elevated ALP
Symptomatic pts presents w/ increasing fatigue & prurutits.
Advanced dz can cause splenomegaly and jaundice;
others features = skin hyperpigmentation, xanthelasmas, steatorrhea, Vit D malabs - osteomalacia or osteoporosis.
Chronic PBC → HCC.
= slow, progressvie disorder that can lead to end-stage liver dz over a period of 15-20 yrs
what are characterisitic findings and diagnostics for PBC
hypercholesterolemia & most characteristic finding = anti-mito Ab against PDC-E2.
Dx if 2 of the following are present: increase ALP for >= 6 months, (+) anit-mito Ab and/or histologic findings.
Characteristic histology features interlobular bile ducts destroyed by is lymphocytic inflam w/ or w/o granuloma (florid duct lesion)
how do you treat PBC
Ursodeoxycholic acid (natural bile acid) to slow the progression
If Tx fails, liver transplantation is recommended.
what is PSC and how does it occur
inflam/obliterative fibrosis of large intra/extrahepatic ducts & dilations of preserved segments.
Connection w/ UC- T cells activated in damaged mucosa w/ UC, migrate to the liver and recognize cross-reacting bile duct Ag. Infxns/changes in intestinal microbiome thought to cause change in cholangiocytes that incite inflammatory injury
