Acute Autoimmune and Metabolic Hepatitis Flashcards
Describe the basic natural history of chronic hepatic cirrhosis.
expansion of inflammation to the portal tracts (interface hepatitis) and this leads to fibrosis that bridges between tracts and causes regenerative nodules in cirrhosis causing disorganization in organ architecture
Who is most likely to get autoimmune hepatitis? What are the most common presenting symptoms?
female predominance, 15-25 or middle aged
fatigue is main symptom, polyarthralgia, jaundice
increased aminotransferases, jaundice, prolonged INR
polyclonal hypergammaglobinemia, positive circulating autoantiboides (not pathogenic) which usually responds to immunosuppressive therapy (prednisone or azathioprine)
Describe the pathogenesis of autoimmune hepatitis.
loss of self tolerance with CTL infiltrate at the portal zones, plasma cells frequently present in large numbers
(pathogenic role of autoantibodies not proven
What type of antibody would you find in type 1, 2 autoimmune hepatitis?
type 1- 80% of cases: ANA anti nuclear antibodies, ASMA anti smooth muscle antibodies
type 2- 4% cases: anti LKM1 Anti liver kidney microsomal (CYP2D6), anti-LC1 anti-liver cytosol (often effects young girls, european)
10% antibodies have no antibodies are found; atypical antibodies: Anti-SLA, pANCA
What other common autoimmune disorders that are common with autoimmune hepatitis.
autoimmune thyroiditis
Grave’s disease
Rheumatoid Arthritis
Ulcerative Colitis
Will liver transplant cure autoimmune hepatitis?
liver transplant will improve liver function but is likely to recur after transplant
What is the inheritance pattern and presenting symptoms of genetic hemochromatosis?
autosomal recessive, chromosome 6 common amongst Northern European ancestry (HFE gene)
cirrhosis, hepatocellualr carcinoma, cardiomyopathy, arthropathy, hyper pigmentation, diabetes, sexual dysfunction
caused by excessive Fe absorption because of low hepcidin (defective transferrin receptor involved in HFE gene)
How does Fe cause liver damage?
lipid preoccupation, cupful cell activation, stelate cell activation, DNA damage, mitochondrial dysfunciton and lysosomal fragility
Describe the inheritance of Wilson’s disease and its presenting symptoms.
“bronze diabetes”
rare autosomal recessive disorder, gene ATP7B, chromosome 13 causes a mutated Cu transporter (P-ATPase) that is present in trans-Golgi network required for excretion of Cu leads to accumulation of Cu in liver, brain, cornea and kidney
leads to acute and chronic liver injury, neuropsychiatric (Parkinson like) disorder, kidney Fanconi syndrome and Kayser-fleischer rings, RBC hemolysis
What lab results would confirm Wilson’s disease.
ceruloplasmin- low
urine copper- high
Kayser-Fleischer rings present
liver tissue copper quantization high
can have mallory bodies on histopathology
How do you treat Wilson’s disease?
chelating agents: trientene, pencillamine
liver transplantation is curative
Describe the inheritance pattern of A-1AT and its clinical presentation.
autosomal co-dominant fashion (normal PiMM, PiZ is the most common deficient variant)
neonate severe hepatitis/cholestatic jaundice
adult: elevate LFTs, cirrhosis, hepatocellular carcinoma
long disease: premature emphysema (most common manifestation )
Describe the pathophysiology of A1-AT.
liver: accumulation of abnormal protein in ER causing cells death, fibrosis and cirrhosis
lung disease: decreased A1AT levels does not inhibit PMN elastase which destroys the elastic tissue around the alveoli
How would you confirm A1-AT dx. What would be the best tx?
serum A1-AT level
phenotype determination
liver biopsy with PAS stain: intracellular globules
tx. with liver transplant and A1-AT admin for lung disease
T/F trasferritin is an acute phase reactant.
nope, ferritin is an acute phase reactant
