37. Autoimmunity and the Liver Flashcards
What are some parasitic infections of the liver? What do they cause?
schistosoma mansoni
clonorchis sinensis (chinese liver fluke)
entamoeba histolytica
granuloma formation
(not sure if this is high yield..)
What is the nautral response that a mature immune system respond to HBV infection?
What if the response is too strong?
What happens if it fails to eradicate it?
HBV infects hepatocytes, HBcAg is expressed on the surface.
HBcAg is presented on MHCI, cytotoxic (CD8) T cells recognize it and attacks and destroys the hepatocyte.
HLA class II also present viral core peptides to helper (CD4) T cells, which ultimately goes on to stimulate stimulate antibody production.
Once the immune system clears the virus, immunity follows with development of anti-HBs against HBsAg.
too strong: acute hepatitis or death
failure to eradicate: chronic inflammation persists, and will likely result in progressive scarring, cirrhosis, and ultimately HCC
What is the nautral response that a immature immune system respond to HBV infection?
How is the infection normally transmitted?
What popluation does this normally affect?
What would a liver biospy show?
HBV infects the hepatocyte, but “cohabitates” with the hepatocyte rather than initiating inflammation “immune tolerance”.
occurs in infants: HBV is transmitted via HBV-carrying mothers
Liver Bx: normal or near-normal
What is “immune tolerance”?
state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response.
How would you treat EBV infection?
Why must you titrate the dose carefully?
INTERFERON – works by directly killing HBV and enhancing HLA class II expression on the hepatocyte surface, therefore promoting T cell recognition and elimination of the infected cells
ADR: if the immune system is suddenly too “activated” this may cause too many hepatocytes to be killed off at a time can cause a potentially fatal outcome
What causes HBV reactivation?
PREDNISONE
patients with inactive chronic HBV infection may require prednisone for treatment of another illness. But prednisone can greatly enhance HBV replication, which may result in a fulminant active HBV infection
reactivation can also occur with renal failure, HIV infection, or chemotherapy
What causes Autoimmune Hepatitis (AIH)?
Unknown etiology, but is associated with HLADR3/DR4
Cell mediated (T cell) attack against hepatocytes
What are some symptoms of AIH?
Sx of hepatic failure:
dark urine, RUQ pain, generalized myalgias, anorexia, diarrheahepatomegaly, spider nevi, palpable spleen, scleral icterus
What are the two types of AIH?
Type I “classical” – ANA +/- SMA
Type II – Anti-LKM (liver kidney microsomal ab)
What is the initial treatment for AIH?
What if it’s not responsive to the initial treatment?
Prednisone + Azathioprine
if responsive, taper prednisone, but maintain patient on azathioprine for 2-4 yr (or lifelong if relapses occur when patient is off Rx)
6MP if azathioprine failed or not tolerated
Why must you be wary of if you give prednisone to a patient AIH?
they may have a concurrent HBV infection (remember that prednisone increases risk of reactivation!!!); must use in combination with anti-viral agents
What are some characteristic features/markers of AIH?
If you get all 8, I will buy you a drink after finals :)
- RESPONSIVE to prednisone/immunosuppressants
- ANA (anti-nuclear antibodies)
- SMA (smooth muscle antibodies)
- Polyclonal gammopathy IgG>IgM>IgA
- Increased transaminases (low AP:AST ratio)
- decreased albumin
- increased bilirubin
- prolonged PT/INR
What does the liver biopsy show for AIH? (5)
- interface hepatitis (piecemeal necrosis) - inflammation and erosion of the hepatic parenchyma at its junction with portal tracts or fibrous septa.
- bridging necrosis
- plasma inflammatory infiltrate can be prominant
- lobular inflammation, rosetting of liver cells
- normal bile ducts
Quick association: Anti-smooth muscle antibodies
AIH (anti-SMA)
Quick assocation: piecemeal necrosis (interface hepatitis)
AIH
What is Primary Biliary Cirrhosis (PBC) also known as?
“vanishing bile duct disease”
Quick association: AMA
Primary Biliary Cirrhosis - “vanishing bile duct disease”
Anti-mitochondrial antibodies (ANA)
What is the etiology of primary biliary cirrhosis (PBC)?
How does it occur?
Unknown etiology
Immune-mediated attack that leads to the destruction of SMALL bile ducts (cholangiocytes) -> progressive development of biliary cirrhosis -> Portal HTN -> complications of Portal HTN (cirrhosis)
What are some symptoms of PBC?
Drinks if you get all 8
wide range
- aysmptomatic
- itching (due to high bilirubin) -> excoriations
- fatigue
- hyperpigmentation (due to melanin, NOT jaundice)
- RA symptoms (arthritis, Sjogren’s Syndrome, Limited Scleroderma (CREST))
- jaundice (late manifestation)
- xanthomas/xanthelasmas
- hepatosplenomeagly (due to portal HTN)
What is the hyperpigmentation in Primary biliary cirrhosis due to?
MELANIN, not bilirubin
What is the prognosis of PBC?
bad.
slowly progressive cholestasis, that eventually leads to cirrhosis and liver failure
What is the long-term risk/complications of PBC?
- hepatic osteodystrophy - metabolic bone disease (osteoporosis or osteomalacia)
- hypercholesterolemia
- fat malabsorption (with advanced PBC)
- UTIs
- thyroid dysfunction, CREST, Raynaud’s, Celiac’s RA
How do you treat PBC?
What has not been shown to work?
Ursodoexycholic Acid (UDCA) - increase transport of intracellular bile into the canaliculus, thereby reducing intracellular hydrophobic bile acids – may be cytoprotective)
**immunosuppressive agents have not been shown to be beneficial **
What are some diagnostic features of PBC? (5)
**MAMA **
- AMA
- IgM
- ANA (same as AIH, but also used here?)
- (+) cholestatic liver tests (increased AP/GGT)
- hyperlipidemia
What are some diagnostic features of PBC? (3)
- vanishing bile ducts
- florid duct lesion – inflammatory cells surrounding the bile duct with duct-infiltrating lymphocytes
- granulomatous (epithelioid) aggregates develop near or around bile duct
What is Primary Sclerosing Cirrhosis (PSC) strongly associated with?
ULCERATIVE COLITIS
must know…
What is PSC?
What is the etiology of PSC?
Immune-mediated attack that leads to the destruction of MEDIUM and LARGE bile ducts; ultimately leads to biliary cirrhosis
etiology unknown, but because it is strongly associated with UC, it suggests that PSC is an autoimmune disease.
What are some complications of PSC? (6)
- Cholestasis associated problems
- Pruritis
- Metabolic bone disease
- Malabsorption of DEAK
- Bilary strictures
- Bacterial cholangitis
- Cholangiocarcinoma
- Colon Cancer (in patients with concomitant UC)
- End stage liver disease/portal HTN
How is PSC diagnosed?
cholestatic liver tests
liver biospy
What are some features of PSC seen on a liver biopsy?
- “peri-cholangitis” - expansion of portal triad with a inflammatory infiltrate of lymphocytes and eosinophils
- sclerosing cholangitis – onion skinning/concentric fibrosis around large bile ducts “peri-ductular fibrosis” accompanied by altered biliary epithelium; may be the initial appearance of UC
What would you see on ERCP of patients with PSC?
“beading” (both strictures and dilations of both intra-/extra-hepatic bile ducts
What this be?
AIH
Note
- interface hepatitis (piecemeal necrosis) - inflammation and erosion of the hepatic parenchyma at its junction with portal tracts or fibrous septa.
- bridging necrosis
- plasma inflammatory infiltrate
- lobular inflammation, rosetting of liver cells
- normal bile ducts
What this be?
PBC
- vanishing bile ducts
- florid duct lesion – inflammatory cells surrounding the bile duct with duct-infiltrating lymphocytes
- granulomatous (epithelioid) aggregates develop near or around bile duct
What this be?
“beading” (both strictures and dilations of both intra-/extra-hepatic bile ducts)
What this be?
PSC
- “pericholangitis” - expansion of portal triad with a inflammatory infiltrate of lymphocytes and eosinophils
- sclerosing cholangitis – onion skinning/concentric fibrosis around large bile ducts “peri-ductular fibrosis” accompanied by altered biliary epithelium
