3/28 Hepatitis - Wondisford Flashcards
hep A virus
(asymptomatic, acute)
picornavirus
SS RNA virus
- short incubation pd (weeks)
- fecal oral transmission (food/water)
- endemic in underdevpd countries
- outbreaks: daycares, residential spaces
- recover within 6-12mos, usually with no clinical sequellae
- no chronic carrier state
- rarely: fulminant hep → death
dx: IgM anti-HAV in an acute or early convalescent serum sample
prev:
- post-exp: immune globulin to household/institutional contacts
- pre-exp: inactivated HAV vaccine, repeat at 6-12mo
- travelers, military recruit, animal handler, daycare, lab worker, chronic liver disease pts
hep B virus
(blood, birthing, baby-making)
hepadnavirus with:
- surface coat (HBsAg)
- inner core (HBcAg)
- DNA polymerase
partially ds DNA
- endemic in subSaharan Africa, SE Asia (20% of pop)
- needle stick, sexual, perinatal transmission
breakdown
- 90 recover
- 1 fulminant
- 1-2 chronic/carrier state (higher rate in neonates and immunocomp)
- reactivation seen w immunosupp, esp w rituximab
can lead to cirrhosis and hepatocellular carcinoma (esp after chronic inf)
HBV dx
diagnose with
- HBsAg
- IgM antiHBc (indicates recent inf)
- HBV DNA in serum
- post-exp in unvaccinated persons or perinatal exposure in HbsAg+ mom, tx with hep B immune globulin in combo with vaccine
-
pre-exp recombo hep B vaccine
- target: high risk groups
- universal vaccination of all kids recommended in US
hepatitis C virus
(cirrhosis, cancer, carrier)
flavivirus (similar to yellow fever, dengue) w genetic herogeneity
- HCV lacks 5’-3’ exonuclease activity - can’t repair its own replication errors → genetic heterogeneity!
incubation: 8wk
course often milk, marked by fluctuatuing elevations of serium aminotransferase levels
- 50+ chronicity, 20+ cirrhosis (much worse numbers than HBV)
- accounts for 90+ transfusion-assoc hep
- IV drug use accounts for 50+ reported cases
- not a lot of evidence for sexual/perinatal transmission
dx: antiHCV in serium
most sensitive indicator? HCV RNA
hep D virus
(defective, dependent)
defective RNA virus - requires HBV for replication
- either coinfects w HBV or superinfects chronic HBV carrier
- enhances severity of HBV inf via accel of chornic hep → cirrhosis and occasionally fulminant acute hep
spread percutaneously among:
- HbsAg+ IV drug users
- transfusion in hemophiliacs
- HbsAg+ MSM
dx: antiHDV in serum
prev: HBV vaccine in non-carriers
hep E virus
(enteric, epidemic, expectant)
RNA hepevirus
incubation short → gut presentation (like HAV)
self limited, BUT high mortality in preg women (10-20%)
enterically transmitted, responsible for waterborne epidemics in India, Asia, Africa, Central Am
naked viruses
similarities
HAV, HEV lack an envelope = naked viruses
NOT destroyed by gut → affect bowels
“vowels hit bowels”
tx for acute viral hep
basics
fulminant hep failure
acute severe HBV
acute HCV
- high calorie diet, IV hydration (vomiting)
- cholestyramine for pruritis → binds bile acids in int leading to incr uptake of chol
avoid hepatically metabolized drugs
NO ROLE for glucocorticoids
fulminant hep failure? liver transplant
acute severe HBV? antivral tx
acute HCV? delate tx for 6mo with counseling and monitoring of HCV RNA levels
toxin and drug hepatitis
ex. alcohol, CCl4, benzene deriv, muschrooms, acetaminophen
- leads to rapid, predictable necrosis around terminal hepatic venule
- mech may involve toxic metabolite (INH, halothane, phenytoin, methyldopa, carbamazepine, diclofenac, oxacillin, sulfonamides)
- variable onset associated with fever, rash, arthralgias, eosinophilia
alcoholic liver disease
1. hepatic steatosis: macrovesicular fatty change
- may be reversible with alc cessation
2. alcoholic hepatitis: swollen, necrotic hepatocytes with neutrophilic infiltration
- Mallory bodies (intracytoplasmic eosinophilic inclusions of damaged keratin filaments)
- AST>ALT (usually greater then 2:1 ratio)
- requires sustained, long term alc consumption
3. alcoholic cirrohosis: micronodular, irregularly shrunken liver with “hobnail appearance”
- sclerosis around central vein (zone3)
- manifestations of chornic liver disease (jaundice, hypoalb)
- FINAL, IRREVERSIBLE
fulminant hepatic failure
massive hepatic necrosis w impaired consciousness (within two months of onset of illness)
- combo: rapidly shrinking liver size + rapidly rising bilirubin + prolongation of PT (even as aminotransferase levels fall)
high mortality rate (80%)
clinical signs: confusion, disorientation, somnolence, ascites, edema
any hep virus (A-E), rickettsial, dugs/toxins, ischemia, BuddChiari, acute Wilson’s disease, microvesicular fat syndromes (Reye’s, acute fatty liver of preg)
Budd Chiari syndrome
thrombosis or compression of hepatic veins with centrilobular congestion and necrosis →→→
- congestive liver disease (hepatomegaly, ascites, varices, abd pain, fulminant liver failure)
- absence of JVD
- “nutmeg liver”: congestion due to blood backing up from IVC
associated with hypercoagulable states, PV, postpartum state, hepatocellular carcinoma
Wilson disease
hepatolenticular degeneration
recessive mutations in hepatocyte Cu-transporting ATPase (ATP7B gene) → inadequate Cu excretion into bile/blood
presents before 40
- liver disease (hep, acute liver failure, cirrhosis)
- neuro disease (dysarthria, dystonia, tremor, Parkinsonism)
- psych disease
- Kayser-Fleischer rings (corneal deposits)
- hemolytic anemia
- renal disease (Fanconi syndrome)
pathophys
- ceruloplasmin (transports Cu) still secreted into bile/blood, but in a form that lacks copper → rapidly degraded
- free copper accumulates in liver → eventually released and deposited in brain, cornea, kidneys, EBCs, joints
tx: chelation with penicillamine, oral zinc
Reye syndrome
rare, often fatal childhood hepatic encephalopathy
- mito abnormalities
- fatty liver (microvesicular fatty change
- hypoglycemia
- vomiting
- hepatomegaly
- coma
associated w viral infection that has been treated with ASPIRIN (esp VZV, influenza B)
why/how? → aspirin metabolites decr beta oxidation of fat via reversible inhibition of mit enzymes
*avoid aspirin in kids (except w Kawasaki disease)
chronic hepatitis
group of disorders characterized by chronic infl rxn in liver for 6mo
- seen in 60% of pt prev infected with HCV
- clinically mild: waxing/waning aminotransferase elevations
- extrahepatic: cryoglobulinemia w vasculitis, porphyria cutanea tarda, MPGN
etiology: HBV (w or w/o HDV), HCV, drugs (methyldopa, nitrofurantoin, INH, dantrolene), autoimmune hep, Wilson’s hemochromatosis, alpha1AT def
leads to cirrhosis in 30% cases (esp w HDV superinf)
tx: pegylated IFN, antivirals
- all pt with chronic HCV → protease inhibitors (helps avoid cirrhosis)
