B5.026 Liver Disorders II Flashcards
diseases affecting hepatocytes
hepatitic diseases- viral, autoimmune
fatty liver disease- NASH and alcohol
DILI
hepatocellular carcinoma
causes of viral hepatitis
EBV CMV yellow fever herpes Hep A, B, C, D, E
features of herpes hepatitis
immunocompromised pts
patchy coagulative necrosis, no particular zonal distribution
eosinophilic intranuclear inclusions
3 Ms: multinucleation, molding, margination
features of CMV hepatitis
mostly after renal and liver transplant
immunocompetent people- infectious mono with mild hepatitis
focal hepatocyte necrosis, microabscesses, and occasional sinusoidal lymphocytic infiltration
owl’s eye intranuclear inclusions
features of EBV hepatitis
immunocompetent and immunocompromised people
diffuse sinusoidal lymphocytic infiltrate (string of pearls) with varying degrees of portal inflammation
overview of hep A
endemic in countries with substandard sanitation
fecal-oral contamination- food industry, school, nurseries, raw shellfish
vaccine developed in 1992
no carrier or chronic state
hep A symptoms
sporadic febrile illness with jaundice, fatigue, loss of appetite
what is problematic about how hep A spreads?
it can be shed in feces before an individual shows symptoms, they don’t know they’re transmitting it
epidemiology of hep B
1/3 of world pop have been infected
5% have chronic infection (400 million)
75% of carriers in asia and west pacific
modes of transmission of hep B
high prevalence areas- perinatal transmission during childbirth accounts for 90% of cases
low prevalence areas (US)- sexual contact and IV drugs
vaccination induces protective anti-HBs antibody response in 95%
outcomes of hep B by frequency
65% subclinical disease
25% acute hep B
5-10% chronic hep B
outcome of acute hep B
99% recovery
1% fulminant hep
outcome of chronic hep B
20-30% cirrhosis
2-3% HCC
recovery in the rest
protective antibody against hep B
anti-HBs (antibody against surface antigen)
what determines outcome of hep B infection?
host immune response to virus
strong CD4 and CD8 interferon producing T cells associated with resolution of acute infection
HBV does not cause direct hepatic injury, injury is caused by CD8 cytotoxic T cells attacking infected cells
histo of hep B
ground glass hepatocytes
cells with ER swollen with HSsAg
epidemiology of hep C
3.9 mil have Ab to hep C
75% have chronic infection (viral DNA in serum)
most common blood bourne infection in US
accounts for almost 1/2 of pts in US with chronic liver disease
transmission of hep C
IV drugs - 60% transfusion - 10% prior to 1991 hemodialysis and health care- 5% sexual - 15% vertical transmission - 6%
description of hep D
unique RNA virus that is replication defective
only causes infection when it is encapsulated by HBsAg
dependent on hep B for multiplication
2 types of hep D infection
acute coinfection (simultaneous exposure with hep B) superinfection (exposure of chronic hep B carrier)
hep E overview
enterically transmitted, water bourne
mostly self limiting
high mortality in pregnant women (20%)
4 primary courses of hepatitis
- acute asymptomatic infection with recovery- serologic evidence only
- acute symptomatic hepatitis with recovery
- chronic hepatitis- with or without progression to cirrhosis
- fulminant hepatitis- massive to submassive hepatic necrosis
acute hepatitis on histo
dominant features are in lobular/acinus disordered, "dirty" appearance acidophilic (apoptotic) cells liver plate disarray confluent bridging or submassive necrosis
appearance of sinusoidal lymphocytes
blue dots in typically empty sinusoidal white spaces
clinical definition of chronic hepatitis
persistent inflammatory reaction of the liver with more than 6 months of clinical signs and symptoms
chronic hepatitis on histo
marked and patchy expansion of the portal tracts by predominantly lymphocytes interface hepatitis varying degrees of bile duct damage steatosis lobular inflammation
who gets progressive chronic hep C?
>40 at infection immunodeficient viral heterogeneity genotype 1 males long duration of infection ethanol
grading hep C
activity
- portal inflammation
- interface hepatitis
- confluent necrosis
- apoptosis
staging hep C
fibrosis
what is harvoni?
treats genotype 1 of hep C
one pill, once a day
96-99% of patients who had no prior therapy cured with 12 weeks of therapy
$95,000 for full treatment
appearance of fibrosis on histo
blue strands
blue is bad
can grow to bridge between different areas
clinical signs of cirrhosis
jaundice hypoalbuninemia hyperammonemia hyperestrogenemia coagulopathy encephalopathy hepatorenal syndrome portal hypertension
features of autoimmune hepatitis
young and middle aged women
ANA or anti-SMA usually present
chronic disease, fatal if left untreated
steroid therapy leads to symptomatic improvement
pts with LKM antibody positive diseases have poorer prognosis
diagnosis of autoimmune hepatitis
very complex
multiple factors taken into account
scored based on features
important diagnostic criteria of autoimmune hepatitis
female polyclonal hypergammaglobulinemia circulating autoAb (ANA, ASMA) absence of viral infection, drugs, EtOH favorable response to immunosuppression hepatic rather than a cholestatic liver enzyme profile
autoimmune hepatitis on histo during flare
marked interface hepatitis
lymphoplasmacytic infiltrate
hepatocyte rosettes, emperipolesis
lobular activity
autoimmune hepatitis on histo during quiescent phase
no lobular activity
no to minimal interface activity
mild portal inflammation
what are hepatocyte rosettes
clusters of hepatocytes in a sea of lymphocytic infiltrates
what is emperipolesis
hepatocytes engulf T cells
blue inclusions in hepatocytes
causes of fatty liver disease
alcoholic steatohepatitis
NAFLD
NASH (non-alcoholic steatohepatitis)
what causes steatosis in alcohol induced liver disease
production of excess reducing equivalents (NADH + H+) due to metabolism of alcohol
appearance of hepatic steatosis
small and large fat droplets
initially centrilobular; progressed to entire lobule
reversible with abstinence
histo features of alcoholic hepatitis
hepatocyte swelling and necrosis (ballooning)
Mallory hyaline (ubiquinated cytokeratin intermediate filaments)
neutrophilic reaction
fibrosis
unique feature of fibrosis in alcoholic hepatitis
chicken wire fibrosis
fibrosis around individual cells (usually in zone 3)
2 types of steatosis
macrovesicular (large and small droplet)
microvesicular (VERY small droplets filling hepatocytes)
etiologies of microvesicular steatosis
reye syndrome
fatty liver of pregnancy
valproic acid toxicity
definition of large droplet
fat droplet occupying greater than one half of the hepatocyte
definition of small droplet
fat droplet occupying less than one half of the hepatocyte
not as bad as large droplet
reye syndrome
acute post viral illness in children who are given aspirin for fever
microvesicular steatosis
encephalopathy
due to widespread mitochondrial injury
fulminant hepatitis
hepatic insufficiency progresses from onset of symptoms to hepatic encephalopathy in 2-3 weeks
causes of fulminant hepatitis
drug/chemical -52%
viral (HAV or HBV) - 12%
amanita phalloides (mushroom)
obstruction hepatic veins, Wilson disease, fatty liver of preg, Reye
histo features of APAP overdose
centrolobular necrosis centrolobular hepatocytes (zone 3) contain more microsomal biotransformation enzymes than the peripheral (zone 1) hepatocytes
HCC etiologies
viral infection
alcohol
food contaminants (aflatoxins)
hemochromatosis
what are aflatoxins
from fungus aspergillus flavus
carcinogenic toxins in moldy grains and peanuts
cause mutations in tumor suppressor genes (p53)
when does carcinogenesis occur in the liver
in mitotically active liver
chronic viral hepatitis with recurrent injury and regeneration
features of HCC
can be unifocal, multifocal, diffusely infiltrative
green tinge
invade vascular channels
range from well differentiated to anaplastic
can be trabecular, acinar, solid, scirrhous
2/3 have AFP >1000
majority arise in background of cirrhosis
what are expanded trabeculae
more than 1-2 cells thick between sinusoids
features of fibrolamellar HCC
young woman (20-40 years)
no risk factors
no cirrhosis
better prognosis?
histo fibrolamellar HCC
thick hyalinized fibrous bands
