Infectous Disorders of Liver Flashcards
What kind of disease does Hep A Virus (HAV) cause?
benign self-limited disease
DOESN’T CAUSE CHRONIC HEPATITIS OR CARRIER STATE
How is HAV transmitted?
fecal-oral via contaminated water, or consumption of raw/undercooked shellfish
HAV characteristics?
SSRNA
How does HAV appear clinically?
the disease is mild or asymptomatic and rare after childhood; confers immunity with IgG
anti-HAV immunoglobulin IgM seen in serum w/onset of symptoms (IgM = acute)
What kind of disease does Hep A Virus (HAV) cause?
can cause a wide spectrum of disease manifestations, with most of the
cases leading to asymptomatic chronic disease or clearance
What are the 5 different forms of HBV induced illness?
- acute hepatitis w/recovery and clearance of virus
- Non-progressive chronic hepatitis*
- Progressive chronic disease ending in cirrhosis
- Acute hepatic failure with massive liver necrosis
- Asymptomatic, ‘healthy’ carrier state
*clinically important precursor for HCC
How is HBV transmitted?
- in high-prevalence areas (africa, asia) = childbirth
- in intermediate-prevalence areas = horizontal (breaks in skin/mucus membranes)
- in low prevalence areas = unprotected sex, IV drug abuse
HBV characteristics?
Partially dsDNA virus
What are the serum markers for HBV?
- HbsAg: appears before sxs, peaks during overt dz, lasts ~12 wks (donated blood screened for this)
- Anti- HBs Ab: doesn’t rise until dz over, about same time HbsAg disappears. IgG form provides immunity
- HbeAg, HBV-DNA, DNA polymerase: all appear after HbsAg, indicate active viral replication
- persistent HBeAg = indicator of continued viral replication, infectivity, probably progression to chronic hepatitis
- Anti-HBc ab- appears before onset of sxs, shows up w/ increased ALT/AST levels
Clinically relevant info about HBV?
- age of infection is best indicator of chronicity (younger = increased probability of chronicity)
- host immune response is main determinant of outcome of infection
- hard to completely cure because of viral insertion into host DNA
How does HBV cause hepatocyte injury?
- indiretly; CD8+ cytotoxic T cells attack infected hepatocytes
What is the morphological appearance of liver in HBV infection?
in chronic HBV, liver biopsy shows finely granular ‘ground glass’ hepatocytes packed with HBsAg
- cells w/ER swollen by HbsAg
Hep C virus characteristics?
- SSRNA virus
- b/c of genomic instability + antigenic variability, there’s no vaccine
HCV infection and clearance?
- milder clinically than HBV, but
- 80-90% of pts develop chronic infection, and 20% get cirrhosis
What are clinical characteristics of HCV infection?
- characteristic repeated bouts of hepatic damage
- chronic HCV infection = persistent elevation in serum aminotransferases (wax and wane, but never normal)
- cryoglobulinemia found in ~35% of individuals w/ CHC
How do you diagnose HCV?
Detect HCV-RNA, which is in the blood 13 weeks during active infection w/ increase in ALT/AST
What is HCV associated with?
- metabolic syndrome (genotype 3)
- can give rise to insulin resistance and NAFLD
Liver morphology in HCV?
- HCV leads to portal lymphoid follicle, bile duct reactive changes and lobular regions of macovesicular steatosis
- chronic HCV shows lymphoid aggregates or fully formed lymphoid follicles; fatty change of scattered hepatocytes
- also can maybe mimic primary biliary cirrhosis (histologically)
Characteristics of HDV?
- external coat antigen of HBsAg surrounds an internal “delta antigen”
How does infection with HDV arise?
- co-infection: following exposure to serum containing HDV and HBV (HBV must be established first for HDV to make virions)
- Superinfection: when HBV carrier is exposed to new inoculum of HDV
What are the phases of HDV superinfection?
Acute phase: active HDV replication and suppresion of HBV with high ALT/AST levels
Chronic phase: HDV repl. decreases, HBV repl. increases, transferase levels fluctuate, dz progresses to cirrhosis and sometimes HCC
Clinical signs of HDV infection? (lab-wise)
- HDV RNA is detectable in the blood and liver just before and in the early days of acute symptomatic disease
- IgM anti-HDV is the most reliable indicator of recent HDV exposure
HEV characteristics?
ssRNA
- self-limiting
- not associated w/chronic liver dz or persistent viremia in immunocompromised pts
How is HEV transmitted?
- enterically transmitted, water-borne infection
- zoonotic, has animal reservoirs (cats, monkeys, dogs, PIGS)
What is the most important characteristic feature of HEV?
causes higher mortality among pregnant women (almost 20%)
What is the morphology of acute hepatitis?
- Lymphoplasmacytic (mononuclear) infiltrate
- ‘Spotty necrosis’ or lobular hepatitis scattered throughout a lobule
- Necrosis: empty cytoplasm, cell membrane ruptures leads to hepatocyte dropout
- Collapsed sinusoidal collagen reticulin framework
- Apoptosis: hepatocytes shrink, become eosinophilic, pyknotic, fragmented
- Lack of portal inflammation
What is the morphology of severe acute hepatitis?
- confluent necrosis of hepatocytes around central veins
- Cellular debris, collapsed reticulin fibers, congestion +/- hemorrhage
- Variable inflammation
- Central-portal bridging necrosis leads to parenchymal collapse
What is the morphology of chronic hepatitis?
- mononuclear portal inflammation
- Mild: inflammatory infiltrates are limited to portal tracts
- Progressive disease: extension of chronic inflammation from portal tracts with interface hepatitis
- Linking of portal & portal-central regions = bridging necrosis
What people are at risk of autoimmune hepatitis?
- caucasians w/ DRB1 allele
- females
What are the types of autoimmune hepatitis?
Type 1 - middle aged older ppl
- ANA, **ASMA* (anti-smooth muscle), ANTI-SLA/LP, AMA antibodies
Type 2 - children, teens
- **Anti-LMK1 (anti-liver kidney microsome-1) abs against CYP2D6
- ACL1 antibodies
What are the phases of autoimmune hepatitis?
early phase: severe parenchymal destruction followed rapidly by scarring (takes years to develop)
-shows hepatocyte ‘rosettes’ in areas of activity
progressive or indolent phase: leads to liver failure
- initial sign is severe hepatocyte injury w/necrosis but little scarring
- chronic: burned out cirrhosis w/little necroinflamm. activity
Clinical progression/signs of autoimmune hepatitis
• Acute onset with fulminant disease in 8 weeks
• Hepatic encephalopathy
• Untreated: 40% mortality in 6 months (both type 1 & type 2 lead to liver failure)
• 40% of survivors have cirrhosis
• plasma cells are a prominent and characteristic component of the inflammatory infiltrate in biopsy specimens showing
autoimmune hepatitis
What is the prognosis of autoimmune hepatitis?
Prognosis: better in adults than in children (delay in diagnosis in pediatric populations)
• 80% of patients respond to immunosuppression for long term survival
• End stage: liver transplant with 75% survival at 10 years, recurrence in 20% of patients
Describe acetominophen toxicity’s effect on the liver
- it’s the most common cause of acute liver failure requiring transplant in the US
- it’s caused by a toxic metabolite produced in CYP450 breakdown in acinus zone 3 hepatocytes (closest to central vein and furthest from portal vein)
- zone 2 tries to compensate and gets injured
What are other drugs that can cause toxic effects on the liver (2 specific)
chlorpromazine: causes cholestasis in ppl who are slow to metabolize it to harmless byproduct
halothane: can cause fatal immune-mediated hepatitis in some ppl exposed on multiple occasions
