L19- GI Infections VIII (viral hepatitis, liver parasites) Flashcards
HBV:
- (1) genome, structure, family
- (2) conditions where it is uniquely stable/resistant
- particles are termed (3)
- requires (small/large) inoculation dose
1- partial dsDNA (circular, relaxed), enveloped // hepadnaviridae
2- low pH, resistant to freezing, detergents, moderate heat
3- Dane particles
4- small
HBV structure:
- (1) list important surface Ags
- (2) list important core proteins
1- envelope has 3 glycoproteins: L, M, S (large, medium, small) = HBsAg
2- core protein = HBcAg and reverse transcriptase [note- viral DNA genome is in core also]
HBV is unique because in addition to replicating, it also produces…..(explain)
Subviral Lipoprotein Particles
- 20nm spheres / filaments
- ***contains envelope glycoproteins
- *outnumbers infectious virions 1000-10000:1
-aka decoy particles w/o DNA, non-infectious (although it will produce an immune reponse)
HBV:
- HBcAg = (1)
- HBsAg = (2)
1- core protein / Ag
2- surface glycoprotein (on envelope): either L/M/S (large, medium, small)
describe HBV replication
1) partial dsDNA –> cccDNA in the nucleus (covalently closed circular DNA)
2) transcription of cccDNA –> 4 mRNA molecules (host machinery)
3a) mRNA –> viral proteins (host machinery)
3b) RNA dep. DNA poly. (reverse transcriptase) converts mRNA –> dsDNA
Note- creation of Dane particles and partial HBV particles
name the function for each HBV protein
- (1) ORF P
- (2) ORF S
- (3) ORF C
- (4) ORF X
1- P, viral polymerase (reverse transcriptase)
2- S, surface protein (L, M, S) –> attachment to liver cells (hepatocytes, Kupffer cells)
3- C, core protein for capsid
4- X, HBx protein –> transactivator to establish infection + HCC development
HBV:
- infects (1) cells
- replication in (nucleus/cytoplasm)
- risk to develop (3)
- can survive outside of body in blood for (4)
1- hepatocytes, Kupffer cells
2- nucleus
3- HCC
4- 7 days
list the routes of HBV transmission
(highest at acute stage of infection, most amount of virions)
- unprotected sex
- contact with infected blood, blood transfusions, open wound
- IV drug use, tattoos, piercings
- vertical: mother to child
- sharing razors, toothbrushes
HBV:
- acute infection mostly in (1) patients
- chronic infection mostly in (2) patients
1- adults
2- children (immuno-compromised)
list the Sxs HBV infections
1st: fever, rash, arthritis (type III hypersensitivity reaction)
2nd: malaise, nausea, anorexia, jaundice, dark urine, RUQ pain
Last: itching
(T/F) HBV directly kills liver cells
F- not directly cytopathic
-MHC-I / CD8 Tc cells directed against HBV Ags –> kills infected hepatocytes
AND
-non-specific inflammatory response
HBV infections will result in Igs against ______ Ag
- HBcAg (core protein)
- HBsAg (surface glycoproteins)
- polymerase
list the techniques used for HBV diagnosis
ELISA, immunochromatographic assay, qualitative immunoassay, and agglutination assay: detects viral Ags (HBsAg, HBeAg, HBcAg) and Igs against viral Ags
qRT-PCR –> HBV titers
Biochemical assays: monitors liver enzymes (ALT, AST) for acute or chronic infections
Liver biopsy: assess liver damage when ALT is high
how is chronic HBV infection defined clinically
> 6mos
persistence of HBsAg in blood
(no window period)
HBV Tx
-IFN
with or without
-anti-virals: polymerase inhibitors as nucleoside / nucleotide analogs
HBV prevention
Vaccines: subunit or immune globulin
- screening blood supply
- elimination of ‘risky’ behavior (sex, IV drug use, etc)
HBV Serology (indicate disease status):
- HBsAg (-)
- anti-HBc Ig (-)
- anti-HBs Ig (-)
susceptible
HBV Serology (indicate disease status):
- HBsAg (-)
- anti-HBc Ig (+)
- anti-HBs Ig (+)
immune via natural infection
HBV Serology (indicate disease status):
- HBsAg (-)
- anti-HBc Ig (-)
- anti-HBs Ig (+)
immune via vaccine
HBV Serology (indicate disease status):
- HBsAg (+)
- anti-HBc Ig (+)
- IgM anti-HBc (+)
- anti-HBs Ig (-)
acute infection
HBV Serology (indicate disease status):
- HBsAg (+)
- anti-HBc Ig (+)
- IgM anti-HBc (-)
- anti-HBs Ig (-)
chronic infection
HBV Serology (indicate disease status):
- HBsAg (-)
- anti-HBc Ig (+)
- anti-HBs Ig (-)
unclear could be:
i) resolved infection, most common
ii) false positive (therefore susceptible)
iii) low level chronic infection
iv) resolving acute infection
HDV:
- (1) alternate name
- (2) genome, shape, family
- (3) important Ags
1- defective virus (HBV = helper virus)
2- enveloped, (-)ssRNA, rod-shaped (extensive base pairing) // deltavirus
3- HBsAg, S-HDAg (small capsid protein), L-HDAg (large capsid protein)
list the HDV clinical manifestations
Co-infection (<5%):
- co-administration of HBV/HDV with HBV infection followed by HDV infection
- low risk of chronic liver disease
Superinfection (70-80%):
- established HBV infection
- HDV administration with immediate infection
- high risk of chronic liver disease
Fulminant hepatitis / acute liver disease (w/ encephalopathy)
HDV diagnosis requirements
detection of the following:
- anti-HDAg
- HDV RNA
- HDAg (acute phase of disease)
HDV Tx and prevention
Tx: IFN-α, no real 100% effective Tx
Prevention: HBV vaccination
list the main parasites for liver and biliary tree infections
(trematodes)
- fascioliasis
- clonorchiasis
- opistorchiasis
Clonorchiasis clinical manifestations…
- cholangitis
- biliary hyperplasia / obstruction
- cholangiocarcinoma
Fascioliasis clinical manifestations
- hepatic fibrosis / necrosis
- cholangitis
- biliary obstruction
- biliary cirrhosis
Opisthorchiasis clinical manifestations
- cholangitis
- biliary hyperplasia and obstruction
- cholangiocarinoma
describe the key trematode features
- unsegmented
- incomplete digestive tract
- two striated suckers
- most are hermaphrodites
- most of the body is reproductive organs
Fasicola hepatica = (1)
Fasicola = (2)
-infects (3) organ
-(4) reservoirs (definitive host), with (5) as intermediate host
1- liver fluke, sheep liver fluke 2- giant fluke 3- liver + biliary passages 4- sheep, goat, cattle, other herbivorous 5- fresh water snails
Fasicola spp.
- (1) is the method of human infection via (2) as intermediate hosts
- (3) form in hosts, leaves host via (4)
1- (incidental hosts) contaminated water OR aquatic plants (watercress)
2- fresh water snails
3- adult worm (intestinal)
4- feces
Fasicola spp. life cycle (pre-host / human):
- (1) form in feces
- forms (2) in water, and (2) invades (3)
- (2) develops into (4) within (3)
- (4) form is release from (3) and infects (5) and becomes (6)
1- immature eggs 2- miracidia 3- (fresh water) snail 4- *cercariae (rediae, sporocysts) 5- aquatic vegetation (watercress) 6- **metacercariae encyst
Fasicola spp. lifecycle (starting with infectious form):
- mammals ingest (1) form from (2)
- (3) conversion occurs in the duodenum
- migration to (4) occurs, and (5) maturation occurs
1- **metacercariae (encyst) 2- aquatic vegetation (watercress) 3- metacercariae excyst 4- liver parenchyma into biliary ducts (via intestinal wall / peritoneal cavity) 5- adult flukes
Fasicoliasis:
- often (a-/symptomatic)
- (2) incubation period
- (3) list the phases
1- asymptomatic (Sxs 15% of time)
2- days - months
3-
acute (larvae, 2-4mos)
–> latent (mos-yrs, asymptomatic, parasite maturation)
–> chronic (adults)
Fasioliasis acute phase: form, duration, Sxs
- migration of larvae (metacercariae)
- 2-4 mos
Sxs:
- general allergic / toxic rxns
- fever, urticaria
- generalized / RUQ abdominal pain, hepatomegaly
- loss of appetite, flatulence, n/d
- cough, SOB, chest pain
Fasioliasis acute phase: form, Sxs
-adult flukes
- biliary colic, RUQ pain, epigastric pain
- nausea, intolerance to fatty food, obstructive jaundice
- pruritus
- biliary lithiasis
Fasioliasis:
- (1) Dx
- (2) geographic prevalence
- (3) Tx
- (4) prevention
1- Ova, stool sample microscopy
2- worldwide
3- antiparasitics
4- use non-contaminated veggies (water/feces) by washing and cooking + control intermediate hosts
Clonorchis sinesis = (1):
- associated with (2) consumption
- (3) 1st host, 2nd host, reservoirs
1- Opisthorchis sinensis // Chines or Oreintal liver fluke
2- raw, pickles, smoked fish
3- fresh water snail –> freshwater fish –> fish + cats, dog, carnivores
C. sinensis life cycle (pre-host / human):
- (1) form in feces
- invades (2) and develops into (3)
- (3) develops into (4)
- (4) form is released and infects (5) and becomes (6)
1- embryonated eggs (shed in feces) 2- (fresh water) snail 3- miracidia 4- *cercariae (rediae, sporocysts) 5- fish 6- **metacercariae encyst
C. sinesis lifecycle (starting with infectious form):
- mammals / humans ingest (1) form from (2)
- (3) conversion occurs in the duodenum
- migration to (4) occurs, and (5) maturation occurs
1- **metacercariae (encyst) 2- fish 3- metacercariae excyst 4- liver parenchyma into biliary ducts (via intestinal wall / peritoneal cavity) 5- adult flukes
list the range of clinical manifestations of C. sinesis infections
1) mild / asymptomatic
2) severe infection: fever, diarrhea, epigastric pain, hepatomegaly, anorexia, jaundice (occasionally)
3) biliary obstruction
4) chronic infection: adenocarcinoma of bile duct
5) Gallbladder invasion: cholescystitis, cholelithiasis, impaired liver function, liver abscess
C. sinesis:
- (1) geographic incidences
- (2) main risk factor
- (3) Dx
- (4) Tx
1- Asia (Korea, China, Taiwan, Vietnam, Japan, Russia)
2- eating infected fish (raw)
3- Ova in stool sample microscopy
4- antiparasites
