Lecture 39 to 42 Organ tissue infection Flashcards
1
Q
Viral infections of the liver
A
- Hep A to G and TT virus
- Yellow fever virus
- Herpes viruses 1, 3, 4, 5
- Rubella (congenital rubella syndrome)
2
Q
Hep A
A
- naked, icosahedral picornaviridae family
- ss RNA
- resists heating, disinfectants, heating, salt water, stomach pH
- sensitive to chlorine, formalin, and UV
- Etiopath:
- fecal-oral route
- incubation period: 15 to 45 d (short incubation period, infectious)
- Entry: shellfish, oral and anal sex
- virus shedding before sx
- 2 weeks viremia
- virus replicates in Kupffer’s cells and hepatocytes
- Sx: abrupt, sx, fever, nausea, vomiting and jaundice
- recovery complete in 8 to 12 weeks
- non-lytic pircornavirus replicating without much pathology
- damage due to immunpath including CMI, immune complex, and complement
- does not initiate a chronic infectior or liver cancers
- daycare and restaurants
- Dx: ELISA
- Rx: passive Ig
- Control: handwashing, vaccination, inactivated vaccine
3
Q
Hep B
A
- Hepadnaviridae family
- partially ds DNA virus w sphrical, complex envelope w RT
- infected serum has dane particles and viral surface Ag (detectable)
- Etiopath: blood, sex, IV drugs, every bodily fluid is infectious
- strict liver tropism
- genome can integrate into host chromosome
- infected cells release HBsAg particles lacking DNA (just empty shells)
- Incubation period: 50 to 180 d
4
Q
surface antigen (HBsAg)
A
- S, M, L glycoproteins w common C-terminal;
- L-glycoprotein is the attachment protein and alos binds the envelope to the core
- pleomorphic
5
Q
soluble antigen (HbeAg)
A
- associated w core protein, cleavage product of viral core protein; does not assemble into virus; secrete into serum instead
- high HBV titers in serum
- indicator of serum infectivity
6
Q
core antigen (HBcAg)
A
- observed in infected hepatocytes
- has protein kinase activity
- no free HBcAg in serum bc HBcAg -> highly immunogenic -> tyr-arg content high
7
Q
Events during Hep B Acute infection
A
- HBeAg present in serum 1 to 3 mo
- HBsAg prsent in serum 1 to 5 mo
- anti-HBc-Ab 1st to appear
- No HBsAg and HBeAg during window period (5 mo); only anti-HBc Ab in window (Exam q)
- Note: Presence of HbSAg >6 mo = chronic state
8
Q
Development of chronic HBV carrier state
A
- NO WINDOW PERIOD
- viremia continues for years
- HBsAg and HBeAg detectable for years
- anti-HBc-Ab always present
9
Q
Control of HBV infections
A
- screening of all blood for HBsAg
- inactivated vaccines (Hepatavax) and recombinant vaccines (Recombivax) for high risk individuals
10
Q
Hep C
A
- icosahedral, enveloped flavivirus (+ ss RNA)
- HCV only flavivirus not transmitted thru insects
- reservoir: humans & chimps
- 70% persistent infection
- Transmission: sex (20%). IV drugs (60%), blood transfusions
- Incubation 40 to 120 d
- Predictor of disease is high ALT
- Epidemiology: Types 1b and 2 a/c commonly involved in HCC
Etiopath:
- virus coats itself w LDL & VLDL and enters hepatocytes via cell surface receptor
- bud from ER and remains there
- inhibits apoptosis and IFN-alpha by binding to TNF and protein kinase receptors to establish persistence (no cell death)
- proliferation: Beta-catenin/Wnt pathway -> MYC, cyclin D, WISP-2 in nucleus -> cell proliferation
- also core protein -> p21WAF1 (cyclin-dependent) -> inactivates p53
- other than hepatocytes, CD81 and other lymphocytes susceptible
Signs of chronic liver disease
- portal HPT
- jaundice
- scratch marks/pruritis due to obstructive jaundice
- finger clubbing
- palmar erythema
- shifting dullness on percussion of ab due to ascites
- tachycardia to anemia
Control:
- no vaccine bc multiple genotypes
- Pegylated IFN-alpha: Types 2 & 3 more responsive to IFN-alpha therapy than type 1b
- protease inhibitors: Bocepravir & Telaprevir
Rx: curable w combined oral therapy (unlike Hep B)
- Declastavir inhibits NS5A, RNA synthesis, viral assembly/secretion
- Sofosbuvir -> uridine analogue -> binds to NS5B (HCV DNAP)
- Labs: not cirrhotic
- PLT low due to unknown mechanism; splenomegaly
11
Q
Outcomes of HCV infection
A
- IL28B polymorphism alters outcome -> inactive or altered gene -> little/no virus clearance in non-icteric state (see fig.)
- virus persistence
- mitochondria damage -> recruitment of Drp1 -> asymmetric fragmentation -> 1 healthy + 1 damaged mitochondria
- Drp1 -> less interferon production
- Drp1 -> inhibits apoptosis
12
Q
Hep D
A
- -ve ssRNA, circular, enveloped
- 4 genotypes by HLA epitope analysis
- requires presence of replicating HBV which provides the viral coat (containing HBsAg in addition to delta Ag)
- LARGE form HDAg: involved in viral packaging & suppressing HBV replication.
- small form HDAg: transactivating replication of HDV RNA.
- Transmission: blood and IV drugs
- vertical transmission rare but possible
- co-infection w HBV leads to severe and fatal course
- HDV infection subsequent (super infection) to HBV results in milder hepatitis.
- Etiopath: still unclear
- persistent infection assoc. w hepatic inflammation, incr. ALT, and interference of JAK-STAT pathway.
- Dx: anti-delta IgM and/or IgG
- Control: vaccinate high risk against Hep B
- Rx: higher IFN-alpha
13
Q
Hep E
A
- small, naked icosahedral + ss RNA virus
- Hepeviridae family
- Epi: 5 types
- Types 1 & 2: humans (younger Pt)
- 3 & 4: humans, pigs (older Pt)
- 5: birds
- Transmission: fecal-oral, tranfusion, zoonotic
- Epi: contaminated water, S. and E. Asia
- Control: better hygience, no vaccines
14
Q
Hep G
A
- enveloped + ss RNA virus
- flaviviridae family
- transmisible to chimps
- Etiopath:
- causes synctial giant cell hepatitis
- Control:
- no vaccines, source of infection not known
15
Q
Hep TT
A
- icosahedral, naked -ss RNA, circular
- circinoviridae family
- Torque-Tine
- index Pt
- transfusion and dialysis transmitted hepatitis
- Epi: 12% of Japanese and 60-70% of Norwegians have anti-viral Ab
- At least 2 genotypes w many subtypes reported
- Transmission: dialysis, breastfeeding, sex, transplacental
- Control: no vaccines available
