hep A to G Flashcards
hepatitis clinical presentation?
Ascites
caput medusae
icterus
palmar erythema
teleangiectasia
biochem results?
Causes of Elevated ALT (sGPT) or AST (sGOT) Values in Asymptomatic Patients*
hep and its causes?
A Autoimmune hepatitis
B Hepatitis (A)-B
C Hepatitis C-(G)
D Drugs or toxins
E Ethanol
F Fatty liver
G Growths (i.e., tumors)
H Hemodynamic disorder (congestive heart failure)
I Iron (hemochromatosis), copper (Wilson’s disease) or alpha
1
-antitrypsin deficiency
M Muscle injury
acute vs chronic?
Acute (viral) hepatitis:
asymptomatic
mild icterus, elevated transaminases
severe, prolonged icterus
fulminant hepatitis with liver failure
Chronic (viral) hepatitis:
chronic persisting hepatitis
(virus detectable, few symptoms)
chronic active hepatitis
(continuous tissue destruction)
liver cirrhosis
primary liver cell carcinoma (hepatocellular)
hep clinical pic
hep A virus?
picornavirus, nonenveloped, ss (+) RNA (~10 kbases)
very stable: pH 3 or 60
oC for 10 h
frequently mild or anicteric, „yellow-flu / liver flu“
acute hepatitis, no persistence or chronic outcome
significantly more severe course in chronic hepatitis C
enteral (fecal/oral) transmission, „travel hepatitis“
transmission through contaminated water or raw foods, eg. Oysters (muckeaters…), and in hygienic facilities/ toilets
HAV epidemic in USA (Pittsburgh) from Chi-Chi® food products in the
‚Beaver Valley Mall‘: 490 cases, 3 deaths from liver failure (15.11.03)
(Dead)- vaccine with inactivated HAV (Havrix®: GlaxoSmithKline
Biologicals). The virus (strain HM175) is propagated in MRC-5 human
diploid (lung) cells which were taken from a male fetus aborted at 14 weeks
gestation.
Vaccination recommended for travellers in endemic areas,
and patients with chronic hepatitis B or C. 3 i.m. immunizations (0, 14 days,
6 months), children from 12 months of age.
for immediate / travel protection: passive immunization with
anti-HAV-positive immunoglobulins and/or a 2 step vaccination schedule (0,
4 to 6 months). Basic immunity conferred after the first vaccination
the best way to control hepatitis A infection in the hospital setting is good hygienic practise (re GI viral infections !!!)
hpe a diagnostic marker?
virus in stool, vriema, transaminase increase/icterus (3-9 months)
ttoal anti-HAV (3-12 months)
anti-HAV IgM (3-12 top at 6 months, low at 12 and 3 months.)
Hep E virus?
spherical, non-enveloped, single stranded RNA virus, approximately
32 to 34 nm in diameter.
HEV belongs to a genus of HEV-like viruses (genus Hepevirus).
? preliminarily placed as ‘calicivirus‚ (re GI virus infections)
transmission and clinical properties like HAV:
fecal / oral transmission
usually mild icterus, elevated transaminases
rarely: severe, prolonged icterus, high case fatality in pregnancy
the major etiological agent of enterically transmitted hepatitis
worldwide: especially prevalent in South East Asia and Africa
In 2005 detected in Welsh patients and traced back to PORCINE
HEV…. (part of a Year 3 SSC with NPHS virology and Andrew Godkin)
hep b?
very small ds DNA virus: ca. 3.200 base pairs, Hepadna-Virus
infects only humans and chimpanzees
replication via RNA intermediates using a reverse transcriptase
Pararetrovirus
Enveloped ‚Dane particle‘, filamentous / oval virus-like particles (VLP‘s),
‚Australia antigen
antigen markers for hep b?
hep b markers through months?
diff between acute and chronic hep b markers?
chronic = no anti-HBs
HBsAg is longer.
all the heps and their antigens?
hep b flashcard?
Virus: Hepadna virus, no serotypes, ds circular 3200 bp DNA/RNA chimera
Reservoir tissue: human liver cells
Incubation time: 45 – 180 days (~6 months)
Clinical picture: mostly assymptomatic, icterus: < 5 years: < 10%, > 5
years: 30% - 50%, mortality during acute infection 0,5% - 1%, in
chronic infections < 5 years: 30 - 90%, > 5 years: 2 - 10%. 20%
leading to chronic hepatitis and 0.5% ending in hepatocellular
carcinoma.
Epidemiology: global
Mechanisms of cancerogenesis: unclear (chronic inflammation?)
Lab diagnostics: serology, qual / quant PCR
Prevention: recombinant protein-vaccine: HBsAg from yeast HBvax
Pro®, Aventis Pasteur MSD, combined with inactivated
HAV: Twinrix®,
GlaxoSmithKline Biologicals; combined active-passive vaccination in
HBsAg-positive mothers with unknown status, vaccinations of all
newborns, vaccination of individuals in high risk groups(dialysis
patients, drug abusers)
Therapy: RT inhibitors, eg Lamivudine® (3TC - 2’deoxy, 3’thiacytidine); new
in 2006 entecavir, clevudine, telbivudine
hep D?
Coinfection of HBV with HDV
severe acute hepatitis
low risik of chronic infection
Superinfection
invariably develops into chronic infection
high risik for severe chronic hepatitis
Hepatitis D
Hepatitis D is caused by the Delta agent (Hepatitis D virus: HDV)
HDV is a defective circular small ss (-) RNA virus (1700 bases; viroid-like) and
can only be packaged in the presence of HBsAG in HBV infected cells
=> hepatitis D can only occur in association with HBV infection (satellite virus)
Discovered in 1977 by Dr. Mario Rizzetto and associates in Italy: in
patients affected by Hepatitis B. They observed a new antigen in
hepatitic liver cells different than surface, core and envelope systems that
they called “delta antigen”.
(Gut 18:997-1003,1977)
hep b with HDV superinfection marker?
GOT
HBsAg
HDV RNA
total anit-HDV
no anti-HBs
IgM anti-HDV
hep c virus?
Family: Flaviviridae
Genus: Hepacivirus
Density: 1,03 - 1,2 g/cm3
Size: 50 - 60 nm
Genome: (+) RNA, ~9,6 kb
Properties of the Hepatitis C virus (HCV)
EM morphology of HCV
Cell culture system: Wakita et al. 2005
Genotype 2a strain of HCV, JFH-1
Genotype 2a chimera, FL-J6/JFH
Genotype 1a (Hutchinson strain) H77S: Lemon et al.
In vitro system: Bartenschlager et al. 2003
G418-replicon by Bartenschlager and Rice-mostly
useful for drug screening
risk factors
1.iv
2unclear
3.sexual
hep B risk factors?
- sexual
- oarenteral
- perinatal
diagnostic markersof hep c infection?
HCV RNA
anti-HCV
GOT
hcv genotype?
I. Epidemiology
Confirm patient-to-patient transmission in outbreak investigations (eg
dentist North Wales 2006)
Types 1, 2, 3: global, prevalent in US and Europe
Type 4: Middle east and Africa
Type 5: South Africa
Type 6: Asia
II. Prediction of clinical outcome
Subtype 1b infections are more acute and tend to reinfect liver transplants
Type 2 infections are associated with type II cryoglobulinaemia
III. Genotype-specific treatment response
Type 4 good response
Type 2
Type 3
Type 1 (1b) no treatment response
hep c flah card?
Virus: Flavivirus (Genus hepacivirus), no serotypes, ss (+) lin RNA
Reservoir tissue: human liver cells, suspected dendritic cells
Incubation time: 2 - 26 weeks (~6 months), highly infectious
Clinical picture: mostly assymptomatic, rarely fulminant hepatitis (type
2a/ JFH strain), ~50% leading to chronic hepatitis and up to 7% ending
in hepatocellular carcinoma.
Epidemiology: globally more significant than HIV or HepB
Mechanisms of cancerogenesis:
1. apoptosis inhibition (NS5a)
2. cell cycle effects G1> S (E2 (?), NS5: Rb binding proteins)
Lab diagnostics: serology, qual / quant PCR, genotyping
Prevention: no vaccine approved; peptide vaccine in phase 1 trials,
therapeutic vaccine under development (Biomerieux- MVA vaccine)
Therapy: pegylated interferon alpha combined with ribavirin / genotype
dependent response
hep f
Thus, there is no hepatitis F virus, but the position in the nomenclature
has been occupied for the time being .
hep g virus?
very similar to but distinct from Hepatitis C virus (Flaviviridae):
ss (+) RNA, 10 kb
preliminarily placed into a group of new agents called GB viruses
(GB virus A, GB virus B and GB virus C)
not associated with any acute or chronic liver disease:
benign virus that is widely present throughout the world.
Replicates best in lymphocytes/ not hepatocytes.
no association with poor outcomes of patients who are
infected with Hepatitis C / HIV and Hepatitis G at the same time.
Hep G may actually slow down HepC and HIV
transmitted following receipt of blood from HGV RNA-positive donor
moderate liver enzyme (ALT) elevations.
persistent infection (HGV RNA-positive) for as long as nine years.
route of heps?
