Hepatitis Viruses

Hepatitis A

50% of viral hepatitis infections; causes mild hepatitis with a short incubation period

non-enveloped, cubic capsid composed of VP₁, VP₂, VP₃, VP₄ (viral polypeptides)

single serotype; RNA independent – does not use host machinery

genome: single stranded RNA with associated VP_G

transmission: fecal-oral Þ major agent of infectious hepatitis (so, important to immunize families of patients)

common in crowded areas (hospitals, daycare, areas of poor sanitation)
mostly sporadic cases; rare outbreaks associated with shellfish in feces-contaminated waters

childhood infections often asymptomatic; adult infections usually self-limiting

diagnosis:

virus in feces (detectable ~ 2 weeks; before other indicators: Ig, virus in blood, jaundice)
virus specific IgM (first to develop in acute infection ~ 4 weeks)
virus specific IgG (persists after infection, so presence may indicate prior infection, not current)

treatment: immunization before or during incubation period; adequate rest; no hospitalization

outcomes:

childhood infections usually asymptomatic; 25-50% of adults are asymptomatic
50-75% of adults have icteric disease; 99% recover completely
low mortality, low incidence of chronic disease

Hepatitis B

41% of viral hepatitis infections; causes moderate infection with potential to establish persistent infection

enveloped; HBsAg (Hep B surface antigen) present in envelope

excess HBsAg is produced during infection Þ serum aggregations (can be used as diagnosis)

genome:

partially double stranded DNA; circular
complete (-) strand; (+) strand had fixed 5’ with incomplete 3’ of varying length

replication: (-) strand transcribed within the host nucleus Þ (+) RNA which is packaged into the viral capsid

(+) RNA is called ‘pre-genome’
(-) DNA is made from the (+) RNA via reverse transcriptase; (+) RNA degenerates
(+) DNA is synthesized to complement the (-) strand

genes:

S Þ major envelope protein (HBsAg)

C Þ internal core proteins

HBcAg: presence indicates acute phase of the infection; cannot form immune response against this
HBeAg: presence indicates possible serious infection

P Þ virus associated polymerase (has DNA polymerase, reverse transcriptase, RNase functions)

acts as primer for (-) strand synthesis; (+) strand primer is fragmented ‘pre-genome’

X Þ 5’ protein linking to (-) DNA strand; serves regulatory function

transcription activator, but requires cellular transcriptional factors for binding

transmission: major agent in blood transferred hepatitis

reservoir is human chronic carriers

post-transfusion; sexual contact; shared needles, dialysis patients; hospital; mother-newborn

diagnosis:

anti HBcAg during acute phase; anti HBsAg later (could indicate either self-limiting or chronic carrier state)
anti HBcAg is first to develop and persists, but is non-protective
HBeAg, HBsAg develop later and are responsible for removal of the virus

treatment:

IgG for symptoms; vaccine to recombinant HB antigens; or combined therapy

outcomes:

60-70% are subclinical (anicteric); 20-35% icteric disease

90% fully recover; 2-10% (of total infected) have chronic disease Þ widely variable depending on location

chronic disease is most common in central and southern Africa and SE Asia

mortality: 0.2-0.5% based on infection; 0.5-1.5% based on icteric cases

immunization: passive via HBV surface antigens

hepatocellular carcinoma (HCC):

chronic carrier state has 10-30x higher risk

30-40 year latency suggests ‘second-hit’ model; aflotoxins may be second-hit esp in Africa, SE Asia

X gene is potential oncogene: has ability to transactivate c-myc Þ ‘direct model’

not expressed in human HCC, so may just be initiator and not needed for maintence

‘indirect model’: HCC is result of host response to HBV injury (i.e. hepatocyte regeneration Þ mutation)

Hepatitis D

<1% of viral hepatitis; delta agent; replication depends on Hep B to supply the coat protein – causes severe hepatitis with persistent infection

small, enveloped, single stranded RNA

envelope contains HBsAg same as Hep B (must co-infect with Hep B because Hep D cannot make HBsAg)

Delta Ag: unique to Hep D Þ indicates co-infection with Hep B

transmission and treatment same as Hep B

clinical signs: D and B Þ acute symptoms same as with just A or B but more risk of severe infection

superinfection of chronic carriers of B Þ relapse, chronic cirrhosis, progressive liver disease

Hepatitis C

5% of viral hepatitis; causes mild hepatitis with persistent infection

RNA similar to flavivirus

accounts for 75% of post-transfusion hepatitis

transmission through blood, sex, shared needles, etc

acute infection is mild; chronic Þ liver disease

Ig develop slowly in the host making diagnosis difficult

Hepatitis E

<1% of viral hepatitis; calicivirus family; variable symptoms

non-enveloped, spherical, has spikes

RNA

fecal-oral transmission (poor sanitation)

rare in U.S.

lab diagnosis: virus specific IgM

note: study of hepatitis viruses is difficult because it is hard to find cell lines that will propagate the virus in vitro