Hepatitis E

Question 1

HEV family and structure

Answer 1

Family: Hepeviridae
Genus: Orthohepevirus
Species A to D
Strains 1 & 2 in species A - human disease
C1 - Rat Hepe virus with human cases

Of these, 8 genotypes - 1&2 exclusively humans, 3&4 zoonotic,
5&6 only wild boar, 7 in humans from camel meat/milk, 8 only in Camels

(+) SS RNA NON enveloped

BALTIMORE 4

ORF1 - codes for methyl transferase, RNA helicase, RNA-dependent RNA polymerase
ORF2 - capsid
ORF3 - viral particle release protein

Question 2

HEV serotypes 1&2 mortality

Answer 2

Mortality - 25% in pregnancy, 70% in CLD

Question 3

HEPE genotype 3 & 4 clinical syndromes

Answer 3

Symptomatic in 5%
No excess mortality in pregnancy
ALF and hepatitis

Chronic in immunosuppressed (>6 months persistence)
Majority asymptomatic
Transaminitis
CLD and fibrosis
EASL recommends HEV testing in immunosuppressed with transaminitis

Extrahepatic:
1. Neuro - Neuralgic amyotrophy, GBS, encephalitis
2. Gomerulonephritis
3. Cryoglobulunaemia
4. Pancreatitis
5. Severe thrombocytopenia
6. Myocarditis

Question 4

HEPE incubation

Answer 4

SEE ALBUM

15 to 60 days
RNA detectable just before symptom onset to 4-6 weeks post
IgM short lived but IgG long lasting with increasing avidity

Question 5

HEPE diagnostics

Answer 5

SEE ALBUM

PCR - targeting ORF2
Serology, antigen, IHC

Persisting RNA > 3 months - persistent HEV

Question 6

HEPE treatment

Answer 6

Acute - Nil

Severe acute - consider ribavirin

Chronic - Ribavirin mono therapy 600mg/day for 3 months - 80% SVR

If persistent positive at 3 months, complete 6 months of treatment.

Mechanism not entirely clear - depletion of GTP pools

G1634R mutation - Ribavirin failure

Sofosbuvir under trial

PEG INF alpha for 3 months in liver transplant patients.

Question 7

HEPE vaccine

Answer 7

Recombinant vaccine (Hecolin) encompassing ORF2

Licenced only in China in 2011
97% efficacy

Question 8

HEV SMI

Answer 8

SEE ALBUM

Question 9

HEV extra hepatic manifestations

Answer 9

1. Neuro:
   A. Amyotrophy
   B. GBS
   C. Meningitis
   D. Encephalitis
   E. Bell’s
   F. Vestibular neuritis
2. Renal:
   A. Membranous GN
   B. IgA nephropathy
3. Haem
   A. Thrombocytopenia
   B. Cryoglobulinemia
   C. Aplastic anemia
   D. Haemolytic anaemia
4. Other
   A. Acute pancreatitis
   B. Arthritis
   C. Myocarditis
   D. Autoimmune thyroiditis