Hepatitis E

Question 1

How many genotypes of HEV are there? Which infect humans?

Answer 1

8 genotypes

HEV-1 - human only (Africa and Asia)

HEV-2 - human only (Africa and Mexico)

HEV-3 (mostly Europe) and 4 (mostly Asia) - worldwide distribution, infect humans and pigs/wild boar/deer/rabbits

HEV-5/6 - wild boar only

HEV-7/8 - camels (sporadic infection in human)

Question 2

Diagnosis of hepatitis E and length of detection of virus

Answer 2

From week 3-6 week = viraemia
From week 4-6 week = virus in stool

IgM plus ‘rising’ IgG tire or RNA pos

PCR always for immunocompromised as serology unreliable

Question 3

Clinical spectrum of HEV in immunocompetent

Answer 3

95% asymptotic

Symptoms = jaundice, acute hepatitis, raised liver enzymes, fatigue, itching, nausea

Acute liver failure rare in GT3

HEV1/2 can be more severe and lead to ALF especially in pregnancy, elderly and those with chronic liver disease

Question 4

Clinical symptoms of severe HEV infection

Answer 4

ALF or fulminant liver failure

Loss of consciousness
Persistent vomiting
Haemorrhages
Mental state changes
Increased intracranial pressure
Respiratory issues
Coagulopathy
Ascites

Question 5

Differential diagnosis of acute HEV

Answer 5

Drug induced liver injury
Autoimmune hepatitis
Hepatitis A/B/C, EBV/CMV

Yellow fever/dengue/malaria

Question 6

Differential diagnosis of chronic HEV

Answer 6

Graft rejection
Drug induced liver injury
GVHD
EBV/CMV reactivation

Question 7

Extrahepatic manifestations of HEV

Answer 7

1. Neurological (brachial neuritis, GBS, encephalitis/myelitis, myositis, peripheral neuropathy, Bell’s palsy, vestibular neuritis, mononeuritis multiplex)
2. Renal (glomerulonephritis)
3. Pancreatitis
4. Haematological (thrombocytopenia, cryoglobulinaemia, aplastic anaemia, haemolytic anaemia)

Question 8

What additional testing is required when HEV detected in pregnancy and why?

Answer 8

Genotyping required, esp if travelled (as per SMI)

HEV1/2 have 25% mortality rate in pregnancy due to fulminant liver failure and obstetric complications such as pre eclampsia and haemorrhage

Particular risk in third trimester

Transmission can occur from mother to baby

Question 9

Which genotypes cause chronic hepatitis E and what is the definition of chronic HEV?

Answer 9

HEV-3/4

Definition of RNA detection for 6 months (however little spontaneous clearance after 3 months so 3 months used in UK)

Question 10

What is the clearance rate of SOT patients with HEV?

Answer 10

1/3 will clear

2/3 will become chronic

Question 11

What is the progression of liver disease in chronic HEV?

Name two risk factors in SOT for chronic HEV

Answer 11

Fibrosis > cirrhosis > decompensated disease > death

Interestingly fibrosis can regress after viral clearance

1. Low lymphocyte count 2. Tacrolimus

Question 12

Treatment for acute HEV

Answer 12

None - supportive

In acute liver failure treat with ribavirin +/- corticosteroids (no data to support either!)

Question 13

Treatment of chronic HEV in SOT and non-SOT

Answer 13

SOT

1. Reduction of immunosuppression (particularly T cell suppressants) this resolves 1/3 cases
2. Ribavirin - for 3 months, if no clearance continue for 6 months
3. IN LIVER TX ONLY 3 month course of PEG-IFN

Non-SOT

No reduction of immunosuppression due to risk of rejection

1. Ribavirin +/- PEG-IFN

Sofosbuvir has been used in case reports but trail data does not sure clearance

Question 14

Monitoring in chronic HEV

Answer 14

Monthly screening in blood +/- stool

Two consecutive monthly negatives in both plasma and stool - recheck for rebound at 6 months (treated or not)

Quantitative PCR recommended. Viral load at day 7 is indicative of SVR

Treatment can be stopped when stool and plasma are negative twice, one month apart

Test for SVR at 3 and 6 months after EOT