Hepatitis E: Discovery, global impact, control and cure

Table 1 Hepatitis E: Global epidemiology and clinical profile

	Developing countries		Developed countries
Genotypes	HEV-1	HEV-2	HEV-3	HEV-4
Distribution	Asia, Africa, Latin America	Mexico, West Africa	Worldwide	China, East Asia, Central Europe
Disease pattern	Epidemic, Endemic		Autochthonous, sporadic, case-clusters
Attack rate	About 1 in 2		67%-98% asymptomatic
Seasonality	Yes		No
Reservoir	Human		Animals (pig, boar, deer)
Transmission	Water, person-to-person, vertical		Zoonotic-food-borne, vocational, infected water
Transfusion-associated	Reported		Yes (well-studied)
Seroprevalence	Low (< 15 yr), rapid increase		Steady increase throughout age groups; varies 7% to 21%
	(15-30 yr), plateau at 30%-40%
Seroincidence	64/1000-yr		30 (South France), 2 (United Kingdom)
			7 (United States)/1000-yr
Age (yr)	15-40		> 50
Sex	2:1		> 3:1
Clinical outcome	Self-limiting in most		Self-limiting in most
Risk factors	Pregnancy, Cirrhosis		Cirrhosis, LTx, HIV
Deaths in pregnancy	High (25%)		Not reported
HEV superinfections	Common, poor outcome		Reported, poor outcome
Extra-hepatic disease	Yes		Yes
Chronic infection	Not reported		HEV-3; SOT, HIV, hem NP
Burden	3.4 million cases/yr, 70000 deaths, 3000 still births		Unknown

Adopted from Khuroo et al[143] 2016. HEV: Hepatitis E virus; HIV: Human immunodeficiency virus.

Table 2 Diagnosis of hepatitis E virus infection

Test	Method	Uses	Comments
IgM anti-HEV	ELISA	Acute infection	Assays vary in performance, issue of genotype applicability, poor performance in immune disorders, cross-reactive with other viral infections
	ICT (POCT)
IgG anti-HEV	ELISA	Seroprevalence	Assays vary in performance
	ICT (POCT)	Acute infection
		Natural protection
		Vaccine efficacy
HEV RNA	NAT	Acute infection	Viremia short-lasting, in-house assays vary in performance, advantage immune disorders
		Confirm chronicity
		Anti-viral response
		Donor screening
HEV antigen	EIA	Acute infection	81% concordance with HEV RNA

Adopted from Khuroo et al[143], 2016. HEV: Hepatitis E virus; ICT: Immunochromatographic test; POCT: Point of care test; NAT: Nucleic acid test; EIA: Enzyme immunoassay.

Table 3 Effect of drugs on hepatitis E virus replication and their use and impact on immunosuppressant therapy during chronic hepatitis E virus infection in solid organ transplant patients

Class	Drug	Effect on HEV replication	Clinical use
Calcineurin inhibitors	Cyclosporine, tacrolimus	Stimulates HEV replication with increase in HEV load and promotes HEV persistence	Reduce dose
mTOR inhibitors	Rapamycin, everolimus	Stimulates HEV replication with increase in HEV load	Reduce dose
Antimetabolite immunosuppressant	Mycophenolate mofetil	Inhibits HEV replication and helps HEV clearance	Continue the drug
Guanosine analog	Ribavirin	Inhibits HEV replication and causes HEV clearance	Primary drug for therapy
Cytokines	Pegylated interferon α	Inhibits HEV replication and causes HEV clearance	Indicated if Ribavirin therapy fails
Nucleotide analog	Sofosbuvir	Inhibits HEV replication in vitro	Unclear, clinical trials indicated

HEV: Hepatitis E virus.