Maternal hepatitis E virus infection: Immunopathogenesis, genotype-specific severity, and vertical transmission dynamics

Table 1 Genotype-specific characteristics of hepatitis E virus infection in pregnancy

Genotype	Host range	Transmission route	Geographic distribution	Maternal outcomes	Vertical transmission	Key features
HEV-1	Human-restricted	Fecal-oral (waterborne)	Asia (India, Pakistan, Bangladesh, and Nepal)	Fulminant hepatic failure, high mortality (15%-30%)	High (pooled transmission rate is 36.9% with a range from 33%-100%)	High placental tropism, strong cytokine response
HEV-2	Human-restricted	Fecal-oral	Africa, Central America	Similar to HEV-1 (FHF, fetal loss)	Moderate-high (limited evidence)	Less studied, similar epidemiology to HEV-1
HEV-3	Zoonotic	Foodborne (pork, animals)	Europe, North America, Asia East Asia	Usually asymptomatic or mild hepatitis	Not reported	Can cause chronic infection in immunocompromised; transfusion related
HEV-4	Zoonotic	Foodborne		Generally mild disease in pregnancy	Rare	Rare, adverse pregnancy outcome; transfusion related

HEV: Hepatitis E virus; FHF: Fulminant hepatic failure.

Table 2 Maternal, fetal, and neonatal outcomes associated with hepatitis E virus infection during pregnancy

Outcome category	Clinical outcome	Reported risk/findings	Key determinants
Maternal	Fulminant hepatic failure	Leading cause of death	HEV-1 infection, 3rd trimester
	Maternal mortality	15%-30% (endemic regions)	Viral load, delayed care
	Disseminated intravascular coagulation	Common complication of FHF	Hepatic failure + bleeding + hypercoagulability
	Liver dysfunction	ALT > 1000 IU/L, coagulopathy	Cytokine storm, viral replication
Fetal	Intrauterine fetal demise	High frequency	Maternal instability, placental damage
	Stillbirth	Increased risk (OR approximately 2.6)	Severe maternal disease
	Preterm birth	OR approximately 3.4	Placental dysfunction
	Low birth weight	OR approximately 3.2	Maternal illness, inflammation
	IUGR	Increased risk	Placental insufficiency
Neonatal	Vertical transmission	36.9% (range from 33%-100%)	Maternal viral load
	Neonatal mortality	Approximately 8% (median)	Severe maternal disease
	Acute hepatitis	Common	Viral replication
	Coagulopathy	Severe cases	Liver dysfunction
	Prognosis	Self-limited if survives	Viral clearance in weeks-months

HEV: Hepatitis E virus; IUGR: Intrauterine growth restriction; FHF: Fulminant hepatic failure; ALT: Alanine aminotransferase; OR: Odds ratio.

Table 3 Simplified differential diagnosis of hepatitis E virus infection in pregnancy

If the patient has etc.	Most likely diagnosis
Viral prodrome + positive HEV RNA/IgM	HEV infection
Hypertension/proteinuria + thrombocytopenia + hemolysis	HELLP syndrome
Hypoglycemia + hyperammonemia + severe coagulopathy	Acute fatty liver of pregnancy
Severe pruritus + elevated bile acids	Intrahepatic cholestasis of pregnancy

HEV: Hepatitis E virus; IgM: Immunoglobulin M; HELLP: Hemolysis, elevated liver enzymes and low platelets count.