What is the diagnosis and treatment for a pregnant woman or individual with pre-existing liver disease suspected of having Hepatitis E (HEV)?

Hepatitis E: Diagnosis and Management

Critical High-Risk Populations Requiring Immediate Recognition

Pregnant women with Hepatitis E, particularly those infected with genotype 1 or 2, face a mortality rate of approximately 25% and must be managed in a high-dependency setting with immediate transfer to a liver transplant unit if liver failure develops. 1

Pregnancy-Specific Considerations

• Mortality risk is highest in the second and third trimesters, with deaths caused by fulminant hepatic failure and obstetric complications including eclampsia and hemorrhage 1
• Fetal and neonatal mortality is severe: median fetal case fatality rate of 33% (IQR 19-37%) and neonatal case fatality rate of 8% (IQR 3-20%) 1
• HEV is responsible for approximately 3,000 stillbirths worldwide annually 1
• Vertical transmission occurs in 36.9% of cases when maternal HEV RNA is detectable, with risk significantly increased when maternal viral load exceeds 13,266 copies/ml 1
• Delivery of the fetus (preterm birth or therapeutic termination) can be considered to reduce maternal morbidity and mortality in mothers with acute severe hepatitis E and encephalopathy grade I-III 1
• Vaginal delivery should not be discouraged in women with HEV infection 1
• Breastfeeding should not be discouraged in HEV-infected asymptomatic mothers 1

Patients with Pre-Existing Liver Disease

• 12-month mortality rate approaches 70% in patients with underlying chronic liver disease who develop HEV superinfection 1
• Mortality rates vary widely (0-67%) depending on the study and genotype, with HEV genotype 1 infections showing higher mortality in Asian studies 1
• HEV most commonly complicates patients with Wilson's disease among those with chronic liver disease 1
• Recent data suggest HEV-associated acute-on-chronic liver failure may have a more benign course than alcohol-associated cases 1

Diagnostic Approach

Serological Testing

• Test for IgM anti-HEV antibodies to diagnose acute infection 2
• Confirm positive IgM results with HEV RNA testing, particularly in low-endemicity areas, as current IgM assays have high interassay discordance 2
• IgG anti-HEV indicates exposure (recent or remote) but has low concordance between assays 2

Molecular Testing

• HEV RNA detection is the gold standard for confirming active infection 2
• Essential for confirming diagnosis in pregnant women and immunocompromised patients 2

Clinical Assessment

• Monitor for signs of acute liver failure: coagulopathy (INR ≥1.5), mental status changes, rising bilirubin 3
• Obtain comprehensive laboratory evaluation: liver enzymes, prothrombin time/INR, complete blood count, comprehensive metabolic panel 3
• Travellers with hepatitis returning from areas endemic for HEV genotype 1 or 2 should be tested for HEV 1

Treatment Strategies

Pregnant Women

• Ribavirin is contraindicated in pregnancy due to teratogenicity, and there are currently no data to support its use in pregnant patients with HEV 1
• Management consists of high-dependency supportive care with close monitoring for fulminant hepatic failure 1
• Transfer to liver transplant unit immediately if liver failure develops 1
• Consider expedited delivery if acute severe hepatitis with encephalopathy grade I-III develops 1

Patients with Pre-Existing Liver Disease

• Ribavirin monotherapy should be considered for patients with severe infection, fulminant hepatic failure, or acute-on-chronic liver failure to expedite viral clearance 4
• Standard supportive care remains the foundation of treatment 5
• Active monitoring for complications of liver failure 5
• Liver transplantation is the definitive treatment for liver failure in patients who do not improve with supportive measures 5

Immunocompetent Patients

• Acute HEV genotype 1 and 2 infections are typically self-limiting and require only supportive care 1
• Avoid all hepatotoxic medications, particularly acetaminophen, and complete alcohol abstinence 3
• Monitor hepatic panels (ALT, AST, bilirubin, INR) every 2-4 weeks until resolution 3

Immunocompromised Patients (Chronic HEV)

• Reduce immunosuppressive therapy, especially T-cell targeting agents, as this achieves viral clearance in approximately one-third of cases 4
• If immunosuppression cannot be reduced or viral clearance does not occur, initiate ribavirin monotherapy for 12 weeks 4
• Pegylated interferon for 3-12 months clears virus in liver transplant recipients and hemodialysis patients 4
• In kidney and heart transplant patients where interferon may cause organ rejection, use ribavirin alone 4

Genotype-Specific Epidemiology

Genotypes 1 and 2 (Endemic Areas)

• Obligate human pathogens spread via fecal-oral route through contaminated water 1
• Cause disease in areas with fragile sanitary infrastructure in Asia (gt 1), Africa (gt 1 and 2), and Mexico (gt 2) 1
• Chronic infection with genotypes 1 and 2 has not been reported 1

Genotypes 3 and 4 (Developed Countries)

• Zoonotic transmission, primarily from pigs, wild boar, and deer 1
• At least two million locally acquired HEV infections occur in Europe annually 1
• Transmission through undercooked pork products or direct animal contact 1

Critical Pitfalls to Avoid

• Do not delay transfer to high-dependency unit or transplant center for pregnant women with HEV showing signs of liver failure 1
• Do not use ribavirin in pregnant women despite its efficacy in other populations 1
• Do not assume HEV is self-limiting in patients with pre-existing liver disease or pregnancy 1
• Do not rely solely on IgM anti-HEV without RNA confirmation, especially in low-endemicity areas 2
• Do not fail to reduce immunosuppression in transplant recipients with chronic HEV before initiating antiviral therapy 4