Acute Hepatitis E

Acute hepatitis E is liver infection caused by hepatitis E virus (HEV), a non-enveloped RNA hepevirus.

• Genotypes 1 and 2 spread by faecal contaminated water in outbreaks in Africa and Asia (including refugee camps and flooding in Kenya, Uganda and South Sudan); genotypes 3 and 4 are zoonotic (pork, wild boar, deer), and cause sporadic disease and chronic infection.
• Incubation is 2 to 8 weeks (average 40 days).
• Pregnant women, especially in the third trimester, have mortality up to 20 to 25 percent.

Most are asymptomatic or mildly ill; symptomatic disease shows malaise, anorexia, nausea, abdominal pain, fever, jaundice, dark urine, pruritus and hepatomegaly.

• Pregnancy: fulminant hepatitis, coagulopathy, preterm labour, stillbirth, postpartum haemorrhage.
• Differential diagnosis: hepatitis A, B, C and D, leptospirosis, malaria, typhoid, yellow fever, Rift Valley fever, Epstein-Barr virus, cytomegalovirus, drug-induced liver injury, autoimmune hepatitis.
• Complications: acute liver failure (0.5 to 3 percent; higher in pregnancy and chronic liver disease), cholestatic hepatitis, chronic infection with cirrhosis (genotype 3 in solid organ transplant recipients, haematological malignancy and HIV with low CD4), neurological syndromes (Guillain-Barre syndrome, neuralgic amyotrophy), glomerulonephritis, pancreatitis, haemolysis in G6PD deficiency.

Anti-HEV IgM and HEV RNA by PCR in serum and stool; anti-HEV IgG indicates past exposure.

• Immunosuppressed patients: HEV RNA (antibody tests are unreliable); persistence beyond 3 months defines chronic infection.
• ALT frequently 1000 to 3000 IU/L, bilirubin, INR, albumin, glucose, creatinine.
• Exclude other causes: hepatitis A IgM, HBsAg and IgM anti-HBc, anti-HCV, malaria film, HIV.

Supportive

• Hydration, nutrition, rest, no alcohol, avoid hepatotoxic drugs, paracetamol up to 2 g daily.
• Admit pregnant women, patients with INR above 1.5, encephalopathy, dehydration or comorbidity.
• Pregnancy: monitor mother and fetus, treat coagulopathy (vitamin K 10 mg IV, fresh frozen plasma), delivery by obstetric indications, intensive care for liver failure.

Pharmacological

• Acute infection in an immunocompetent patient needs no antiviral.
• Severe disease or acute-on-chronic liver failure: ribavirin 600 to 1000 mg daily (about 15 mg/kg/day) for 3 weeks has been used; avoid in pregnancy (teratogenic).
• Chronic HEV in immunosuppressed patients: first reduce immunosuppression (for example, lowering the tacrolimus dose); if viraemia persists after 3 months, ribavirin 600 to 1000 mg daily for 3 months (extend to 6 months if relapse), with haemoglobin monitoring and dose reduction for anaemia.
• Acute liver failure: N-acetylcysteine (150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours), lactulose 30 mL every 6 to 8 hours, mannitol 0.5 g/kg for cerebral oedema, urgent transplant referral.

Prevention: safe water (chlorination, boiling), sanitation and handwashing; cook pork and game thoroughly; HEV vaccine is available in China but not widely elsewhere.

Special groups: pregnant women (high mortality), people with chronic liver disease, transplant recipients and HIV (chronic infection).

Red flags: encephalopathy, INR above 1.5, hypoglycaemia, ascites, third trimester pregnancy, oliguria.

Follow-up: ALT and HEV RNA weekly while acute then at 3 months; confirm viral clearance in immunosuppressed patients.