A 32-year-old woman presented in week 31 of her pregnancy with a 7-day history of nausea, intermittent vomiting, and fever. Investigations revealed significantly abnormal liver function (bilirubin: 45 μmol/L [normal: <18 μmol/L]; alkaline phosphatase: 211 U/L; alanine aminotransferase (ALT) = 2360 U/L; gamma-glutamyl transferase: 74 U/L; international normalized ratio: 1.6). The provisional diagnosis was fatty liver of pregnancy.
Despite emergency caesarian section, the patient's condition deteriorated and intubation was required on day 2 for hepatic encephalopathy. Computed tomography scan of the abdomen demonstrated patent hepatic vessels and an enlarged liver with parenchymal changes suggestive of fatty infiltration. Hepatitis A/B/C serology returned negative, and because of the diagnostic uncertainty at that point, both intravenous acyclovir and N-acetyl-cysteine were commenced. On postpartum day 3, the patient underwent urgent transplantation for acute liver failure. A diagnosis of fulminant liver failure from herpes simplex virus (HSV) was confirmed following pathological examination of the explanted liver.
Figure 1 is a section of explanted liver. The liver is enlarged and congested. The yellow mottled areas correspond to the only residual viable parenchyma. In Figure 2, extensive geographic pauci-inflammatory, hemorrhagic necrosis is demonstrated. Figure 3, a high-power section, demonstrates multinucleated cells with ground-glass intranuclear inclusions (arrow) and peripheral chromatin condensation characteristic of HSV hepatitis. Figure 4 demonstrates nuclear staining of affected hepatocytes with HSV-2.
The patient was treated with intravenous acyclovir and will remain on lifelong valganciclovir. Her infant was diagnosed with disseminated HSV on day 9. He has survived but long-term sequelae are not yet known.
HSV hepatitis is an extremely rare disease with an associated mortality of 74%.1 Between 1960 and 2007, only 32 cases during pregnancy were reported with more than 50% diagnosed at postmortem examination.1 The restricted T cell function that occurs in the third trimester in order to prevent rejection of the fetus is thought to allow the development of systemic HSV infection.2 Features suggestive of HSV hepatitis are an absence of jaundice and a marked elevation of aspartate aminotransferase (AST) and ALT with very high AST/ALT ratios. There may be right upper quadrant pain and fever. Genital or oral herpetic lesions are reported in only half the cases.3
No controlled trials exist for antiviral therapy in HSV hepatitis. However, retrospective data supports antiviral use. A 37% reduction (P = 0.03) in transplant/death was found with the use of acyclovir in a 2007 review.1
In the neonate, disseminated HSV infection has a mortality of 29% and is associated with significant long-term sequelae, including learning disabilities, cerebral palsy, blindness, and persistent seizures.4
HSV hepatitis is a rare but important diagnosis to consider in any pregnant woman presenting with fulminant hepatic failure of uncertain etiology. Empiric treatment with acyclovir should be considered in this clinical context. In addition, this case highlights the importance of close liaison with the neonatologists and consideration of empiric acyclovir in the newborn.