HSV-1 and Fetal Hepatic Calcification
No, HSV-1 is not a recognized cause of fetal hepatic calcification. The available evidence consistently identifies cytomegalovirus (CMV) as the primary viral etiology associated with fetal liver calcifications, not herpes simplex virus.
Evidence from Congenital Infection Guidelines
The CDC/NIH guidelines specifically state that hepatic calcifications on fetal ultrasound indicate the possibility of in utero CMV infection, not HSV infection 1. When ultrasound reveals cerebral calcifications, abdominal and liver calcifications, hydrops, microcephaly, ventriculomegaly, ascites, or echogenic fetal bowel in pregnant women with CMV end-organ disease, these findings warrant consideration of invasive testing such as amniocentesis 1.
Research Evidence on Fetal Hepatic Calcifications
Multiple large prenatal series examining fetal liver calcifications have systematically excluded HSV as a causative agent:
In a series of 14 fetuses with hepatic calcifications, no case had serologic evidence of recent HSV infection 2. The study specifically tested for Toxoplasma, rubella, CMV, HSV, and syphilis, with all HSV testing negative.
A larger cohort of 61 fetuses with liver calcifications found only two cases of intrauterine infection: one CMV and one parvovirus B19 3. HSV was not identified as a cause despite comprehensive STORCH screening that included HSV-1 and HSV-2 testing.
Isolated fetal liver calcifications with no aneuploidy and no infection have a good prognosis 4, and HSV is not mentioned among the infectious etiologies to exclude.
HSV Hepatitis in Pregnancy: A Maternal Disease
While HSV can cause severe hepatitis in pregnant women, this manifests as maternal disease, not fetal hepatic calcification:
HSV hepatitis in pregnancy presents as acute maternal liver injury with transaminitis, not fetal calcifications 5. A case report of gestational HSV-1 hepatitis at 38 weeks showed maternal liver injury, but there was no evidence of neonatal seroconversion or fetal liver involvement 5.
Disseminated HSV infection during pregnancy primarily causes maternal hepatitis and encephalitis 6. Even in fatal maternal cases with HSV demonstrated in the maternal liver, the focus is on maternal disease rather than fetal hepatic calcification 6.
The CDC guidelines describe HSV hepatitis as a nonmucosal HSV infection in adults 1, not as a cause of congenital fetal abnormalities like hepatic calcifications.
Clinical Algorithm for Fetal Hepatic Calcifications
When fetal hepatic calcifications are identified on ultrasound:
Perform detailed fetal ultrasound for associated abnormalities (particularly looking for findings suggestive of CMV: cerebral calcifications, ventriculomegaly, microcephaly, hydrops, ascites) 1, 3
Obtain maternal STORCH serology focusing on CMV, not HSV 2, 3. CMV is the viral pathogen of concern for fetal hepatic calcifications.
Offer amniocentesis for karyotype and CMV PCR/culture 1, 3, as chromosomal abnormalities (particularly trisomy 13) and CMV are the primary concerns.
If isolated calcifications with negative workup, prognosis is excellent 4, 2, 3. No HSV testing is routinely indicated for isolated fetal liver calcifications.
Important Caveat
Do not confuse maternal HSV hepatitis with fetal hepatic calcification. While pregnancy is a risk factor for severe maternal HSV hepatitis with high morbidity and mortality 5, 6, this does not translate to fetal liver calcifications. The pathophysiology, timing, and clinical manifestations are entirely different. Maternal HSV hepatitis requires prompt serum PCR screening and acyclovir treatment 5, but fetal hepatic calcifications warrant CMV investigation, not HSV testing 1, 2, 3.