Human Papillomavirus (HPV)-Associated Neonatal Giant Cell Hepatitis (NGCH)

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Abstract
Neonatal giant cell hepatitis (NGCH) is a clinicopathological syndrome that has been related to perinatal infections and metabolic disorders. In a great number of cases no apparent etiology has been found. To characterize the possible relationship between human papillomavirus (HPV) and idiopathic NGCH (INGCH) we analyzed paraffin-embedded hepatic biopsies from seven cases of INGCH for the presence of both HPV and cytomegalovirus (CMV) DNA. Clinically, jaundice, detected within the first 3 days of life (except in one case), and raised levels of serum transaminases and bilirubin, mainly the direct fraction, were recorded in all. Follow-up of six patients revealed complete recovery. In a "blind" experiment, samples were studied along with appropriate controls [2 cases of CMV hepatitis, one case of postinfantile GCH, 12 cases of juvenile laryngeal papillomatosis (JLP), and 5 normal neonatal liver samples] by polymerase chain reaction (PCR). All DNA samples from INGCH consistently showed positive HPV DNA amplification. This was also found in the samples from postinfantile GCH and JLP. In addition, a second biopsy performed 11 months later in one of the cases of INGCH revealed scattered multinucleated hepatocytes and was still positive for HPV DNA. CMV-DNA was detected only in the cases of CMV hepatitis. All five normal livers were negative for HPV and CMV-DNA. These data seem to indicate that HPV may be closely related to a subset of "idiopathic" NGCH with good outcome.