Cytomegalovirus and Human Herpesvirus 6, but Not Human Papillomavirus, Are Present in Neonatal Giant Cell Hepatitis and Extrahepatic Biliary Atresia

Abstract

The purpose of our study was to confirm reports of an association of human papillomavirus (HPV) with neonatal giant cell hepatitis (GCH) and biliary atresia (BA), and to expand these studies to include cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19). Frozen hepatic tissue was available for polymerase chain reaction (PCR) analysis in 19 cases of GCH or BA and 8 controls. Nested PCR to detect HPV types 6, 16, 18, and 33 was followed by 32P hybridization with generic probes. PCR followed by hybridization with a digoxigenin-labeled probe was used for all other viruses. HPV, EBV, and PVB19 were not detected in cases or controls. Two cases of GCH and 1 case of BA were PCR positive for CMV; controls were negative. HHV6 was detected in 6 cases: 2 GCH, 2 BA, and 2 controls. We conclude that HPV is not associated with GCH or BA. Detection of CMV in BA and GCH confirms other reports of this association. HHV6 requires further study to determine the significance of a positive PCR test in the livers of infants.

Unraveling the Pathogenesis and Etiology of Biliary Atresia

“…However, a Canadian group (30) could not demonstrate CMV in bile duct remnants from 12 children with BA. Finally, other viruses have also been examined including papillomavirus (31,32) and herpes virus-6 (32) with similar conflicting results.…”

Cholangiocyte expression of α2β1-integrin confers susceptibility to rotavirus-induced experimental biliary atresia

“…It is the most common indication for pediatric liver transplantation (24). Because pathogenic viruses have been found in the livers of children afflicted with biliary atresia (10,12,18,26,29), a proposed etiology for biliary atresia is perinatal infection by a virus triggering inflammatory destruction of the biliary epithelium (3,23,32). A murine model of biliary atresia (30) supports a viral pathogenesis where newborn mice infected with rhesus rotavirus (RRV) develop inflammation within the portal tract (31) and extrahepatic bile duct obstruction (9, 27).…”

Effect of Rotavirus Strain on the Murine Model of Biliary Atresia

“…Two types of evidence support a viral role in the pathogenesis of biliary atresia. The first type is patient-based studies in which viruses, including reovirus (11,19,20), cytomegalovirus (7,9), human papillomavirus (8), Epstein-Barr virus (10), and rotavirus (27), were found in the livers of infants with biliary atresia. The second type of evidence is the murine model of inflammatory cholangiopathy in which newborn mice injected with rhesus rotavirus (RRV) develop extrahepatic biliary obstruction and death (28).…”