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Chapter 10 - Neonatal Hepatitis and Congenital Infections

from Section II - Cholestatic Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Philip Rosenthal  and
Leina Alrabadi
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
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Summary

Neonatal hepatitis refers to a heterogeneous group of disorders that result in a somewhat similar morphologic change in the liver of an infant younger than three months of age in response to various insults. The term neonatal hepatitis has been used at times to include all causes of cholestasis in infancy in which extrahepatic biliary obstruction is excluded. Although in the majority of cases an etiology cannot be found, specific infectious and metabolic causes have been identified that may present as neonatal hepatitis. At final diagnosis, neonatal hepatitis is responsible for approximately 40% of the cases of infants with cholestasis and is the most frequently encountered liver disorder of early infancy. Males usually predominate over females (2:1). Additionally, some familial cases have been reported, suggesting either a maternal environmental factor or autosomal recessive inheritance.

Type
Chapter
Information
Liver Disease in Children , pp. 147 - 161
Publisher: Cambridge University Press
Print publication year: 2021

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References

Hamilton, JR, Sass-Kortsak, A. Jaundice associated with severe bacterial infection in young infants. J Pediatr 1963;63:121–32.Google Scholar
Zimmerman, HJ, Fang, M, Utili, R, et al. Jaundice due to bacterial infection. Gastroenterology 1979;77:362–74.CrossRefGoogle Scholar
Andres, JM, Walker, WA. Effect of Escherichia coli endotoxin on the developing rat liver. I. Giant cell induction and disruption in protein metabolism. Pediatr Res 1979;13:1290–3.Google Scholar
Bolder, U, Ton-Nu, HT, Schteingart, CD, et al. Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. Gastroenterology 1997;112:214–25.Google Scholar
Borges, MAG, DeBrito, T, Borges, JMG. Hepatic manifestations in bacterial infections of infants and children. Clinical features, biochemical data and morphologic hepatic changes. Acta Hepatogastroenterol 1972;19:328–44.Google Scholar
Lam, HS, Li, AM, Chu, WCW, et al. Mal-positioned umbilical venous catheter causing liver abscess in a preterm infant. Biol Neonate 2005;88:54–6.Google Scholar
Garcia, FJ, Nager, AL. Jaundice as an early diagnostic sign of urinary tract infection in infancy. Pediatrics 2002;109:846–51.Google Scholar
Hoarau, C, Ranivoharimina, V, Chavet- Queru, MS, et al. Congenital syphilis: update and perspectives. Sante 1999;9:38–45.Google Scholar
Herman, TE. Extensive hepatic calcification secondary to fulminant neonatal syphilitic hepatitis. Pediatr Radiol 1995;25:120–2.CrossRefGoogle ScholarPubMed
Kumar, R, Gupta, N, Sabharwal, A. Congenital tuberculosis. Indian J Pediatr 2005;72:631–3.CrossRefGoogle ScholarPubMed
Montoya, JG, Rosso, F. Diagnosis and management of toxoplasmosis. Clin Perinatol 2005;32:705–26.Google Scholar
Desmonts, G, Couvreur, J. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N Engl J Med 1974;290:1110–16.CrossRefGoogle ScholarPubMed
Schmidt, DR, Hogh, B, Andersen, O, et al. Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine. Eur J Pediatr 2005;165:19–25.Google Scholar
Nicol, KK, Geisinger, KR. Congenital toxoplasmosis: diagnosis by exfoliative cytology. Diagn Cytopathol 1998;18:357–61.Google Scholar
Bellomo-Brandao, MA, Andrade, PD, Costa, SC, et al. Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR. World J Gastroenterol 2009;15:3411–16.Google Scholar
Laifer, SA, Ehrlich, GD, Huff, DS, et al. Congenital cytomegalovirus infection in offspring of liver transplant recipients. Clin Infect Dis 1995;20:52–5.CrossRefGoogle ScholarPubMed
Zuppan, CW, Bui, HD, Grill, BG. Diffuse hepatic fibrosis in congenital cytomegalovirus infection. J Pediatr Gastroenterol Nutr 1986;5:489–91.Google Scholar
Watkins, JB, Sunaryo, FP, Berezin, SH. Hepatic manifestations of congenital and perinatal disease. Clin Perinatol 1981;8:467–80.Google Scholar
Weller, TH, Hanshaw, JB. Virologic and clinical observations on cytomegalic inclusion disease. N Engl J Med 1962;266:1233–44.Google Scholar
Snover, DC, Horwitz, CA. Liver disease in cytomegalovirus mononucleosis: a light microscopical and immunoperoxidase study of six cases. Hepatology 1984;3: 408–12.Google Scholar
Greenfield, C, Sinickas, V, Harrison, LC. Detection of cytomegalovirus by the polymerase chain reaction. A simple, rapid and sensitive non-radioactive method. Med J Aust 1991;154:383–5.Google ScholarPubMed
Berenberg, W, Nankervis, G. Long-term follow-up of cytomegalic inclusion disease of infancy. Pediatrics 1970;46:403–10.CrossRefGoogle ScholarPubMed
Dressler, S, Linder, D. Noncirrhotic portal fibrosis following neonatal cytomegalic inclusion disease. J Pediatr 1978;93:887–8.Google Scholar
Thompson, C, Whitley, R. Neonatal herpes simplex virus infections: where are we now? World J Gastroenterol 2009;15:3411–16.Google Scholar
Twagira, M, Hadzic, N, Smith, M, et al. Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by HSV DNA detection in blood and successfully managed by liver transplantation. Eur J Pediatr 2004;163:166–9.Google Scholar
Nakamura, Y, Yamamoto, S, Tanaka, S, et al. Herpes simplex viral infection in human neonates: an immunohistochemical and electron microscopic study. Human Pathol 1985;16:1091–7.Google Scholar
Raga, J, Chrystal, V, Coovadia, HM. Usefulness of clinical features and liver biopsy in diagnosis of disseminated herpes simplex infection. Arch Dis Child 1984;59:820–4.Google Scholar
Egawa, H, Inomata, Y, Nakayama, S, et al. Fulminant hepatic failure secondary to herpes simplex virus infection in a neonate: a case report of successful treatment with liver transplantation and perioperative acyclovir. Liver Transplant Surg 1998;4:513–15.Google Scholar
Schluter, WW, Reef, SE, Redd, SC, et al. Changing epidemiology of congenital rubella syndrome in the United States. J Infect Dis 1998;178:636–41.Google Scholar
Monif, GRG, Asofsky, R, Sever, JL. Hepatic dysfunction in the congenital rubella syndrome. BMJ 1966;1:1086–8.Google Scholar
Strauss, L, Bernstein, J. Neonatal hepatitis in congenital rubella. Arch Pathol 1968;86:317–27.Google ScholarPubMed
Duff, P. Hepatitis in pregnancy. Semin Perinatol 1998;22:277–83.CrossRefGoogle ScholarPubMed
Noble, RC, Kane, MA, Reeves, SA, et al. Posttransfusion hepatitis A in a neonatal intensive care unit. JAMA 1984;252:2711–15.Google Scholar
Renge, RL, Dani, VS, Chitambar, SD, Arankalle, VA. Vertical transmission of hepatitis A. Indian J Pediatr 2002;69:535–6.Google Scholar
Leikin, E, Lysikiewicz, A, Garry, D, Tejani, N. Intrauterine transmission of hepatitis A virus. Obstet Gynecol 1996;88:690–1.Google Scholar
Poland, GA, Jacobson, RM. Prevention of hepatitis B with the hepatitis B vaccine. N Eng J Med 2004;351:2832–8.Google Scholar
Tang, JR, Hsu, HY, Lin, HH, et al. Hepatitis B surface antigenemia at birth: a long-term follow-up study. J Pediatr 1998;133:374–7.Google Scholar
Suskind, DL, Rosenthal, P. Chronic viral hepatitis. Adolesc Med Clin 2004;15:145–58.Google Scholar
Granovsky, MO, Minkoff, HL, Tess, BH, et al. Hepatitis C virus infection in the mothers and infants cohort study. Pediatrics 1998;102:355–9.Google Scholar
Kumar, RM, Shahul, S. Role of breast-feeding in transmission of hepatitis C virus to infants of HCV-infected mothers. J Hepatol 1998;29:191–7.Google Scholar
Chang, MH. Chronic hepatitis virus infection in children. J Gastroenterol Hepatol 1998;13:541–8.CrossRefGoogle ScholarPubMed
Realdi, G, Alberti, A, Rugge, M, et al. Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis. Gut 1982;23:270–5.Google Scholar
Hasan, F, Jeffers, LJ, De Medina, M, et al. Hepatitis-C associated hepatocellular carcinoma. Hepatology 1990;12:589–91.Google Scholar
McHutchison, JG, Gordon, SC, Schiff, ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998;339:1485–92.Google Scholar
Fried, MW, Shiffman, ML, Reddy, KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–82.Google Scholar
Gonzalez-Peralta, RP. Treatment of chronic hepatitis C in children. Pediatr Transplant 2004;8:639–43.Google Scholar
Bortolotti, F, Iorio, R, Nebbia, G, et al. Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders. Dig Liver Dis 2005;37:336–41.Google Scholar
Schwarz, KB, Gonzalez-Peralta, RP, Murray, KF, et al. The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. Gastroenterology 2011;140:450–8.Google Scholar
Terrault, NA, Lok, ASF, McMahon, BJ, chang, KM, Hwang, JP, Jonas, MM, Brown, RS Jr., et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560–99.CrossRefGoogle ScholarPubMed
Chen, HL, Chang, MH, Lin, HH, et al. Antibodies to E2 protein of hepatitis G virus in children: different responses according to age at infection. J Pediatr 1998;133:382–5.CrossRefGoogle ScholarPubMed
Zanetti, AR, Tanzi, E, Romano, L, et al. Multicenter trial on mother-to-infant transmission of GBV-C virus. The Lombardy Study Group on Vertical/Perinatal Hepatitis Viruses Transmission. J Med Virol 1998;54:107–12.Google Scholar
Woelfle, J, Berg, T, Keller, KM, et al. Persistent hepatitis G virus infection after neonatal transfusion. J Pediatr Gastroenterol Nutr 1998;26:402–7.Google Scholar
Naoumov, NV, Petrova, EP, Thomas, MG, et al. Presence of a newly described human DNA virus (TTV) in patients with liver disease. Lancet 1998;352:195–7.Google Scholar
Okamoto, H, Akahane, Y, Ukita, M, et al. Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis. J Med Virol 1998;56:128–32.Google Scholar
Koidl, C, Michael, B, Berg, J, et al. Detection of transfusion transmitted virus DNA by real-time PCR. J Clin Virol 2004;29:277–81.Google Scholar
Abzug, MJ. Prognosis for neonates with enterovirus hepatitis and coagulopathy. Pediatr Infect Dis J 2001;20:758–63.Google Scholar
Kawashima, H, Ryou, S, Nishimata, S, et al. Enteroviral hepatitis in children. Pediatr Int 2004;46:130–4.Google Scholar
Abzug, MJ. Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs 2004;6:1–10.Google Scholar
Pardi, DS, Romero, Y, Mertz, LE, et al. Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report of two cases and a review of the literature. Am J Gastroenterol 1998;93:468–70.Google Scholar
Granot, E, Miskin, H, Aker, M. Monoclonal anti-CD52 antibodies: a potential mode of therapy for parvovirus B19 hepatitis. Transplant Proc 2001;33:2151–3.Google Scholar
Tajiri, H, Tanaka-Taya, K, Ozaki, Y, et al. Chronic hepatitis in an infant, in association with human herpesvirus-6 infection. J Pediatr 1997;131:473–5.Google Scholar
Landing, BH. Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst: the concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 1974;4:113–39.Google Scholar
Steele, MI, Marshall, CM, Lloyd, RE, et al. Reovirus 3 not detected by reverse transcriptase-mediated polymerase chain reaction analysis of preserved tissue from infants with cholestatic liver disease. Hepatology 1995;21:697–702.Google Scholar
Tyler, KL, Sokol, RJ, Oberhaus, SM, et al. Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts. Hepatology 1998;27:1475–82.Google Scholar
Phillips, MJ, Blendis, LM, Poucell, S, et al. Syncytial giant-cell hepatitis: sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features. N Engl J Med 1991;324:455–60.CrossRefGoogle ScholarPubMed
Kahn, E, Greco, MA, Daum, F, et al. Hepatic pathology in pediatric acquired immunodeficiency syndrome. Human Pathol 1991;22:1111–19.Google Scholar
Poles, MA, Dieterich, DT, Schwarz, ED, et al. Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV). J AIDS Hum Retrovirol 1996;11:170–7.Google Scholar
Dworsky, M, Whitley, R, Alford, C. Herpes zoster in early infancy. Am J Dis Child 1980;134:618–19.Google Scholar
Costello, A, Dua, T, Duran, P, Gulmezoglu, M, Oladapo, OT, Perea, W, Pires, J, et al. Defining the syndrome associated with congenital Zika virus infection. Bull World Health Organ 2016;94:406–6A.Google Scholar
Rice, ME, Galang, RR, Roth, NM, Ellington, SR, Moore, CA, Valencia-Prado, M, Ellis, EM, et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection – U.S. Territories and Freely Associated States, 2018. MMWR Morb Mortal Wkly Rep 2018;67:858–67.CrossRefGoogle Scholar
Moore, CA, Staples, JE, Dobyns, WB, Pessoa, A, Ventura, CV, Fonseca, EB, Ribeiro, EM, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 2017;171:288–95.CrossRefGoogle ScholarPubMed
Wu, Y, Cui, X, Wu, N, Song, R, Yang, W, Zhang, W, Fan, D, et al. A unique case of human Zika virus infection in association with severe liver injury and coagulation disorders. Sci Rep 2017;7:11393.Google Scholar
Adebanjo, T, Godfred-Cato, S, Viens, L, Fischer, M, Staples, JE, Kuhnert-Tallman, W, Walke, H, et al. Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection – United States, October 2017. MMWR Morb Mortal Wkly Rep 2017;66:1089–99.Google Scholar
Fleming-Dutra, KE, Nelson, JM, Fischer, M, Staples, JE, Karwowski, MP, Mead, P, Villanueva, J, et al. Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with Possible Zika Virus Infection–United States, February 2016. MMWR Morb Mortal Wkly Rep 2016;65:182–7.Google Scholar
Laxer, RM, Roberts, EA, Gross, KR, et al. Liver disease in neonatal lupus erythematosus. J Pediatr 1990;116:238–42.CrossRefGoogle ScholarPubMed
Lee, LA, Sokol, RJ, Buyon, JP. Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics 2002;109:E11.CrossRefGoogle ScholarPubMed
Alpert, LI, Strauss, L, Hirschhorn, K. Neonatal hepatitis and biliary atresia associated with trisomy 17–18 syndrome. N Engl J Med 1969;280:16–20.CrossRefGoogle ScholarPubMed
Schwab, M, Niemeyer, C, Schwarzer, U. Down syndrome, transient myeloproliferative disorder, and infantile liver fibrosis. Med Pediatr Oncol 1998;31:159–65.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Pratt, DS. Cholestasis and cholestatic syndromes. Curr Opin Gastroenterol 2005;21:270–4.Google Scholar
van Mil, SW, Houwen, RH, Klomp, LW. Genetics of familial intrahepatic cholestasis syndromes. J Med Genet 2005;42:449–63.Google Scholar
Krantz, ID, Piccoli, DA, Spinner, NB. Alagille syndrome. J Med Genet 1997;34:152–7.Google Scholar
Bull, LN, van Eijk, MJ, Pawlikowska, L, et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 1998;18:219–24.Google Scholar
Vivarelli, R, Grosso, S, Cioni, M, et al. Pseudo-TORCH syndrome or Baraitser–Reardon syndrome: diagnostic criteria. Brain Dev 2001;23:18–23.Google Scholar
Sanchis, A, Cervero, L, Bataller, A, et al. Genetic syndromes mimic congenital infections. J Pediatr 2005;146:701–5.Google Scholar
Knoblauch, H, Tyennstedt, C, Brueck, W, et al. Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome). Am J Med Genet A 2003;120:261–5.Google Scholar
Hadzic, N, Portmann, B, Lewis, I, Mieli-Vergani, G. Coombs positive giant cell hepatitis: a new feature of Evans’ syndrome. Arch Dis Child 1998;78:397–8.CrossRefGoogle ScholarPubMed
Akylidiz, M, Karasu, Z, Arikan, C, et al. Successful liver transplantation for giant cell hepatitis and Coombs-positive haemolytic anemia: a case report. Pediatr Transplant 2005;9:630–3.Google Scholar
Balistreri, WF, Grand, R, Hoofnagle, JH, et al. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology 1996;23:1682–92.Google ScholarPubMed
Bates, MD, Bucuvalas, JC, Alonso, MH, et al. Biliary atresia: pathogenesis and treatment. Semin Liver Dis 1998;18:281–93.Google Scholar
Tazawa, Y, Abukawa, D, Maisawa, S, et al. Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and steatosis. Dig Dis Sci 1998;43:392–6.Google Scholar
Shet, TM, Kandalkar, BM, Vora, IM. Neonatal hepatitis: an autopsy study of 14 cases. Indian J Pathol Microbiol 1998;41:77–84.Google Scholar
Nishinomiya, F, Abukawa, D, Takada, G, et al. Relationships between clinical and histological profiles of non-familial idiopathic neonatal hepatitis. Acta Paediatr Jpn 1996;38:242–7.Google Scholar
Ruebner, B, Thaler, MM (1979). Giant-cell transformation in infantile liver disease. In Javitt, NB (Ed.) Neonatal Hepatitis and Biliary Atresia (pp. 299–314).Bethesda, MD: US Department of Health, Education and Welfare.Google Scholar
Park, WH, Kim, SP, Park, KK, et al. Electron microscopic study of the liver with biliary atresia and neonatal hepatitis. J Pediatr Surg 1996;31:367–74.Google Scholar
Moore, L, Bourne, AJ, Moore, DJ, et al. Hepatocellular carcinoma following neonatal hepatitis. Pediatr Pathol Lab Med 1997;17:601–10.Google Scholar
Suita, S, Arima, T, Ishii, K, et al. Fate of infants with neonatal hepatitis: pediatric surgeons’ dilemma. J Pediatr Surg 1992;27:696–9.Google Scholar
Dick, MC, Mowat, AP. Hepatitis syndrome in infancy: an epidemiological survey with 10 year follow-up. Arch Dis Child 1985;60:512–16.CrossRefGoogle Scholar
Lee, PI, Chang, MH, Chen, DS, et al. Prognostic implications of serum alpha-fetoprotein levels in neonatal hepatitis. J Pediatr Gastroenterol Nutr 1990;11:27–31.Google Scholar
Chang, MH, Hsu, HC, Lee, CY, et al. Neonatal hepatitis: a follow-up study. J Pediatr Gastroenterol Nutr 1987;6:203–7.Google Scholar
Deutsch, J, Smith, AL, Danks, DM, et al. Long-term prognosis for babies with neonatal liver disease. Arch Dis Child 1985;60:447–51.Google Scholar

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