50 Years Ago in The Journal of Pediatrics: Neonatal hepatitis in siblings

Abstract

Peterman MG. J Pediatr 1957;50:315-20 In 1957, M. G. Peterman reported two sets of siblings presenting in the neonatal period with cholestasis. With the limited available therapy, there was progression of disease leading to death. Common to all the cases was the presence of giant cell transformation of liver cells on post-mortem examination resulting in the diagnosis of neonatal hepatitis. Peterman described the diagnosis as a “general all-inclusive term, probably as satisfactory as any,” recognizing that the etiology was ill-defined. Over the last 50 years, cases of familial neonatal cholestasis have served as models to elucidate hepatic physiology, to identify specific genetic and molecular defects, and to expand the differential diagnosis of intrahepatic cholestasis presenting in the newborn period. This, in turn, has lead to improved diagnostic and therapeutic modalities. Many of the known genetic forms of intrahepatic cholestasis fall into broad categories of defects in embryogenesis, bile acid metabolism, and canalicular transport. Other causes of intrahepatic cholestasis include multi-organ disorders, metabolic diseases, and other clinically definable syndromes.1Balistreri W.F. Bezerra J.A. Whatever happened to “neonatal hepatitis”?.Clinics in Liver Disease. 2006; 10: 27-33Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Evaluation of infants presenting with conjugated hyperbilirubinemia has evolved to include recognition of the immature physiology of the newborn liver, evaluation for infection and metabolic disease, radiographic study of the biliary anatomy, and differentiation of intrahepatic cholestatic syndromes through a combination of clinical features, serum bile acid level, serum gamma glutamyl transpeptidase level, and liver biopsy. Diagnostic studies of the future include development of a gene chip, biomarkers of genetic defects, and targeted testing of molecular defects. Continued understanding of liver physiology and molecular pathophysiology of cholestatic disease has resulted in therapy to reduce symptoms, improve nutritional status, and delay progression of disease. These measures encompass medical therapy as well as surgical intervention including liver transplantation. The goal, however, should be to avoid the need for liver transplantation by defining and treating the underlying disease. Despite the progress over the last 50 years in diagnosis and treatment of neonatal hepatitis, approximately 15% of patients continue to be diagnosed with idiopathic disease.1Balistreri W.F. Bezerra J.A. Whatever happened to “neonatal hepatitis”?.Clinics in Liver Disease. 2006; 10: 27-33Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Clearer definition of phenotype, precise nomenclature of known diseases, and multi-center registries will be critical in improving diagnostic and treatment strategies in those with defined disease and in understanding the etiology of disease in those yet undiagnosed cases.