Hepatitis C virus (HCV) is an important cause of viral hepatitis in children and the actual number of infected children is clearly underestimated. HCV infection across the pediatric age spectrum differs from perinatal acquisition to infection acquired later in life; the modes of transmission, rates of spontaneous clearance or progression of fibrosis, the potential duration of chronic infection when acquired at birth, and, significantly, available treatment options also vary [1]. The discovery of HCV using molecular cloning techniques in 1989 led directly to an initial reduction in the number of acute HCV infections, and to the establishment of detection and treatment strategies. Mirroring the IV drug abuse epidemic, there has been a significant increase in reported HCV infections across all age groups over the last decade.

Biliary atresia and related disorders of the biliary tract, such as choledochal cysts, must be considered in the differential diagnosis of prolonged conjugated hyperbilirubinemia in the newborn (neonatal cholestasis).

Preface

Seven years have passed since the publication of the third edition of Liver Disease in Children. This text continues to be the premier, comprehensive reference on pediatric liver disease. Pediatric hepatology continues to grow and evolve as a distinct discipline and so it remains a challenge to provide comprehensive coverage without markedly increasing the length of this text. To keep the size of this textbook within limits, the number of references for each chapter has been limited to classical and the most relevant current citations. The editors felt that this was a reasonable compromise, since ready access to the literature is possible through resources such as PubMed.

We have appreciated the contributions of so many of our colleagues over the past two decades, but to ensure a fresh perspective and to involve experts who have emerged in the field, 11 of the chapters are written by authors contributing to this textbook for the first time. These contributors have provided particular expertise in areas such as liver development, autoimmune liver disease, intestinal failure-associated liver disease, fatty liver disease, and inborn errors of metabolism. There is also expanded coverage of liver transplantation.

Introduction

There is a wide spectrum of etiologically obscure inflammatory disorders of the biliary tract, including the obstructive cholangiopathies that occur in infancy (biliary atresia and related entities), primary biliary cirrhosis, which is noted in adults, and primary sclerosing cholangitis (PSC), which may affect patients of all age groups, particularly those with chronic inflammatory bowel disease (IBD). These hepatobiliary disorders differ markedly in clinical expression but display substantial overlap in morphologic features, suggesting that their pathogenesis may be shared. Because the intra- and extrahepatic biliary tree may be assumed to possess a limited repertoire of reactions to injury caused by various inflammatory mechanisms, the association of PSC and IBD may provide insight into other forms of “cholangitis.” The frequency of this association also presents an opportunity to trace the evolution of PSC. This chapter focuses on idiopathic forms of sclerosing cholangitis in children, the PSC–IBD complex, and related disorders.

Definition

Sclerosing cholangitis is a chronic hepatobiliary disorder characterized by inflammation of the intra- and/or extrahepatic ducts, leading to focal dilatation, narrowing, or obliteration accompanied by local periductular fibrosis. Progressive, obliterative fibrosis usually leads to biliary cirrhosis and end-stage liver disease. The structural abnormalities of larger bile ducts are best appreciated by cholangiography, which in most cases is essential in establishing the diagnosis. However, careful delineation of the histology of the hepatic parenchyma and smaller intrahepatic ducts may also suggest the diagnosis.