Maternal-fetal transmission of hepatitis C infection: what is so special about babies?

Children with hepatitis C virus infection often differ from adults regarding the rate of viral clearance, duration of infection, and the progression to cirrhosis. In the pediatric population, vertical transmission of hepatitis C virus infection from mother to infant is the most common route of infection. In the present review, we explore the factors that may influence the natural history of hepatitis C virus infection in children who acquire the infection through maternal-fetal transmission. There is particular focus on how viral diversity and the infant immune system may affect viral transmission. An enhanced understanding of maternal-fetal transmission of hepatitis C virus infection has the potential to affect effective drug and vaccine development for both children and adults.

Kidney and liver transplantation in children with fibrocystic liver-kidney disease: data from the US Scientific Registry of Transplant Recipients: 1990-2010.

The natural history and survival of children with fibrocystic liver-kidney disease undergoing solid organ transplantation have infrequently been described. We report outcomes in a cohort of US children with fibrocystic liver-kidney disease receiving solid organ transplants over 20 yr. Retrospective cohort study of pediatric transplant recipients with diagnoses of fibrocystic liver-kidney disease from 1/1990 to 3/2010, using data from the SRTR. Subjects were categorized by the first transplanted organ: LT, KT, or SLK. Primary outcomes were death, re-transplant, transplant of the alternate organ, or initiation of dialysis. Seven hundred and sixteen subjects were transplanted in this period. Median age at first transplant was 9.7 yr. Of the LT, 14 (19%) required a second liver transplant at median of 0.2 yr, and five (7%) required kidney transplant or dialysis at a median of 9.0 yr. Of the KT, 188 (31%) required a second kidney transplant or dialysis at a median of 5.9 yr. Twenty-nine (5%) subsequently received liver transplant at a median of 6.0 yr. Among patients in this registry, far more children underwent kidney than liver transplants. The risk of subsequently needing transplantation of an alternate organ was low.

Liver transplantation in a child with multifocal hepatocellular carcinoma hepatitis C and management of post-transplant viral recurrence using boceprevir.

HCV infection is the leading cause of liver transplantation in the adult population in the United States. HCV infection occurs in 0.2-0.4% of the pediatric population and progression to HCC is uncommon. Liver transplantation for HCV in children is rare. In this report, we present a case of pediatric patient with HCV and multifocal HCC at the age of 13 who underwent successful liver transplantation. While good graft function was initially observed, at one month after transplant, he experienced significant hepatitis C recurrence. He was treated with low-accelerating dose regimen antiviral therapy of PEG-IFN and RBV, followed by addition of a protease inhibitor, boceprevir, which led to viral clearance. To our knowledge, this is the first case report describing the post-transplant course of a child transplanted for HCV and HCC, and the first pediatric case report on using the triple therapy for management of post-liver transplant recurrence of HCV. This case report demonstrates the need for increased vigilance of surveillance for HCC during childhood.

An Atypical Presentation of Alagille Syndrome.

Alagille syndrome is a multisystem disorder classically involving the liver, heart, vertebrae, facial features, and the eyes. In this case report, we document a case of Alagille syndrome with an atypical clinical and histopathologic presentation and subsequent identification of a novel JAG1 missense mutation. This case highlights that there may be both atypical clinical and pathologic findings in mutation-proven Alagille syndrome and that the diagnosis of Alagille syndrome should be considered in cases of ongoing bile duct damage in the setting of early-onset jaundice, cholestasis, hepatosplenomegaly, posterior embryotoxon in the eyes, and butterfly vertebrae.

Isolation of rat portal fibroblasts by in situ liver perfusion.

Liver fibrosis is defined by the excessive deposition of extracellular matrix by activated myofibroblasts. There are multiple precursors of hepatic myofibroblasts, including hepatic stellate cells, portal fibroblasts and bone marrow derived fibroblasts. Hepatic stellate cells have been the best studied, but portal fibroblasts are increasingly recognized as important contributors to the myofibroblast pool, particularly in biliary fibrosis. Portal fibroblasts undergo proliferation in response to biliary epithelial injury, potentially playing a key role in the early stages of biliary scarring. A method of isolating portal fibroblasts would allow in vitro study of this cell population and lead to greater understanding of the role portal fibroblasts play in biliary fibrosis. Portal fibroblasts have been isolated using various techniques including outgrowth and liver perfusion with enzymatic digestion followed by size selection. The advantage of the digestion and size selection technique compared to the outgrowth technique is that cells can be studied without the necessity of passage in culture. Here, we describe a modified version of the original technique described by Kruglov and Dranoff for isolation of portal fibroblasts from rat liver that results in a relatively pure population of primary cells.