Concise Pediatric and Adolescent Hepatology

A. Dhawan, A., Dhawan, Wieland Kiess, Wieland, Kiess

• Publisher: S. Karger
• Year: 2012
• Print ISBN:
  9783805598293
• eBook ISBN:
  9783805598309
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Great progress in molecular biology, therapeutics, imaging as well as surgery have vastly improved the understanding and treatment of childhood liver disorders. In particular, surgical advancements in liver transplantation currently allow for a lower age or weight limit for recipients. Furthermore, the majority of children with liver disease or with liver transplantation today survive well into adulthood. In this book, world experts in the now established subspecialty of pediatric hepatology provide a comprehensive summary of the latest advances in pathophysiology, molecular diagnostics and treatment strategies. Day-to-day management of liver transplant recipients as well as psychosocial aspects and complications during the challenging transition phase to adulthood are discussed in detail. This up-to-date overview will be an invaluable tool for trainees in pediatric gastroenterology, a ready reference for busy clinicians and nurses or allied health professionals involved in the care of children with liver disease and after liver transplantation.

Dhawan A (ed): Concise Pediatric and Adolescent Hepatology.
Pediatr Adolesc Med. Basel, Karger, 2012, vol 16, pp 175-201

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Intestinal Failure, Parenteral Nutrition and Liver Disease

Olivier J. Goulet

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Intestinal Failure Rehabilitation Center, National Reference Centre for Rare Digestive Diseases, Hospital Necker-Enfants Malades, University of Paris-Descartes, Paris, France

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Abstract

Intestinal failure (IF) is caused by the critical reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements for maintenance in adults and growth in children. A variety of congenital or acquired disorders may result in IF. The advent of parenteral nutrition (PN) resulted in a dramatic improvement in life expectancy of patients suffering IF, but it has its own complications, such as PN-related sepsis. With our current understanding of the genesis of IF-associated liver disease (IFALD), it should be prevented or at least early recognized and treated especially in patients experiencing prematurity and sepsis. New approach consisting in targeting harmful cytokine responses can be expected to reduce the severity and frequency of IFALD. In that view, prevention of sepsis, appropriate enteral feeding, treatment of intestinal bacterial overgrowth and the effects of fish oil in reversing cholestasis are promising. This chapter aims to review both IF and PN related factors of liver disease with special emphasize on inflammation as cause of liver injury.

Copyright © 2012 S. Karger AG, Basel

Intestinal failure (IF) is related to a variety of primary digestive diseases. Depending upon its cause, IF may be total or partial, permanent or provisional. Parenteral nutrition (PN) has allowed to improve the outcome after neonatal surgery for congenital abnormalities of the development of the GI tract with subsequent short bowel syndrome (SBS) or severe motility disorders such as extensive aganglionosis or chronic intestinal pseudo-obstruction [1-3]. Moreover, PN made possible the emergence and the diagnosis of rare congenital digestive diseases, especially those involving the development of intestinal mucosa [4] such as microvillous inclusion disease or microvillous atrophy [5, 6], epithelial dysplasia or tufting enteropathy [7, 8], syndromic diarrhea or tricho-hepatoenteric syndrome [9, 10].

Due to technical refinements and steady advances in the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients, PN has became a safe feeding technic and continue to play an important role in the management of many different patients. However, some complications, such as catheter-related sepsis (CRS) and cholestasis, continue at high incidence, particularly in neonates even during short course of PN [11-13]. Moreover, IF that requires long-term PN may be associated with various complications including CRS, growth failure, metabolic disorders, and bone disease. Cholestatic liver disease (CLD) was rapidly identified as one of the limiting factors of long-term IF management and is now considered as a major indication for intestinal transplantation or combined liver-intestine transplantation.

When assessing CLD, factors related to IF itself, those related to septic complications and the PN-related factors should always be considered separately. This makes wording very controversial for considering CLD that occurs during PN in children suffering IF complicated by sepsis. There is no doubt that CLD is multifactorial. In the past, PN itself was thought to be the main cause of liver disease in relation with inappropriate intake involving amino acids solution or deficiency in macro- and micronutrients or overload with potentially toxic components such as aluminium, iron or manganese [14-18]. Extensive literature including review papers and chapters of textbook have extensively listed the hypothetic factors of the so-called ‘PNRLD’ [19, 20]. Today, PN mixtures may be considered as very safe as soon as they are delivered appropriately according to guidelines [21]. The term ‘IF-associated liver disease’ (IFALD) seems more adapted than the term ‘parenteral nutrition-related liver disease’ (PNRLD) [22]. Interestingly, recent clinical data in infants with short bowel syndrome (SBS) focused on intravenous lipid emulsion (ILE) as an important factor of CLD [22]. They will be analyzed in this chapter. It is important to note that children demonstrate predominant cholestasis and more rapid progression to fibrosis and end stage liver disease while steatosis is the principal lesion in adults [19, 20]. In patients with SBS, liver dysfunction impairs the intestinal adaptation process which results in an even more prolonged need for PN. In that regard, series of paediatric patients with SBS, who required isolated liver graft for SBS having the potential of adaptation, were reported [23, 24].

Thus, both treatment and prevention of IFALD have the possibility to significantly reduce the need for liver transplantation isolated or combined with intestine and may enhance outcome of children with SBS. It is crucial to recognize early on, those patients who are at risk for developing liver disease [25, 26]. In the scope of this chapter, we will deal with the setting of long-lasting partial or total IF requiring longterm PN. However, some situations, such as prematurity, are no primarily related to IF and/or digestive disease making analysis and recommendations sometimes difficult in this age group. Indeed, what might be true for infants and children should be nuanced and adapted for premature babies.

Definition and Expression

IFALD may appear at any stage of PN and is defined clinically or biologically. However, diagnostic criteria for IFALD remain debated. The onset of clinical jaundice in a child within few weeks after starting on PN or during the course of long-term PN has been proposed. It is a late-onset criteria compared to biological changes. Clinical jaundice represents a major disturbance of liver function and occurs after protracted and serious effects on hepatic structure and function have occurred. The earliest manifestations of IFALD include an elevation in alkaline phosphatase or gamma glutamyl transferase within 7-14 days after starting PN. Increased plasma levels of transaminases are commonly observed at onset of PN especially in neonates and ICU patients. Elevated to greater than 1.5 times the upper limit of the reference range, for at least 2 weeks, in the absence of another cause (e.g. drug-induced disease, viral hepatitis, biliary obstruction, metabolic disorder) may be relevant [18-20]. The hepatic transaminases become elevated and to a lesser degree after 2-4 weeks and, thereafter, the liver function tests may stabilise to within the normal range unless an event such as surgery or a catheter infection occurs. The next significant alteration in liver biochemistry is a rise in conjugated bilirubin concentration. Elevated plasma bilirubin over 50, 70, 100 and 200 mmol/l (equivalent to 3, 4, 6 and 12 mg/dl) is recognized as the criteria for defining IFALD with a good sensitivity and specificity [28-30]. Finally, the most relevant assessment is based on liver biopsy, which is not performed routinely. There is no current recommendation for performing systematic liver biopsy except when intestinal transplantation (ITx) is discussed. Histopatological expression of liver disease includes steatosis, cholestasis and fibrosis with various degree of portal inflammation. In cases of severe cholestasis together with portal hypertension and its complications, liver biopsy is no longer necessary.

Hepatic Steatosis

Hepatic steatosis is the fatty infiltration of hepatocytes as the consequence of an excess calories (>8-12 mg/kg/h of glucose) causing hepatic accumulation of lipid or glycogen [27] (fig. 1). Parenteral carbohydrate calories in excess may be converted to triglyceride, by stimulating insulin release or by lipogenesis and the synthesis of acylglycerol from glucose [28]. Hepatic steatosis may appear early after starting TPN but is reversible after reduction of calories [29]. Steatosis may also be related to excess lipid infusions [30], as well as deficiencies of essential fatty acids, choline, taurine, or glutathione [31, 32]. Photoxidation of parenteral vitamins may cause hepatic steatosis as shown in pigs [33]. Hepatic steatosis is more common in adults and may develop without evidence of inflammation, cholestasis, or hepatocyte necrosis [29].

Cholestasis and Fibrosis

The deve...

Table of contents

• Cover Page
• Front Material
• Growing Up with Liver Disease - Psychological Aspects of Paediatric Liver Disease
• Acute Liver Failure in Children and Adolescents
• Progressive Familial Intrahepatic Cholestasis in Children
• Biliary Atresia
• Alagille Syndrome
• Immune Deficiency-Related Liver Disease
• Autoimmune Liver Disease
• Wilson Disease
• Non-Alcoholic Fatty Liver Disease in Children
• Non-Cirrhotic Portal Hypertension
• Primary Liver Malignancies: Surgical Aspects Including Transplantation
• Viral Hepatitis in Children
• Non-Viral Infections of the Liver
• Intestinal Failure, Parenteral Nutrition and Liver Disease
• Liver Transplantation
• Hepatocyte Transplantation, ‘Omics’ and Gene Therapy in the Management of Liver Diseases
• Author Index
• Subject Index