Autoimmune Liver Disease

Management and Clinical Practice

James Neuberger, Gideon M. Hirschfield, James Neuberger, Gideon M. Hirschfield

• Publisher: Wiley-Blackwell
• Year: 2020
• Print ISBN:
  9781119532606
• eBook ISBN:
  9781119532620
• Edition: 1
• Topic: Medicine
• Subtopic: Gastroenterology & Hepatology

A practical guide to autoimmune liver diseases through pathogenesis, diagnosis, and management

In Autoimmune Liver Disease Management and Clinical Practice, practitioners will learn about the current state of autoimmune liver disease and how to focus on their diagnosis and treatment. The four-part book begins with a thorough investigation of current immunological thinking as it relates to the autoimmunity of the liver. It also covers the four major hepatic autoimmune liver diseases in both adults and children, their management and the role of liver transplantation, and learned approaches to patient management and empowerment.

Expert authors in the field have come together to provide a thorough examination of autoimmune liver disease to help support clinicians assisting patients. The text provides an in-depth look at topics including:

?      The four major hepatic autoimmune liver diseases, their diagnosis, and potential disease management

?      The use (and misuse) of autoantibodies in diagnosis and treatment

?      The role and timing of liver transplantation and the impact of recurrent autoimmune liver disease as well as de novo autoimmune hepatitis

?      Optimal approaches to managing patients and keeping care personalised

With breadth, depth and current-day relevance, Autoimmune Liver Disease sheds light on recent developments in management of liver disease for practitioners, nurses, and health care professionals.

Section I
Scientific Basis of Clinical Autoimmune Liver Diseases

1
Introduction to the Physiology, Immunology and Pathology of the Liver and Biliary Tree

Marco Carbone¹ and Mario Strazzabosco²

¹ Division of Gastroenterology, University of Milan Bicocca, Milan, Italy

² Digestive Disease Section, Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA

Abstract

The liver has many functions including metabolic homeostasis, disposal of endotoxins and xenotoxins, metabolism of bilirubin and urea, and bile formation and secretion. The process of bile formation depends on the liver synthesis and the canalicular secretion of bile acids. Besides their roles in dietary lipid absorption and cholesterol homeostasis, bile acids also play a key role as signaling molecules in the regulation of hepatic metabolism and energy homeostasis. The regenerative ability of the liver lies in the multiple niches of biliary tree stem cells.

Keywords bile formation; carbohydrate metabolism; hepatocyte; cholangiocytes lipid metabolism; metabolic zonation; protein metabolism; bile acid.

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Key Points

• The liver is largely composed of hepatocytes and biliary epithelial cells or cholangiocytes; both hepatocytes and intrahepatic cholangiocytes differentiate from bipotent liver progenitors, the hepatoblasts.
• The liver has many functions, among which metabolic homeostasis, disposal of endotoxins and xenotoxins, metabolism of bilirubin and urea, and bile formation and secretion are just examples. The liver also produces fundamental circulating proteins and clotting factors and hormones. In addition, the liver receives and processes the blood coming from the intestine and has a fundamental role in innate immunity.
• Besides their roles in dietary lipid absorption and cholesterol homeostasis, bile acids (BAs) also play a key role as signaling molecules in the regulation of hepatic metabolism and energy homeostasis.
• BAs also have hormonal signaling functions and interact with dedicated receptors such as the nuclear receptor farnesoid X receptor and G protein‐coupled receptors, which regulate BA homeostasis and BA‐induced injury and/or inflammation.
• Multiple niches of biliary tree stem/progenitor cells reside in different locations along the human biliary tree and within the liver parenchyma and have a key role in regeneration of the liver.
• Cholangiocytes modify the primary bile by secretion of chloride and bicarbonate fluid. This is a major protective mechanism for the biliary tree.
• Cholangiocytes, a barrier and secretory epithelium in normal conditions, activate and/or proliferate following a liver insult and give rise to the ductular reaction, a major driver of the progression of hepatic fibrosis.
• Cholangiocytes also contribute to the immune response through antigen presentation to immune cells, being a target of immune‐mediated aggression or being the initiators of an inflammatory reaction that then progresses to adaptive immune activation.

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Liver Cell Types and Organization

Liver cells can be classified into the following groups:

• parenchymal cells, which include hepatocytes and biliary epithelial cells (BECs);
• sinusoidal cells, which include hepatic sinusoidal endothelial cells and Kupffer cells; and
• perisinusoidal cells, which include the hepatic stellate cells (HSCs) and the pit cells [1].

The hepatocytes, which comprise approximately 60% of the liver cell mass, are epithelial cells with two distinct domains on their plasma membrane: (i) the sinusoidal (or basolateral) surface, facing the sinusoids, in contact with plasma through the fenestrated endothelium of the sinusoids, which allows a bidirectional flow of liquids and solutes though the space of Disse; and (ii) the canalicular (or apical) surface, which encloses the bile ductules and represents the beginning of the biliary drainage system.

The BECs (or cholangiocytes) are the epithelial cells lining the biliary tree. The biliary epithelium shows a morphologic heterogeneity that is associated with a variety of functions performed at the different levels of the biliary tree. Other than funneling bile into the intestine, BECs are actively involved in bile production by performing both absorptive and secretory functions via various membrane transport mechanisms including channels (e.g. water channels and chloride channels), transporters (e.g. ileal BA transporter), and exchangers (e.g. Cl⁻/HCO3⁻ or Na⁺/H⁺ exchangers). The large cholangiocytes are located at the level of interlobular and major bile ducts and they express several different ion channels and transporters at the basolateral or apical domain; they are believed to be mostly involved in secretin/cyclic AMP‐regulated bile secretion. Smaller bile duct branches include terminal cholangioles and ductules or canals of Hering; the latter is a channel located at the ductular–hepatocellular junction, lined partly by hepatocytes and partly by cholangiocytes, and represents the physiologic link between the biliary tree and the hepatocyte canalicular system extended within the lobule. Their secretory function is believed to be mostly reg...

Table of contents

• Cover
• Table of Contents
• Preface
• Contributors
• Abbreviations
• Introduction
• Section I: Scientific Basis of Clinical Autoimmune Liver Diseases
• Section II: Autoimmune Liver Diseases and Their Clinical Correlation
• Section III: Specific Clinical Challenges
• Section IV: Transplantation and Its Role in Autoimmune Liver Disease
• Section V: Controversies in Autoimmune Liver Diseases
• Index
• End User License Agreement