Related Experiment Video

Updated: Jun 28, 2026

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis
04:38

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Published on: March 28, 2018

Liver disease associated with ZZ alpha1-antitrypsin deficiency and ursodeoxycholic acid therapy in children

Panayotis Lykavieris1, Béatrice Ducot, Alain Lachaux

  • 1Pediatric Hepatology and National Reference Centre for Biliary Atresia, France.

Journal of Pediatric Gastroenterology and Nutrition
|October 29, 2008
PubMed

Insights

Ursodeoxycholic acid (UDCA) can improve liver health in children with ZZ alpha-1-antitrypsin (AAT) deficiency. However, it is less effective in severe cases, and initial liver enzyme levels can predict treatment success.

Area of Science:

  • Hepatology
  • Pediatric Gastroenterology
  • Genetic Liver Diseases

Background:

  • Alpha-1-antitrypsin (AAT) deficiency is a genetic disorder that can lead to progressive liver disease in children.
  • ZZ AAT deficiency is the most common severe genotype, often resulting in significant liver damage.
  • Ursodeoxycholic acid (UDCA) is a bile acid used to treat various liver conditions, but its efficacy in pediatric AAT deficiency-associated liver disease is not well-established.

Purpose of the Study:

  • To evaluate the therapeutic effect of ursodeoxycholic acid (UDCA) in pediatric patients diagnosed with liver disease secondary to ZZ alpha-1-antitrypsin (AAT) deficiency.
  • To identify predictors of treatment response to UDCA in this specific patient population.

Main Methods:

  • A cohort of 42 children with ZZ AAT deficiency-related liver disease received UDCA at a dosage of 30 mg/kg/day.
  • Patients were monitored with annual clinical and biochemical assessments.
  • Children were stratified into groups based on initial liver enzyme levels and treatment outcomes.

Main Results:

  • Children with lower initial gamma-glutamyl-transpeptidase (GGT) levels (Group 1) showed normalized liver tests after UDCA treatment, with sustained improvement even after discontinuation in some cases.
  • Patients with moderately elevated GGT (Group 2) experienced improved liver test results.
  • Children with the highest initial GGT levels (Group 3) did not benefit from UDCA and progressed to cirrhosis, necessitating liver transplantation in most.
  • Initial GGT and total bilirubin levels were significantly lower in responders compared to non-responders.
  • A combination of GGT ≤5.5xN and total bilirubin ≤66 µmol/L predicted normalization in 90% of cases.

Conclusions:

  • UDCA demonstrates potential to improve clinical status and biochemical markers in children with ZZ AAT deficiency-associated liver disease, particularly those with less severe initial liver involvement.
  • The effectiveness of UDCA is limited in children presenting with severe liver disease.
  • Baseline GGT and total bilirubin levels serve as valuable prognostic indicators for UDCA therapy response in this cohort.
Abstract

More Related Videos

Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology12:36

Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology

Published on: March 14, 2020

Related Concept Videos

Diseases of the Liver and Gallbladder01:26

Diseases of the Liver and Gallbladder

Liver and gallbladder diseases are a significant health concern, with prominent conditions including cirrhosis, hepatitis, non-alcoholic fatty liver disease (NAFLD), and gallstones. Jaundice is a common manifestation of liver and biliary disease.
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not related to...
Antiasthma Drugs: Leukotriene Modifiers01:19

Antiasthma Drugs: Leukotriene Modifiers

Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
Chronic Pancreatitis II: Pathophysiology01:21

Chronic Pancreatitis II: Pathophysiology

Chronic pancreatitis is a progressive and irreversible inflammation of the pancreas, most often caused by long-term alcohol abuse, but it can also be related to ductal obstruction, smoking, or genetic factors.Chronic pancreatitis occurs when the pancreas is repeatedly exposed to harmful agents like alcohol, smoking, ductal obstruction, or genetic predisposition. These factors lead to the release of toxic metabolites and inflammatory cytokines, sustaining chronic inflammation in the pancreatic...
Chronic Pancreatitis II: Collaborative Care01:29

Chronic Pancreatitis II: Collaborative Care

The management of chronic pancreatitis is multifaceted, involving a comprehensive approach that includes thorough assessment, diagnostic testing, and a variety of management strategies.
Assessment:
Cystic Fibrosis: Management01:24

Cystic Fibrosis: Management

Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic sinusitis...
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...