Last updated on February 2018

Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC)


Brief description of study

Cholestasis is a condition in which bile is not properly transported from the liver to the small intestine. Cholestasis can be caused by an array of childhood diseases, including the genetic diseases Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and progressive familial intrahepatic cholestasis (PFIC) or benign recurrent intrahepatic cholestasis(BRIC). This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.

Detailed Study Description

Cholestasis is a rare condition that involves a reduction or obstruction of bile flow from the liver to the small intestine. When bile flow is hindered, a waste product pigment called bilirubin can escape into the bloodstream and build up to harmful levels. This may lead to the easily recognizable cholestatic symptoms of jaundice, itching, and impaired growth and eventually to more serious health problems. Four rare genetic liver disorders ALGS, a-1AT, bile acid synthesis and metabolism defects, and PFICaccount for about 20% to 30% of all infant cases of cholestasis. These four disorders compose a group of related diseases that can cause significant growth problems during childhood, serious liver problems, the need for liver transplantation, and potentially death. More research on these rare liver diseases is necessary to develop a scientific basis for improvement in diagnostic techniques and treatments. Current diagnostic procedures are complex, and the development of simpler diagnostic tests would facilitate early diagnosis and treatment. This study will investigate the natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.

Participation in this study will last 10 years and will consist of a baseline visit and five annual follow-up visits. The study will enroll infants through adults 25 years of age who have, or are suspected of having, one of the four genetic cholestatic liver diseases. Individuals who are siblings of a-A1T participants and have underlying disease with no evidence of liver involvement may also be enrolled. Study visits will involve review of clinical information, family history, and any clinically indicated treatments and their outcomes; a physical exam; laboratory tests; and radiologic and imaging evaluations. In addition to these standard of care evaluations, participants will undergo several special research evaluations, including quality of life questionnaires, neurodevelopmental evaluations, hearing exams, DEXA scanning (dual energy x-ray absorptiometry), liver histology studies, and collection of serum, plasma, urine, and blood for DNA or cell lines. Serum, plasma, urine, and blood for DNA or cell lines will also be collected from both biological parents and from affected siblings of participants with a-A1T or ALGS. Genetic testing will be performed using the collected specimens.

Clinical Study Identifier: NCT00571272

Contact Investigators or Research Sites near you

Start Over

Kasper Wang, MD

Children's Hospital of Los Angeles
Los Angeles, CA United States
  Connect »

Peg Hill-Callahan, BS, LSW

University of California at San Francisco (UCSF)
San Francisco, CA United States
  Connect »

Ronald J. Sokol, MD

Children's Hospital Colorado
Aurora, CO United States
  Connect »

Saul Karpen, MD, PhD

Children's Healthcare of Atlanta
Atlanta, GA United States
  Connect »

Estella Alonso, MD

Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, IL United States
  Connect »

Jean Molleston, MD

Riley Hospital for Children
Indianapolis, IN United States
  Connect »

Peg Hill-Callahan, BS, LSW

Johns Hopkins University Hospital
Baltimore, MD United States
  Connect »

Jeff Teckman, MD

St. Louis University - Cardinal Glennon Children's Medical Center
Saint Louis, MO United States
  Connect »

Peg Hill-Callahan, BS, LSW

Washington University School of Medicine/St. Louis Children's Hospital
Saint Louis, MO United States
  Connect »

Peg Hill-Callahan, BS, LSW

Mount Sinai School of Medicine
New York, NY United States
  Connect »

Jorge Bezerra, MD

Cincinnati's Children's Memorial Hospital
Cincinnati, OH United States
  Connect »

Kathy Loomes, MD

Children's Hospital of Philadelphia
Philadelphia, PA United States
  Connect »

Robert Squires, MD

Children's Hospital of Pittsburgh
Pittsburgh, PA United States
  Connect »

Benjamin Shneider, MD

Baylor School of Medicine
Houston, TX United States
  Connect »

Stephen Guthery, MD

University of Utah
Salt Lake City, UT United States
  Connect »

Karen Murray, MD

Seattle Children's Hospital
Seattle, WA United States
  Connect »

Binita Kamath, MD

The Hospital for Sick Children
Toronto, ON Canada
  Connect »