Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC)

General Description

Cholestasis, a rare condition involving a reduction or obstruction of bile flow from the liver to the small intestine, can cause significant growth problems, liver complications, the need for liver transplantation, and death. The four rare genetic disorders Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis defects, and progressive familial intrahepatic cholestasis (PFIC) account for approximately 20% to 30% of all infant cases of cholestasis. Current knowledge concerning the etiology and outcomes of these diseases is limited. The Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC) study is a longitudinal cohort study that was established by the Childhood Liver Disease Research and Education Network (ChiLDReN) to investigate the natural history and progression of these four genetic disorders.

Children and adults ages 6 months through 25 years who have been diagnosed with ALGS, a-1AT deficiency, bile acid synthesis defects, and PFIC are enrolled. Individuals who are siblings of a-A1T participants and have underlying disease with no evidence of liver involvement may also be enrolled. Participants will complete a baseline visit and give annual follow-up visits. Study visits involve review of clinical information, family history, and any treatments and their outcomes. A physical exam, laboratory tests, and radiologic and imaging evaluations will also be performed. In addition to these standard of care evaluations, participants will undergo neurodevelopment evaluations, DEXA scanning, hearing exams, and liver histology studies. The primary outcome measure is the evaluation of disease progression for each condition, which includes assessment of growth failure, worsening liver functions, developmental complications of portal high blood pressure, liver transplantation, and death. Jaundice, listing for liver transplantation, calculated pediatric end-stage liver disease (PELD) score or model for end-stage liver disease (MELD) score, health-related quality of life, growth, bone mineral density, and presence of hearing loss are assessed as secondary outcome measures.

The data package now includes analysis datasets from multiple publications.

Objectives

The primary objectives of the LOGIC study include determining the frequency of poor growth and decreased bone mineral density and its predictors; identifying modifier genes that influence the incidence, severity, and progression of liver disease among affected individuals; and developing a repository of biospecimens to be used in ancillary studies of predictor biomarkers.

Outcome Measure

The primary outcome measure is the evaluation of disease progression for each condition, which includes assessment of growth failure, worsening liver functions, developmental complications of portal high blood pressure, liver transplantation, and death. Jaundice, listing for liver transplantation, calculated pediatric end-stage liver disease (PELD) score or model for end-stage liver disease (MELD) score, health-related quality of life, growth, bone mineral density, and presence of hearing loss are assessed as secondary outcome measures.

Criteria

Children and young adults between the ages of 6 months and 25 years who are diagnosed with Alagille syndrome (ALGS), alpha-1 antitrypsin (a-1AT) deficiency, bile acid synthesis and metabolism defects, and progressive familial intrahepatic cholestasis (PFIC) are enrolled. Siblings of participants with a-1AT deficiency who themselves have a-1AT deficiency of liver disease may also be enrolled.

Outcome

This study is ongoing.