Genetic Studies of Non-Alcoholic Fatty Liver Disease
Genetic Studies of Non-Alcoholic Fatty Liver Disease
Background:

 - Non-alcoholic fatty liver disease is the most common form of liver disease in the United
 States. It includes many conditions. Researchers want to study fatty liver disease by looking
 at people who have liver cirrhosis. They also want to look at people who are or were listed
 for liver transplants. Genetic studies may provide more information on the causes of these
 conditions.

 Objectives:

 - To study possible genetic causes of non-alcoholic fatty liver disease.

 Eligibility:

 - Individuals of any age who have non-alcoholic fatty liver disease and related conditions.

 Design:

 -  Participants will be screened with a physical exam and medical history.

 -  Participants will provide a blood sample for genetic testing. Liver tissue from a
 transplant or biopsy may also be studied.

 -  Participants may also be asked to have an imaging study of the liver. This imaging study
 may be an x-ray or magnetic resonance imaging.

 -  No treatment will be provided as part of this research study.
Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common form of liver disease in the
 United States. It includes a wide spectrum of conditions from benign hepatic steatosis to
 cirrhosis and liver failure. Non-Alcoholic Steatohepatitis (NASH) is a term that describes
 specific histological characteristics of liver inflammation and seems to be a determinant
 step in the progression of NAFLD to cirrhosis and liver failure. The overall purpose of this
 study is to increase our understanding of the genetic background and pathophysiology of NAFLD
 through detailed review of physical, radiologic and pathology characteristics, when
 available. We will perform genetic analysis of known and candidate genes and will assess
 inheritance through evaluation of unaffected relatives. Most patients will be seen by
 hepatologists in transplant centers and hepatology clinics across the country. A subset of
 patients and their families may be seen at the NIH Clinical Center.
-  INCLUSION CRITERIA:

 1. Although a liver biopsy is necessary to make the diagnosis of NASH, patients with
 radiologic evidence of fatty liver and/or cirrhosis in which other causes have
 been ruled out are eligible to participate.

 2. Patients who have already undergone liver transplantation for a confirmed
 diagnosis of NAFLD or cryptogenic cirrhosis are also eligible to participate.

 3. Depending on their willingness to participate, subjects may enroll in DNA
 laboratory-only or clinical-only. However, to conserve resources and meet study
 objectives, subjects with known pathogenic mutations will be given priority in
 selection for extensive clinical studies.

 4. Direct blood relatives (typically parents and siblings) of affected individuals
 with NAFLD and associated conditions are also eligible to participate.

 EXCLUSION CRITERIA:

 1. Anyone unwilling to provide informed consent (for themselves as adults, or on behalf
 of their children as minors) or assent.

 2. Pregnant women. Although fatty liver and cirrhosis are sometimes diagnosed during
 pregnancy, it is unclear if they were present before and just not diagnosed or if they
 develop as a complication of pregnancy. Additionally energy metabolism changes during
 pregnancy and lactation which may confound our analysis. If the condition persists
 after pregnancy and the diagnosis of NAFLD is

 clearly established, patients can be referred to the study.

 3. We will review a clinical description from the referring physician about a potential
 research subject to determine that the subject is appropriate to enter into the study.
 We reserve the right to exclude cases that are clearly not NAFLD or related to our
 direct research interests (e.g. fatty liver induced by chronic alcohol use, infectious
 causes, drug-related, or toxin-related). This almost never happens. However, as some
 of these environmental factors may contribute to a multifactorial etiology of hepatic
 changes, we may not exclude all such cases.