Genetic Studies of Non-Alcoholic Fatty Liver Disease

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.