Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2

To add to the existing NAFLD Database an additional 1,500 adult participants with a diagnosis
of NAFLD, supported by a recent liver biopsy, with a broad range of severity. Core data
collection will include clinical, demographic, laboratory, imaging, and histological features

- To increase the population diversity of the NAFLD Database to provide greater
representation of Hispanic, Native American, African American, and Asian patients among
the new adult participants recruited into the NAFLD Database 2

- To expand the current specimen bank comprised of liver tissue, serum, plasma, and DNA
obtained from new participants and continuing participants undergoing repeat liver
biopsy with the specific goal of optimizing the collection of plasma or serum suitable
for biomarker development studies by obtaining specimens in close temporal proximity to
the performance of liver biopsy

Inclusion Criteria:

Continuing participants:

- Previously enrolled in the NAFLD Database study, PIVENS or TONIC trials

- Age at least 18 years during the consent process

- Willingness to continue to be followed for up to 4 years

- Ability and willingness to give written, informed consent to be enrolled into Database
2

New participants:

- Age at least 18 years during the consent process

- Willingness to be followed for up to 4 years

- Ability and willingness to give written, informed consent to be screened for and, if
eligible, to be enrolled into the Database 2 study

- Minimal or no alcohol use history consistent with NAFLD (see exclusion criteria)

- Collection of a standard of care liver biopsy that is obtained within 120 days of
enrollment

- Collection of biosamples (serum, plasma, DNA, and, if available, liver tissue) within
90 days prior to enrollment and 0-90 days before or 4-90 days after the standard of
care liver biopsy

Exclusion Criteria:

- Any condition or circumstances, which, in the opinion of the investigator, would
interfere with completion of scheduled follow-up visits and procedures for the
duration of the Database 2 study

- Clinical or histological evidence of alcoholic liver disease: Regular and
excessive use of alcohol within the 2 years prior to interview defined as alcohol
intake greater than 14 drinks per week in a man or greater than 7 drinks per week
in a woman. Approximately 10 g of alcohol equals one 'drink' unit. One unit
equals 1 ounce of distilled spirits, one 12-oz beer, or one 4-oz glass of wine

- Total parenteral nutrition for more than 1 month within a 6 month period before
baseline liver biopsy

- Short bowel syndrome

- History of gastric or jejunoileal bypass preceding the diagnosis of NAFLD.
Bariatric surgery performed following enrollment is not exclusionary. Liver
biopsies obtained during bariatric surgery cannot be used for enrollment because
of the associated surgical or anesthetic acute changes and the weight loss
efforts that precede bariatric surgery

- History of biliopancreatic diversion

- Evidence of advanced liver disease defined as a Child-Pugh-Turcotte score equal
to or greater than 10

- Evidence of chronic hepatitis B as marked by the presence of HBsAg in serum
(participants with isolated antibody to hepatitis B core antigen, anti-HBc total,
are not excluded)

- Evidence of chronic hepatitis C as marked by the presence of anti-HCV or HCV RNA
in serum

- Low alpha-1-antitrypsin level and ZZ phenotype (both determined at the discretion
of the investigator)

- Wilson's disease

- Known glycogen storage disease

- Known dysbetalipoproteinemia

- Known phenotypic hemochromatosis (HII greater than 1.9 or removal of more than 4
g of iron by phlebotomy)

- Prominent bile duct injury (florid duct lesions or periductal sclerosis) or bile
duct paucity

- Chronic cholestasis

- Vascular lesions (vasculitis, cardiac sclerosis, acute or chronic Budd-Chiari,
hepatoportal sclerosis, peliosis)

- Iron overload greater than 3+

- Zones of confluent necrosis, infarction, massive or sub-massive, pan-acinar
necrosis

- Multiple epithelioid granulomas

- Congenital hepatic fibrosis

- Polycystic liver disease

- Other metabolic or congenital liver disease

- Evidence of systemic infectious disease

- Known HIV positive

- Disseminated or advanced malignancy

- Concomitant severe underlying systemic illness that in the opinion of the
investigator would interfere with completion of follow-up

- Active drug use or dependence that, in the opinion of the study investigator,
would interfere with adherence to study requirements

- Any other condition, which in the opinion of the investigator would impede
compliance or hinder completion