NAFLD Pediatric Database 2

All the new pediatric participants will have had a liver biopsy within 120 days prior to
enrollment coupled with contemporaneous biosamples within 90 days prior to enrollment and up
to 90 days before or 4-90 days after the biopsy. We estimate that at least 50 of the
continuing pediatric participants will be due for a standard of care liver biopsy at the time
of their enrollment into the pediatric Database 2 study, and will, as a result, also have a
liver biopsy and contemporaneous biosamples.

Inclusion Criteria:

- Continuing participants:

- Previously enrolled in the NAFLD Database study or TONIC trial

- Age at least 2 years and not older than 17 years during the consent process

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

- Ability and willingness to give written, informed parental consent and child
assent, per local IRB guidelines, to be enrolled into the pediatric Database 2
study

- New participants:

- Age at least 2 years of age and not older than 17 years during the consent
process

- Willingness to be followed for up to 4 years

- Ability and willingness to give written, informed parent consent and child assent
to be enrolled into the pediatric Database 2 study

- Minimal or no alcohol use history consistent with NAFLD

- Having undergone a 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:

- 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

- Cystic 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 of study

- Inability for parent to provide informed consent and child 8 years or greater to give
assent