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Citation
Tonascia, James (2024). Nonalcoholic Fatty Liver Disease Pediatric Database 2 (NAFLD Pediatric Database 2) (Version 1) [Dataset] NIDDK Central Repository. https://doi.org/10.58020/66r2-ab05
Data Availability Statement
Data from the Nonalcoholic Fatty Liver Disease Pediatric Database 2 (NAFLD Pediatric Database 2) [(Version 1) https://doi.org/10.58020/66r2-ab05] reported here are available for request at the NIDDK Central Repository (NIDDK-CR) website, Resources for Research (R4R), https://repository.niddk.nih.gov/.
Acknowledgment Statement
The NAFLD Pediatric Database 2 study was conducted by the study investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The resources from the NAFLD Pediatric Database 2 study reported here were supplied by NIDDK Central Repository (NIDDK-CR) and are available for request at https://repository.niddk.nih.gov. This manuscript was not prepared under the auspices of the NAFLD Pediatric Database 2 study and does not necessarily reflect the opinions or views of the NAFLD Pediatric Database 2 study, NIDDK-CR, or NIDDK.
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General Description

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated with fat accumulation that range from benign, non-progressive liver fat accumulation to severe liver injury, cirrhosis, and liver failure. NAFLD is highly prevalent within the United States and is most common in adults who are overweight or have diabetes, insulin resistance, or hyperlipidemia. However, the disease also occurs in children and in persons who are not obese or diabetic. The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to conduct multicenter, collaborative studies on the etiology, contributing factors, natural history, complications and treatment of NASH.

The NAFLD Pediatric Database 2 was a multicenter, prospective follow-up study of patients with NAFLD or nonalcoholic steatohepatitis (NASH) which aimed to investigate the etiology, pathogenesis, natural history, diagnosis, treatment, and prevention of NAFLD and NASH. The study included longitudinal follow-up of participants enrolled in earlier NASH CRN studies and recruited new participants. The study population included pediatric patients 2- 17 years old at the time of enrollment with histologically confirmed NAFLD or NASH located in the United States. Comprehensive data, including demographics, medical history, symptoms, medication use, alcohol use and routine laboratory studies was collected on all participants at entry and at follow-up visits every 48 weeks from enrollment. A standard of care liver biopsy was collected at baseline if not previously collected, and specimens were collected every 48 weeks during follow-up.

Objectives

Primary objective(s): The NAFLD Pediatric Database 2 study aimed to elucidate, through the cooperative effort of a multidisciplinary and multicenter group of collaborators, the etiology, natural history, diagnosis, treatment, and prevention of NAFLD, and in particular its more severe form of NASH and its complications. Additional primary objectives included enrolling at least 650 pediatric patients with a diagnosis of NAFLD; increasing the population diversity of the NAFLD Database to provide greater representation of Hispanic, Native American, African American, and Asian patients; and expanding the specimen bank comprised of liver tissue, serum, plasma, and DNA obtained from patients undergoing a liver biopsy.

Secondary objective(s): The secondary objectives of the NAFLD Pediatric Database 2 were to continue the analysis of the data obtained in the previous NAFLD Database study; to add to current NASH CRN resources for developing clinical and pathological criteria for standardizing diagnostic and staging criteria for NAFLD or NASH-related cirrhosis; to develop Magnetic Resonance Imaging (MRI) or Magnetic Resonance Spectroscopy (MRS) protocols to evaluate the utility of these diagnostic modalities for the non-invasive staging and grading of NAFLD; and to add to NASH CRN resources for ancillary studies of the pathogenesis, diagnosis or diagnostic biomarker development, genomic, proteomic and lipidomic characterization, natural history and treatment of NAFLD or NASH-related cirrhosis.

Outcome Measure

The following measures were used to assess primary and secondary outcomes of interest: liver histology scores (derived from central reading of standard of care biopsy done during screening or follow-up), change in ALT and AST levels, change in glucose and insulin levels, change in lipid profiles, and change in body mass index (BMI) and anthropometric data.

Eligibility Criteria

Inclusion criteria:

  • At least 2 years of age and up to 17 years of age as of the initial screening interview and provision of consent
  • Willingness to participate in the study for 1 or more years
  • Having undergone liver biopsy within 120 days of enrollment
  • Collection of serum and plasma up to 90 days before or 4- 90 days after standard of care liver biopsy
  • Minimal or no alcohol use history consistent with NAFLD

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
Outcome

A total of 971 participants (101 of which were continuing participants from prior NASH CRN studies) were included in the NAFLD Pediatric Database 2. Data collection began on October 5, 2009 and concluded on May 31, 2020. The histologic scoring system for review and grading of liver biopsies was further refined and expanded, and participants are being followed into adulthood, to better understand the natural history of NAFLD during the adolescent to adult transition. Participants will continue to be followed in NAFLD Pediatric Database 3 study (DB3), the third phase of the longitudinal NAFLD database study.

Research Area

Liver Disease

Study Type

Observational

Study Start Date

2010-01

Study End Date

2020-05

Condition

Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis, Cirrhosis of Liver, Fatty Liver Disease, Fibrotic Liver Disease

Keywords

Liver Histology Scores , Glucose, Disease Etilogy, Cirrhosis, Nonalcoholic Fatty Liver Disease, Fat Accumulation, Non-Alcoholic Steatohepatitis

NIDDK Division

DDN

857
Participants

Target Population
Children
Age statistics is not available for this study
Location statistics is not available for this study

Public Documents Table
Document Name
Description
Document Type
File Format
Compliance
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Datasets (23)
Datasets Table
Dataset Name
Description
# of Records
# of Variables
File Format(s)
LS - Laboratory Results - Tests Done only During Screening (Revision 3) Data
Data collected to record archival and current results of laboratory tests done only during screening44sas7bdat (128 KB); csv (6.7 KB)
IE - Interim Event Report (Revision 2) Data
Data collected to document events that occur after registration that impact on the patient’s participation in the NAFLD Database 2 Study (eg, mild or moderate liver biopsy complications). Complete this form if there has been an incident cirrhosis, hepatocellular carcinoma (HCC), hospitalization, Emergency Room visit, liver transplant, an event associated with a study-related procedure, or death3sas7bdat (128 KB); csv (335 B)
RG - Registration Data
Data collected to register patients as candidates for enrollment in the NAFLD Database 2 study and to assign a patient ID number857sas7bdat (320 KB); csv (57.59 KB)
LR - Laboratory Results - Tests Done During Screening and Follow-up (Revision 2) Data
Data collected to record archival and current laboratory test results for tests done during both screening and follow-up1737sas7bdat (640 KB); csv (260.47 KB)
LR - Laboratory Results - Tests Done During Screening and Follow-up (Revision 1) Data
Data collected to record archival and current laboratory test results for tests done during both screening and follow-up135sas7bdat (128 KB); csv (19.96 KB)
IE - Interim Event Report (Revision 3) Data
Data collected to document events that occur after registration that impact on the patient’s participation in the NAFLD Database 2 Study (eg, mild or moderate liver biopsy complications). Complete this form if there has been an incident cirrhosis, hepatocellular carcinoma (HCC), hospitalization, Emergency Room visit, liver transplant, an event associated with a study-related procedure, or death289sas7bdat (128 KB); csv (22.33 KB)
BG - Baseline History (Revision 1) Data
Data collected on baseline medical history information about the patient91sas7bdat (312 KB); csv (43.82 KB)
IR - Liver Imaging Studies Report Data
Data collected to record liver imaging results473sas7bdat (320 KB); csv (43.9 KB)
CG - Genetic Consent and Blood Collection Documentation (Revision 1) Data
Data collected to document options selected for use of blood samples for genetic research682sas7bdat (128 KB); csv (18.79 KB)
PE - Physical Examination Data
Data collected to record physical exam findings of NAFLD Database 2 patients3144sas7bdat (896 KB); csv (393.45 KB)
AD - Alcohol Use Disorders Identification Test (AUDIT) Data
Data collected to screen for current heavy drinking and/or active alcohol abuse or dependence540sas7bdat (128 KB); csv (16.1 KB)
LS - Laboratory Results - Tests Done only During Screening (Revision 1) Data
Data collected to record archival and current results of laboratory tests done only during screening636sas7bdat (320 KB); csv (85.29 KB)
LD - Lifetime Drinking History (Skinner) Data
Data collected to obtain quantitative indices of the patient's alcohol consumption patterns from the onset of regular drinking8sas7bdat (128 KB); csv (2.8 KB)
CG - Genetic Consent and Blood Collection Documentation (Revision 2) Data
Data collected to document options selected for use of blood samples for genetic research223sas7bdat (128 KB); csv (6.39 KB)
HI - Follow-Up Medical History Data
Data collected to record follow-up medical history information about the patient2317sas7bdat (1.31 MB); csv (591.18 KB)
Central Histology Review (Revision 4) Data
Data collected to record results of the NASH CRN Pathology Committee review of liver biopsy slides archived at the Histology Review Center3sas7bdat (128 KB); csv (386 B)
Central Histology Review (Revision 2) Data
Data collected to record results of the NASH CRN Pathology Committee review of liver biopsy slides archived at the Histology Review Center454sas7bdat (128 KB); csv (37.08 KB)
BQ - Beverage Questionnaire (BEVQ-15) Data
Data collected to obtain the patient's beverage intake1146sas7bdat (192 KB); csv (85.66 KB)
IE - Interim Event Report (Revision 1) Data
Data collected to document (1) events that occur after registration but before enrollment, or between regular follow-up visits, that impact on the patient’s participation in the NAFLD Database 2 Study (eg, mild or moderate liver biopsy complications), or (2) other event that clinical center staff feel should be reported now rather than wait until the next follow-up visit and that is not recorded on another NAFLD Database 2 form115sas7bdat (128 KB); csv (7.12 KB)
LS - Laboratory Results - Tests Done only During Screening (Revision 2) Data
Data collected to record archival and current results of laboratory tests done only during screening191sas7bdat (192 KB); csv (28.5 KB)
LR - Laboratory Results - Tests Done During Screening and Follow-up (Revision 3) Data
Data collected to record archival and current laboratory test results for tests done during both screening and follow-up1264sas7bdat (512 KB); csv (196.51 KB)
BG - Baseline History (Revision 2) Data
Data collected on baseline medical history information about the patient766sas7bdat (1.16 MB); csv (351.23 KB)
Central Histology Review (Revision 3) Data
Data collected to record results of the NASH CRN Pathology Committee review of liver biopsy slides archived at the Histology Review Center356sas7bdat (128 KB); csv (23.51 KB)
Specimens (73,557)
Specimens Table
Specimen
Count
Plasma21181
Serum52376