Nonalcoholic Fatty Liver Disease (NAFLD) Database 3

The NAFLD Database 3 will enroll approximately 1500 adult patients and 750 pediatric patients suspected or known to have NAFLD or NASH-related cirrhosis. 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.

Study Overview

• Status: Completed
• Conditions: Liver Diseases

Detailed Description

This is a multicenter, prospective follow-up study of patients with known nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). The primary objective of the study is to investigate the etiology, pathogenesis, natural history, diagnosis, treatment, and prevention of NAFLD and NASH.

• Study Type: Observational
• Enrollment (Actual): 1649

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92103
      • University of California, San Diego- Adults
    • Los Angeles, California, United States, 90089
      • University of Southern California
    • San Diego, California, United States, 92103
      • University of California, San Diego Pediatrics
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University-Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
    • Indianapolis, Indiana, United States, 46202
      • Indiana University- Adults
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital, Baylor University
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital- SEA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be at least 2250 patients age 2 years or older with histologically confirmed NAFLD or NASH located in the United States:

• 1500 patients 18 years and older at the time of enrollment.
• 750 patients 2 years or older and up to 17 years old at the time of enrollment.

Description

Inclusion Criteria:

• 2 years of age or older as of the initial screening interview and provision of consent
• Willingness to participate in the study for 1 or more years
• Histologic evidence of NAFLD or NASH based upon a standard of care liver biopsy
• Collection of serum and plasma up to 90 days before or 4- 90 days after standard of care liver biopsy
• Absence of regular or excessive use of alcohol within 2 years prior to initial screening

Exclusion Criteria:

• 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 (patients 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 of study
• Inability to complete the appropriate informed consent process

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Adult patients with NAFLD; 1500 patients 18 years and older at the time of enrollment.
Pediatric patients with NAFLD; 750 patients 2 years or older and up to 17 years old at the time of enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in alanine aminotransferase (ALT) levels from baseline to one year.	ALT measure in IU/L (higher ALT indicates worse outcomes)	Baseline and 1 year

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Baylor College of Medicine; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of California, San Diego; Emory University; Duke University; University of Southern California; Seattle Children's Hospital; University of California, San Francisco; Ann & Robert H Lurie Children's Hospital of Chicago; Children's Hospital Medical Center, Cincinnati; Virginia Commonwealth University; Indiana University; Case Western Reserve University; St. Louis University; Liver Institute Northwest
• Investigators: Principal Investigator: Arun Sanyal, MD, Virginia Commonwealth University Medical Center; Principal Investigator: Brent Tetri, MD, St Louis University Hospital

Publications and helpful links

Helpful Links

• Nonalcoholic Steatohepatitis Clinical Research Consortium
• NIDDK Central Repository

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): July 9, 2025
• Study Completion (Actual): July 9, 2025

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: NAFLD; NASH; non-alcoholic steatohepatitis; fatty liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NAFLD Database 3; U24DK061730 (U.S. NIH Grant/Contract); U01DK061732 (U.S. NIH Grant/Contract); U01DK061713 (U.S. NIH Grant/Contract); U01DK061737 (U.S. NIH Grant/Contract); U01DK061728 (U.S. NIH Grant/Contract); U01DK061718 (U.S. NIH Grant/Contract); U01DK061734 (U.S. NIH Grant/Contract); U01DK061738 (U.S. NIH Grant/Contract); U01DK061731 (U.S. NIH Grant/Contract); IRB00242326 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The NASH CRN is fully committed to resource sharing beyond the NASH CRN investigators. The NASH CRN will make deposits to the NIDDK Central Data Repository according to the requirements outlined in the NIDDK Data Sharing Policy published in July 2013.
• IPD Sharing Time Frame: Within two years of end of the funding cycle.
• IPD Sharing Access Criteria: All qualified investigators will be allowed access to the stored materials at the end of a pre-determined proprietary period.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No