Clinical trial NCT01030484: Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2
Official title: Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Disease
Keywords: NAFLD
NASH
non-alcoholic steatohepatitis
fatty liver disease
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-12-11
Enrollment: 2501
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: adult patients with suspected or known non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH)-related cirrhosis of the liver

Brief summary: The NAFLD Database 2 will recruit at least 1,500 new adult participants suspected or known to have NAFLD or nonalcoholic steatohepatitis (NASH)-related cirrhosis and will also invite adult participants from the prior NAFLD Database and related studies (PIVENS trial and TONIC trial) to enroll in the NAFLD Database 2. 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.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: Liver histology scores
timeFrame: varies
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Edward Doo, MD
role: STUDY_DIRECTOR
References:
citation: Sanyal AJ, Van Natta ML, Clark J, Neuschwander-Tetri BA, Diehl A, Dasarathy S, Loomba R, Chalasani N, Kowdley K, Hameed B, Wilson LA, Yates KP, Belt P, Lazo M, Kleiner DE, Behling C, Tonascia J; NASH Clinical Research Network (CRN). Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease. N Engl J Med. 2021 Oct 21;385(17):1559-1569. doi: 10.1056/NEJMoa2029349.
citation: Vilar-Gomez E, Gawrieh S, Liang T, McIntyre AD, Hegele RA, Chalasani N. Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD. J Clin Lipidol. 2021 Mar-Apr;15(2):275-291. doi: 10.1016/j.jacl.2020.12.010. Epub 2020 Dec 27.