Nonalcoholic Fatty Liver Disease Adult Database 3 (NAFLD Adult Database 3)

General Description

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions that can progress to significant fibrosis and cirrhosis. There are an estimated 40-90 million individuals within the United States with NAFLD, 10- 30% of whom have NASH and may develop NASH-related cirrhosis. Identifying through non-invasive means those individuals who are at risk for progressive liver disease remains challenging. 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 Database 3 is a multicenter, prospective follow-up study of patients with NAFLD or nonalcoholic steatohepatitis (NASH) which aims to investigate the etiology, pathogenesis, natural history, diagnosis, treatment, and prevention of NAFLD and NASH. The study will continue the longitudinal follow-up of participants enrolled in earlier NASH CRN studies and recruit new participants. The study population will include at least 1500 adult patients age 18 years or older 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 will be collected on all participants at entry and at follow-up visits every 48 weeks from enrollment. A standard of care liver biopsy will be collected at baseline if not previously collected, and specimens will be collected every 48 weeks during follow-up.

Objectives

Primary objective(s): The NAFLD Database 3 study aims 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 include enrolling at least 1500 adult patients with a diagnosis of NAFLD; increasing the population diversity of the NAFLD Database 2 to provide greater representation of Hispanic, Native American, African American, and Asian patients; and expanding the current 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 Database 3 are to continue the analysis of the data obtained in the NAFLD Database 2 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 add to current NASH CRN resources for developing clinical and pathological criteria and measures and endpoints for therapeutic studies of NAFLD or NASH-related cirrhosis; to evaluate the utility of FibroScan® as a diagnostic modality for the non-invasive staging and grading of NAFLD; and to add to current 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 will be 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, change in body mass index (BMI) and anthropometric data, change in alcohol consumption, change in medication use, change in liver symptoms, change in anxiety and depression scores, and change in measures of impulsivity.

Criteria

Inclusion criteria:

• 18 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 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

Outcome

This study is ongoing.