Clinical Trials

Inclusion Criteria:

• At least 18 years of age at time of initial screening.
• Written informed consent to participate.
• Willingness to be followed for up to minimum 4 years.
• Minimal or no alcohol use history consistent with NAFLD
• Participant may either have a clinical diagnosis of NAFLD-cirrhosis or have undergone a liver biopsy within 180 days of enrollment as part of standard of care.
• Collection of biosamples (serum, plasma, urine, DNA, and if available, liver tissue) within 180 days of enrollment.
• Patients with either biopsy-proven NAFLD, or patients with suspected NAFLD who are anticipating a liver biopsy, or patients with imaging evidence of cirrhosis who have either NAFLD-cirrhosis or cryptogenic cirrhosis by clinical criteria.

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 21 standard drinks on average per week for  men and > 14 standard drinks on average per week for women.
• 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 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.
• Documented history of hepatocellular carcinoma.   
• 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 provide informed consent.