Nonalcoholic fatty liver disease (NAFLD) affects 10%-30% of the general U.S. population and can progress to significant fibrosis and cirrhosis. When nonalcoholic steatohepatitis (NASH) is present, the 5-year and 10-year survivals are estimated at 67% and 59%, respectively. The presence of NASH and early fibrosis is currently established only by liver biopsy; noninvasively determining who has NASH and who is at risk for progressing to cirrhosis 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. To meet these goals, patients with the full spectrum of NAFLD or cryptogenic cirrhosis were enrolled in an observational Database study.

Comprehensive data, including demographics, medical history, symptoms, medication use, diet and exercise habits, and routine laboratory studies were collected on all patients at entry and at annual visits for up to 4 years after enrollment. Study questionnaires administered at enrollment and at selected follow-up visits included AUDIT; Block Food Questionnaire; Skinner Lifetime Drinking History, Physical Activity Questionnaire, Modifiable Activity Questionnaire; and the MOS 36-Item Short-Form Health Survey. Specimens were collected at selected time points during follow-up. If liver biopsies were obtained as part of routine patient care, they were scored using the NASH CRN NAFLD Activity Score (NAS) and fibrosis score.

To determine the associations of readily available demographic, clinical, and laboratory variables with the diagnosis of NASH and its key histological features, and determine the ability of these variables to predict the severity of NAFLD.

• Diagnosis of definite NASH
• Stage of fibrosis
• Grade of inflammation
• Presence of hepatocellular ballooning injury

Patients 18 years or older had to meet any of the following criteria:

• A histologic diagnosis of NAFLD
• A histologic diagnosis of cryptogenic cirrhosis
• Suspected NAFLD based on imaging studies
• Clinical evidence of cryptogenic cirrhosis

Exclusion criteria:

• Clinical or histological evidence of alcoholic liver disease or alcohol consumption during the two years before entry (> 20g/day for men, >10g/day women)
• Evidence of other forms of chronic liver disease
• History of total parenteral nutrition
• Biliopancreatic diversion or bariatric surgery
• Short bowel syndrome
• Suspected or confirmed hepatocellular carcinoma
• Positive for HIV

Readily available clinical and laboratory variables can predict advanced fibrosis in adults with NAFLD, but additional information is needed to reliably predict the presence and severity of NASH.