Fatty Liver Disease: Diagnostic Challenges and Updates


Non-alcoholic fatty liver disease (NAFLD) indicates evidence of fat in the liver, either by imaging or histology, in a patient without a reason to have secondary fat accumulation (e.g. significant alcohol consumption, use of certain medications, or inherited storage defects, etc). Histologic examination of liver tissue is required to sub-classify NAFLD as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). NAFL represents steatosis without histologic liver injury while NASH represents steatosis with histologic evidence of liver injury (i.e. ballooned hepatocytes, inflammation, and fibrosis).

Non-alcoholic steatohepatitis (NASH) key pathologic features:

  • Steatosis >5%
  • Inflammation (lobular)
  • Hepatocellular injury (ballooned hepatocytes)

The risk of progression to advanced fibrosis in NAFL is minimal while in NASH, progression to cirrhosis and/or development of hepatocellular carcinoma (HCC) is well described. NASH cirrhosis is defined as cirrhosis with current or previous evidence of NAFLD. Risk factors for NASH include metabolic syndrome, dyslipidemia, diabetes mellitus type 2, and obesity. There are no clinical or radiological tests that can reliably diagnose steatohepatitis and serum transaminases often correlate poorly with biopsy findings. Histologic diagnosis remains the gold standard for diagnosis of NASH. It is important to recognize diagnostic pitfalls in evaluating NAFLD biopsies and to appreciate the role of scoring systems used in clinical trials.

Originally presented on February 5, 2018, in Park City, Utah.

Lecture Presenter

Ryan M. Gill, MD, PhD

Ryan M. Gill, MD, PhD

Associate Professor of Clinical Pathology, University of California
San Francisco School of Medicine

Dr. Ryan Gill is a surgical pathologist at UCSF Medical Center who specializes in the diagnosis and evaluation of adult and pediatric liver disease, liver transplantation, inflammatory bowel disease, and liver and gastrointestinal tract neoplasia and lymphoma. In his research, he focuses on diagnosis, prognosis and treatment options for medical liver disease (in particular NASH), liver transplantation, inflammatory bowel disease, liver/GI neoplasia, and extranodal lymphoma. Dr. Gill received an MD and PhD. at the University of Kansas in Kansas City, KS. He then completed a combined anatomic and clinical pathology residency, followed by fellowships in hematopathology and liver and gastrointestinal pathology at UCSF. Dr. Gill is a member of several professional organizations, including the Hans Popper Hepatopathology Society, the Rodger C. Haggitt Gastrointestinal Pathology Society, the Pancreatobiliary Pathology Society, the American Pathology Foundation, and the United States and Canadian Academy of Pathology. Dr. Gill has published numerous book chapters and peer-reviewed articles on liver and gastrointestinal pathology and lectures around the world. He is an Associate Professor, and the Director of Surgical Pathology, in the UCSF Department of Pathology.


After this presentation, participants will be able to:

  • Describe the essential histologic criteria for diagnosis of non-alcoholic steatohepatitis
  • Identify the most common pitfalls in non-alcoholic steatohepatitis diagnosis
  • Define the role of the NAFLD activity score (NAS) in clinical trials

Sponsored by:

University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories