ABSTRACT
Support is requested for a Keystone Symposia conference entitled Integrated Pathways of Disease in NASH
and NAFLD, organized by Drs. Scott L. Friedman, Arun J. Sanyal, Brent A. Tetri, Mary E. Rinella and
Christopher R. Shepard. The conference will be held in Santa Fe, New Mexico from January 20-24, 2019.
The global prevalence of nonalcoholic fatty liver disease (NAFLD) has risen precipitously over the past two
decades in parallel with the worldwide obesity epidemic, however there are no approved therapies. The more
advanced form of the disease, non-alcoholic steatohepatitis (NASH) is associated with progressive fibrosis and
an increased risk of liver cancer. Despite the growing number of systemic and liver-specific abnormalities
identified in patients with NAFLD, a clear hierarchy of the relative importance of specific defects has not
emerged. Furthermore, a clear understanding of which individuals are at highest risk for progression to
advanced liver disease and cancer remains elusive. Thus, the field lacks an integrated understanding of risk
prediction, pathogenesis, and validated biomarkers to predict or track disease progression without reliance on
liver biopsies. Therefore, the goals of this meeting are to: 1) Explore genetic and ethnic contributions to
NAFLD development; 2) Clarify underlying pathogenic defects in NAFLD and NASH, focusing on the specific
contributions of lipotoxicity, the microbiome, innate immune signaling, and drivers of fibrosis; 3) Highlight
emerging prognostic and diagnostic biomarkers that are yielding new, more streamlined clinical trial designs
that evaluate novel therapies. As a result of this meeting, attendees will gain a more holistic understanding of
the unmet needs and new paths to advancing our understanding of NAFLD pathogenesis, diagnosis and
therapy. The multidisciplinary nature of the topics and speakers promises to generate novel insights that
represent convergent expertise and opinion. In doing so, new paradigms are likely to emerge that greatly
inform the expanding number of emerging diagnostic markers and therapeutic agents. The meeting comes at
a propitious time at which there is already sufficient basic translational and clinical research to extract
important new insights, focus on unmet needs and refine research strategies for the future.