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Clinicians rely upon the severity of liver fibrosis to segregate patients with well‐compensated nonalcoholic fatty liver disease (NAFLD) into subpopulations at high‐ versus low‐risk for eventual liver‐related morbidity and mortality. We compared hepatic gene expression profiles in high‐ and low‐risk NAFLD patients to identify processes that distinguish the two groups and hence might be novel biomarkers or treatment targets. Microarray analysis was used to characterize gene expression in percutaneous liver biopsies from low‐risk, “mild” NAFLD patients (fibrosis stage 0‐1; n = 40) and high‐risk, “severe” NAFLD patients (fibrosis stage 3‐4; n = 32). Findings were validated in a second, independent cohort and confirmed by real‐time polymerase chain reaction and immunohistochemistry (IHC). As a group, patients at risk for bad NAFLD outcomes had significantly worse liver injury and more advanced fibrosis …