Corey, Kathleen

Background and Aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD. Approach and Results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.

Abstract Background and Aims The NASH Clinical Research Network histologic scoring system, the gold‐standard NASH histology assessment for clinical trials, has demonstrated intrarater and interrater variability. An expert panel in a previous systematic Research and Development/University of California Los Angeles (RAND/UCLA) study determined that existing histologic scoring systems do not fully capture NASH disease activity and fibrosis, and standardized definitions of histologic features are needed. We evaluated the reliability of existing and alternate histologic measures and their correlations with a disease activity visual analog scale to propose optimal components for an expanded NAFLD activity score (NAS). Approach and Results Four liver pathologists who were involved in the prior RAND/UCLA study underwent standardized training and multiple discussions with the goal of improving agreement. They were blinded to clinical information and scored histologic measures twice, ≥2 weeks apart, for 40 liver biopsies representing the full spectrum of NAFLD. Index intraclass correlation coefficient (ICC) estimates demonstrated intrarater (0.80–0.85) and interrater (0.60–0.72) reliability. Hepatocyte ballooning items had similar interrater ICCs (0.68–0.79), including those extending scores from 0–2 to 0–4. Steatosis measures (interrater ICCs, 0.72–0.80) correlated poorly with disease activity. Correlations with disease activity were largest for hepatocyte ballooning and Mallory‐Denk bodies (MDBs), with both used to develop the expanded NAS (intrarater ICC, 0.90; interrater ICC, 0.80). Fibrosis measures had ICCs of 0.70–0.87. Conclusions After extensive preparation among a group of experienced pathologists, we demonstrated improved reliability of multiple existing histologic NAFLD indices and fibrosis staging systems. Hepatocyte ballooning and MDBs most strongly correlated with disease activity and were used for the expanded NAS. Further validation including evaluation of responsiveness is required.