Reply:
Authors: Joanne B. Krasnoff, Nathan M. Bass, Patricia L. Painter, Raphael B. Merriman
Journal: Hepatology (2008)

We thank Drs. Manco and Nobili for their interest and thoughtful comments on our article examining the health-related fitness and physical activity participation of patients with a histological spectrum of nonalcoholic fatty liver disease (NAFLD).1 It is noteworthy that they have observed similar findings of significantly reduced capacity to perform physical activity in children with NAFLD compared to obese insulin-resistant children without NAFLD. We applaud the integrated care model they have implemented in their outpatient NAFLD clinic.2, 3 Indeed, a cardiologist attending to cardiovascular comorbidities (for example, hypertension) in persons with NAFLD would enhance patient care. However, participation in physical activity by those patients with reduced exercise capacity does not necessarily require "strict monitoring ensured by a cardiologist". In our study, we performed maximal symptom-limited treadmill testing in 37 individuals with NAFLD without adverse events, despite the fact that most patients manifested several comorbidities. Obviously, appropriate management of comorbidities will clearly reduce the risk of an adverse event during physical activity participation of submaximal exertion. Requiring cardiologist supervision for physical activity participation adds another potentially significant barrier (and expense) for these patients to adopt and maintain a regular exercise program. We certainly agree that our lack of appropriate control groups (nonobese, albeit with abdominal obesity, one with both insulin resistance [IR] and NAFLD and the other with only IR) is a limitation of this study. However, the intent of this initial study was to determine whether objective measures of health-related fitness and physical activity differ with severity of NAFLD. Furthermore, in practice, it would be quite difficult to include such control groups of meaningful size for the following reasons: (1) nonobese patients with IR and NAFLD are relatively uncommon and (2) patients with IR without NAFLD frequently lack histological confirmation.4, 5 Indeed, reduced lean mass, small cross-sectional muscle fiber area, and increased triglyceride deposition in skeletal muscle in conjunction with dysfunctional/reduced lipolysis can result in reduced cardiorespiratory fitness. However, it is unknown whether these adaptations take place as a result of reduced physical activity, NAFLD, or both. We agree entirely that for exercise to be successfully implemented as a therapeutic strategy there is a strong need for individualized exercise prescription. As such, we have recently submitted a manuscript for publication that reviews the evidence for exercise training as a therapy for NAFLD and also presents the principles for prescribing exercise as a therapeutic intervention. Future studies will endeavor to better determine the relative contributions of IR, adiposity, and NAFLD to reduced fitness. Joanne B. Krasnoff Ph.D.*, Nathan M. Bass M.D., Ph.D. , Patricia L. Painter Ph.D. , Raphael B. Merriman M.B.?, * University of California San Francisco, Clinical and Translational Science Institute Clinical Research Center, Exercise Physiology & Body Composition Laboratory, San Francisco, CA, University of California San Francisco, Division of Gastroenterology, San Francisco, CA, University of Minnesota, Division of Renal Diseases and Hypertension, Minneapolis, MN, ? California Pacific Medical Center and Research Institute, Division of Gastroenterology, San Francisco, CA.