Abstract
The purpose of this study was to determine the relation between liver histology, exercise tolerance, and diastolic function in patients with nonalcoholic fatty liver disease (NAFLD). Myocardial remodeling and diastolic dysfunction have been associated with NAFLD. However, its physiological impact and relationship to the histological severity of NAFLD is not known. Cardiopulmonary exercise testing and stress echocardiography was performed in subjects with biopsy-confirmed NAFLD. Maximal aerobic exercise capacity (peak oxygen consumption [VO(2)]) was related to diastolic function (mitral annulus Doppler velocity e' and ratio of early diastolic filling pressure [E] to e' [E/e']) at rest and peak exercise. Autonomic dysfunction was determined from heart rate recovery after exercise. Independent predictors of cardiac function and exercise capacity were identified by multivariable regression. Thirty-six subjects (nonalcoholic fatty liver [NAFL = 15], nonalcoholic steatohepatitis [NASH = 21]) were enrolled. NASH was associated with impaired exercise capacity compared with NAFL (median peak VO(2) 17.0 [15.4, 18.9] vs 19.9 [17.4, 26.0], p = 001); pVO(2) declined with increasing fibrosis (F0 = 22.5, F1 = 19.9, F2 = 19.0, F3 = 16.6 ml·kg(-1)·min(-1); p = 0.01). Similarly, E/e' during exercise increased progressively with increasing fibrosis (F0 = 5.6, F1 = 6.5, F2 = 8.7, F3 = 9.8; P = 0.02). Finally, heart rate recovery, a marker of autonomic function, was blunted in those with higher fibrosis stages (F0 = 25 [20, 30], F1 = 23 [17.5, 27.0], F2 = 17 [11.8, 21.5], F3 = 11 [8.5, 18.0] beats per minute; p <0.01). Fibrosis was an independent predictor of these functional outcomes. In conclusion, NASH is associated with impaired exercise capacity and diastolic dysfunction compared with NAFL. The severity of impairment is directly related to the severity of fibrosis stage in precirrhotic stages of NAFLD.