Pulmonary function is associated with fibrosis severity in patients with biopsy‐proven nonalcoholic fatty liver disease

Abstract

Background & Aims The association between nonalcoholic fatty liver disease (NAFLD) and pulmonary function remains elusive because of the heterogeneous spectrum and inaccurate diagnostic methods of NAFLD, and insufficient pulmonary function data. We conducted this study to identify the association between histological severity of NAFLD and pulmonary function. Methods This study included patients ≥18 years old with baseline pulmonary function data between August 2014 and July 2019 within a biopsy‐evaluated prospective NAFLD cohort. Cross‐sectionally, pre‐/post‐bronchodilator spirometric data with diffusing capacity (DLCO) were compared according to histological severity of NAFLD in the various demographic and metabolic subgroups. Multivariable‐adjusted analysis revealed specific histological features associated with reduced pulmonary function. Results In a total of 420 patients with biopsy‐proven NAFLD, pre‐/post‐bronchodilator forced vital capacities (FVCs; a percentage of the predictive value) were inversely correlated with histological severity of NAFLD. Conversely, pre‐bronchodilator forced expiratory volume in 1 second (FEV1)/FVC was positively correlated with NAFLD severity. Post‐bronchodilator FVC (%) decreased and DLCO/alveolar volume (VA) increased linearly with worsening histological severity of NAFLD in multivariable analysis. In particular, fibrosis stage remained a significant independent predictor of decreased post‐bronchodilator FVC (%) (β‐coefficient, 4.41; 95% confidence interval [−8.39, −0.43]; P = .031) even after adjusted for clinical variables, exclusively in age <65 years, female, never‐smoker and nonchronic obstructive pulmonary disease subgroups. Conclusions Pulmonary function deteriorates with worsening histological severity of NAFLD, especially at the fibrosis stage. The common pathogenesis of reduced pulmonary function and NAFLD fibrosis progression should be further explored.

Lipid Metabolism Disorders in the Comorbid Course of Nonalcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease

“…It is interesting that sarcopenia in patients with COPD is associated with an increased risk of NAFLD and more severe fibrosis independent of lung function and metabolic characteristics [ 228 ]. Moreover, worsening histologic severity of NAFLD, especially at the fibrosis stage, is accompanied by decreased lung function [ 229 ].…”

Greater Muscular Strength Is Associated with a Lower Risk of Pulmonary Dysfunction in Individuals with Non-Alcoholic Fatty Liver Disease

“…The positive relationship between NAFLD and pulmonary dysfunction has been well established by different types of observations, including a cross-sectional study using the data from the third National Health and Nutrition Examination Survey (NHANES III) involving 9976 participating adults [ 9 ], meta-analyzing data from five cross-sectional studies and one longitudinal study involving 133,707 individuals [ 30 ], and a prospective study using liver biopsy [ 31 ]. Likewise, the present study observed reduced pulmonary function in the NAFLD cohort.…”

Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline

“…Growing evidence indicates that lung function impairment is related to the presence of NAFLD or the histological severity of NAFLD (i.e., fibrosis severity). 10 Many cross-sectional studies have reported that NAFLD has a significant correlation with lung diseases with obstructive or restrictive physiology. 17 In a recent cohort study, the FEV 1 % of the predicted value was classified into quartiles, and the incidence of NAFLD was higher in the group with a lower quartile of FEV 1 .…”

“… 9 When analyzing histological data from NAFLD patients, the relationship between hepatic steatosis and lung function impairment might be substantially confounded by factors related to metabolic syndrome; however, fibrosis severity was independently associated with FVC impairment. 10 Therefore, the association between lung function impairment and NAFLD may be partly explained by the mechanisms underlying metabolic syndrome or hepatic fibrosis. However, since lung function is a dynamic variable that changes over time, the results of any cross-sectional analysis of the relationship between lung function and NAFLD should be interpreted with caution.…”