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

Hyun Woo Lee; Goh Eun Chung; Bo Kyung Koo; Hyungtai Sim; Murim Choi; Dong Hyeon Lee; Seung Ho Choi; Soo Heon Kwak; Deog Kyeom Kim; Won Kim; Innovative Target Exploration of NAFLD (ITEN) consortium

doi:10.5009/gnl210545

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

Gut Liver. 2023 Jan 15;17(1):139-149. doi: 10.5009/gnl210545. Epub 2022 May 25.

Authors

Affiliations

¹ Division of Respiratory and Critical Care, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
² Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
³ Division of Endocrinology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
⁴ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
⁶ Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
⁷ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Background/aims: A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear.

Methods: This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung function decline rates were classified as "slow" and "accelerated" and compared among four different sonographic changes in steatosis status: "normal," "improved," "worsened," and "persistent." A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function.

Results: Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEV₁) were higher in the worsened/persistent steatosis group than in the normal/improved steatosis group. In multivariable analysis, persistent or worsened status of fatty liver was significantly associated with accelerated declines in FVC (persistent status, odds ratio [OR]=1.22, 95% confidence interval [CI]=1.04-1.44; worsened status, OR=1.30, 95% CI=1.12-1.50), while improved status of fatty liver was significantly associated with slow declines in FEV₁ (OR=0.77, 95% CI=0.64-0.92). The PNPLA3 risk gene was most strongly associated with steatosis status change and accelerated declines in FVC (rs12483959, p=2.61×10^-7) and FEV₁ (rs2294433, p=3.69×10^-8).

Conclusions: Regression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.

Keywords: Disease progression; Genome-wide association study; Longitudinal study; Non-alcoholic fatty liver disease; Pulmonary function test.

MeSH terms

Forced Expiratory Volume
Genome-Wide Association Study
Humans
Lung* / diagnostic imaging
Non-alcoholic Fatty Liver Disease* / genetics
Vital Capacity