Gut Liver.  2023 Jan;17(1):139-149. 10.5009/gnl210545.

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

• Lee HW
• Chung GE
• Koo BK
• Sim H
• Choi M
• Lee DH
• Choi SH
• Kwak SH
• Kim DK
• Kim W
• on behalf of the Innovative Target Exploration of NAFLD (ITEN) consortium

• KMID: 2538165
• DOI: http://doi.org/10.5009/gnl210545

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 func-tion 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 (FEV ₁ ) 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 FEV ₁ (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 FEV ₁(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.

Keyword

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