Gut Liver. 2023;17(1):139-149.

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

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제1저자 이현우, 정고은 · 교신저자 김덕겸, 김원

PMID 35611668 PMC9840916 DOI 10.5009/gnl210545 IF 4.1 소화기내과

소속 (7)

Division of Respiratory and Critical Care, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
Division of Endocrinology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
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 progressionGenome-wide association studyLongitudinal studyNon-alcoholic fatty liver diseasePulmonary function test

Figures

**Fig. 1** Flow diagram for inclusion and classification based on the change in fatty liver status.

**Fig. 2** Annual lung function decline rates (A) and proportion of accelerated lung function decline (B) according to different sonographic changes in fatty liver status. FVC, forced vital capacity; FEV1, forced expiratory volume measured in the first second of exhalation. *p<0.05, ^†p<0.01, ^‡p<0.001.

**Fig. 3** Two-by-two table based on the lung function (A: FVC, B: FEV1) decline rate and the change in fatty liver status. The included subjects were classified according to two different dichotomous variables: slow versus accelerated lung function decline groups and “improved” or “normal” versus “worsened” or “persistent” steatosis groups. FVC, forced vital capacity; FEV1, forced expiratory volume measured in the first second of exhalation; Q1, 1st quartile; Q2, 2nd quartile; Q3, 3rd quartile; Q4, 4th quartile.

**Fig. 4** Manhattan plot of the lung function decline rate and the change in fatty liver status. (A) Manhattan plot of the accelerated forced vital capacity (FVC) decline rate: population with a slow decline rate and improved or normal steatosis (control) versus population with an accelerated decline rate and worsened or persistent steatosis. (B) Manhattan plot of accelerated forced expiratory volume measured in the first second of exhalation (FEV1) decline rate: population with slow decline rate and improved or normal steatosis (control) versus population with an accelerated decline rate and worsened or persistent steatosis.

**Fig. 5** Regional linkage disequilibrium between two newly identified SNPs (rs2294433 and rs12483959) and rs738409 in *PNPLA3* gene associated with nonalcoholic fatty liver disease. Statistical significance is marked by a horizontal line.

그림 출처: PubMed Central 공개 논문 (PMC9840916)

Conflict of interest statement

CONFLICTS OF INTEREST . No potential conflict of interest relevant to this article was reported.

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