Decreased lung function is associated with risk of developing non-alcoholic fatty liver disease: A longitudinal cohort study

Abstract

Background: Decreased lung function is associated with non-alcoholic fatty liver disease (NAFLD), based on linking mechanisms such as insulin resistance and systemic inflammation However, its association with the risk of developing NAFLD is unclear. Our aim was to investigate whether baseline lung function is associated with incident NAFLD in middle-aged healthy Koreans.

Methods: A cohort study of 96,104 subjects (mean age: 35.7 years) without NAFLD were followed up from 2002 to 2015. NAFLD was diagnosed by ultrasound after the exclusion of other possible causes of liver diseases. Baseline percent predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) were categorized in quartiles. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) (using the highest quartile as reference) were calculated for incident NAFLD at follow-up, controlling for covariates and potential confounders.

Results: During 579,714.5 person-years of follow-up, 24,450 participants developed NAFLD (incidence rate, 42.2 per 1,000 person-years). The mean follow-up period was 5.9±3.4 years. Regardless of smoking history, the risk for incident NAFLD increased with decreasing quartiles of FEV1 (%) and FVC (%) in a dose-response manner (p for trend<0.001). In never smokers, the aHRs (95% CIs) for incident NAFLD were 1.15 (1.08-1.21), 1.11 (1.05-1.18), and 1.08 (1.02-1.14) in quartiles 1-3 for FEV1 (%) and 1.12 (1.06-1.18), 1.11 (1.05-1.18), and 1.09 (1.03-1.15) in quartiles 1-3 for FVC (%), compared with the highest quartile reference. Similar inverse association was present in smoke-exposed subjects (aHR for incident NAFLD were 1.14, 1.21, 1.13 and 1.17, 1.11, 1.09 across FEV1(%) and FVC(%) quartile in increasing order, respectively).

Conclusions: Reduced lung function was a risk factor for incident NAFLD in a large middle-aged Korean cohort with over half a million person-years of follow-up.

Fig 1. Flow chart of study participants.

Fig 2. Multivariable-adjusted hazard ratios for incident nonalcoholic fatty liver disease according to quartile of lung function.

Smoke-exposed subjects (A,C) and never smokers (B,D) were dived into quartiles according to baseline precentage of predcited values (% predicted) for FEV1 or FVC. Rregardless of smoking status, adjusted hazard ratios for incident NAFLD increased with decreasing quartiles of FEV1 (%) (A,B) and FVC (%) (C,D) in a dose-response manner (p for trend<0.001). The reference values was set at the highest quartile of FEV1(%) and FVC(%). Models was adjusted for potential covariates and metabolic laboratory markers including age, sex, BMI, alcohol intake, smoking, exercise, education level, center, year of test. aHR, adjusted hazard ratio; FEV1, forced expiratory volume in 1s; FVC, forced vital capacity; NAFLD, nonalcoholic fatty liver disease.