Smoking Increases the Risk of Hepatocellular Carcinoma and Cardiovascular Disease in Patients with Metabolic-Associated Fatty Liver Disease

The association of smoking with hepatocellular carcinoma (HCC) or cardiovascular disease (CVD) has been reported, but the study of its relationship with metabolic-associated fatty liver disease (MAFLD) is limited. We aimed to investigate the effect of smoking on the incidence of HCC or CVD in MAFLD patients. Using the Korean nationwide health screening database, we analyzed subjects between 2001 and 2015. A total of 283,088 subjects including 110,863 MAFLD patients and 172,225 controls were analyzed. Smoking status was divided by non-smoker, ex-smoker, or current smoker. In the follow-up period, a total of 2903 (1.0%) subjects developed HCC, and the MAFLD group (1723, 1.6%) had a significantly higher incidence than the control group (1180, 0.7%). In the MAFLD group, current smokers showed significantly higher risk of HCC compared to non-smokers (adjusted HR 1.24, 95% CI 1.08–1.41), whereas the control group did not (adjusted HR 1.07, 95% CI 0.89–1.30). A total of 18,984 (6.7%) patients developed CVD, and the incidence was significantly higher in the MAFLD group (8688, 7.8%) than in the control group (10,296, 6.0%), similar to HCC. The risk of CVD in current smokers increased by 22% compared to non-smokers in the MAFLD group (adjusted HR 1.22, 95% CI 1.15–1.30) and by 21% (adjusted HR 1.21, 95% CI 1.13–1.29) in the control group. Based on sex stratification, men showed increased incidence of both HCC and CVD by smoking, whereas women had only increased risk of CVD. Smoking significantly increases the incidence of HCC and CVD in MAFLD patients; thus, it is highly recommended to quit smoking completely in the population with MAFLD.