Causes and risk profiles of mortality among individuals with nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. The fibrosis stage is a predictor of all-cause mortality in NAFLD. Mortality in individuals with NAFLD has been steadily increasing, and the most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extrahepatic cancer, liver-related mortality, and diabetes. High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. Achieving weight loss through adherence to a high-quality diet and sufficient physical activity is the most important predictor of improvement in NAFLD severity and the benefit of survival. Given the increasing health burden of NAFLD, future studies with more longterm mortality data may demonstrate an independent association between NAFLD and mortality.

Machine Learning Enables Single-Score Assessment of MASLD Presence and Severity

“…Furthermore, examining disease-specific mortality, each quintile increase resulted in HRs of 1.33 (1.31-1.35) for mortality due to cardiovascular disease, 1.23 (1.20-1.25) for mortality due to diabetes, and 1.22 (1.21-1.24) for mortality due to extrahepatic cancer ( Supplemental Table 22 ), all of which are known common causes of death in MASLD patients. 17 Significant associations for all-cause mortality also present in Bio Me , where each quintile increase in predicted score resulted in HRs of 1.13 (1.08-1.19) among all participants and 1.13 (1.07-1.19) among controls ( Figure 3c-d ; Supplemental Figure 1c-d ).…”

“…16 22), all of which are known common causes of death in MASLD patients. 17 Significant associations for all-cause mortality also present in BioMe, where each quintile increase in predicted score resulted in HRs of 1.13 (1.08-1. 19) among all participants and 1.13 (1.07-1.19) among controls (Figure 3c-d; Supplemental Figure 1c-d).…”

Nonlinear correlation between fatty liver index and carotid intima media thickness among individuals undergoing health examination

“…The leading cause of death in individuals with NAFLD is CVD ( 13 ). A recent meta-analysis reported that NAFLD was associated with a moderately increased risk of fatal or non-fatal CVD events (pooled HR: 1.45, 95% CI: 1.31–1.61).…”

The growing burden of non-alcoholic fatty liver disease on mortality

“…In this issue of Clinical and Molecular Hepatology, Konyn et al have presented the results of an extensive review of the current literature, focusing on the causes and risk profiles of mortality in patients with NAFLD. 5 Based on their findings, the authors have concluded that 1) NAFLD per se may not independently increase the risk of all-cause mortality; 2) the most common causes of death in patients with NAFLD include cardiovascular disease, extrahepatic cancer, liver disease, and diabetes; 3) risk factors for increased mortality in NAFLD are mutation in the patatin like phospholipase domain containing 3 (PNPLA3) gene, low thyroid function, and sarcopenia; and 4) dietary modification and physical activity leading to weight loss have a significant effect on decreasing the mortality.…”

“…In the review by Konyn et al, an emphasis on the impact of diabetes on NAFLD is noteworthy, since mortality among patients with diabetes and chronic liver disease is increasing, while age-standardized mortality due to diabetes is declining. 5 According to the authors' recommendations, clinicians should be cognizant of the bidirectional impact of NAFLD and diabetes. (FibroScan-AST) for detecting significant fibrosis.)…”