Mortality Related to Nonalcoholic Fatty Liver Disease Is Increasing in the United States

Abstract

Population‐level nonalcoholic fatty liver disease (NAFLD) death rate data are sparse. We described death rates for adults with NAFLD in the United States using mortality data from the National Vital Statistics System multiple‐cause mortality data (2007‐2016). Decedents who had NAFLD were identified by International Classification of Diseases (ICD) codes K75.81, K76.0, K74.0, K74.6, and K76.9. Among NAFLD decedents, cause‐specific deaths (e.g., cardiovascular disease [CVD], cirrhosis, hepatocellular carcinoma [HCC], non‐liver cancer, diabetes mellitus [DM]) were identified by underlying cause of death ICD‐10 codes. Trends were evaluated by average annual percentage change (AAPC) in age‐standardized death rate (ASDR) per 100,000 persons. Among the 25,129,960 decedents aged ≥20 years, 353,234 (1.4%) decedents had NAFLD (212,322 men; 260,765 non‐Hispanic whites, 32,868 non‐Hispanic blacks, 46,530 Hispanics, 5,025 non‐Hispanic American Indian or Alaska Natives [AIANs], 7,023 non‐Hispanic Asian or Pacific Islanders [APIs]), with a mean age at death of 64.47 ± 13.17 years. During the study period, the ASDR for NAFLD increased by 15% (12.94 to 14.90; AAPC, 1.98%; P < 0.001]), while women (AAPC, 2.99% vs. 1.16% men; P = 0.003), non‐Hispanic whites (AAPC, 2.48%), non‐Hispanic AIANs (AAPC, 2.31%), and Hispanics (AAPC, 0.74%) experienced the highest annual increases. Stable trends were noted for non‐Hispanic blacks and non‐Hispanic APIs. Among subgroups, Mexican (AAPC, 1.75%) and Asian Indians (AAPC, 6.94%) experienced annual increases. The top six underlying causes of death (155,894 cirrhosis, 38,444 CVD, 19,466 non‐liver cancer, 10,867 HCC, 8,113 DM, and 5,683 lung disease) accounted for 67.5% of NAFLD‐related deaths. For cause‐specific deaths, ASDR increased for HCC (AAPC, 3.82%), DM (AAPC, 2.23%), non‐liver cancer (AAPC, 2.14%), CVD (AAPC, 1.59%), and cirrhosis (AAPC, 0.96%). Conclusion: NAFLD‐related deaths in U.S. adults are increasing. Cirrhosis is the top cause‐specific death, followed by CVD. Women, non‐Hispanic whites, and non‐Hispanic AIANs (subgroups Mexicans and Asian Indians) experienced the highest increases in deaths. Policies addressing the societal burden of NAFLD are needed.

Have incidence rates of liver cancer peaked in the United States?

“…The prevalence of NAFLD currently is estimated to be approximately 30% in the general US population, and NAFLD, particularly in its most severe form, nonalcoholic steatohepatitis, has become an important risk factor for HCC in many countries, including the United States . However, individuals with NAFLD are more likely to die of cirrhosis, cardiovascular disease, diabetes, and non‐HCC cancer than they are to die of HCC . This suggests that the rising prevalence of NAFLD potentially could decrease the incidence of HCC.…”

The impact of modifiable risk factors on the long‐term outcomes of non‐alcoholic fatty liver disease

“…NAFLD is a complex disease whose pathogenesis is dependent on an underlying genetic predisposition and several environmental factors. Recent data suggest that the global prevalence of NAFLD is rising as a consequence of the pandemic of obesity, insulin resistance and diabetes mellitus, which are common risk factors for both NAFLD and cardiovascular disease (CVD) . Although patients with NAFLD, specifically those with non‐alcoholic steatohepatitis (NASH), are at an increased risk for liver‐related mortality, evidence suggests that CV risk factors are major drivers of morbidity and mortality among patients with NAFLD …”

“…2,[9][10][11] Recent data suggest that the global prevalence of NAFLD is rising as a consequence of the pandemic of obesity, insulin resistance and diabetes mellitus, which are common risk factors for both NAFLD and cardiovascular disease (CVD). 3,[12][13][14] Although patients with NAFLD, specifically those with non-alcoholic steatohepatitis (NASH), are at an increased risk for liver-related mortality, evidence suggests that CV risk factors are major drivers of morbidity and mortality among patients with NAFLD. 10,[15][16][17][18][19] Recently, national efforts for CVD prevention via control of behavioural and biological risk factors have been undertaken.…”

The Natural History of NAFLD, a Community‐Based Study at a Large Health Care Delivery System in the United States

“…Previous studies have suggested that Mexican American ethnicity is associated with a higher risk for NAFLD but not necessarily a higher risk of advanced hepatic fibrosis and cirrhosis. (40)(41)(42) However, a recent study (43) showed increasing rates of NAFLD-related deaths among Mexican Hispanics and Asian Indians. Future studies are needed to clarify possible underlying genetic and environmental factors to explain these findings, and further study of the current data set is ongoing to investigate liver-related versus non-liver-related causes of death.…”