The Impact of Modifiable Risk Factors on the Long-term Outcomes of Non-alcoholic Fatty Liver Disease

James M. Paik; Rati Deshpande; Pegah Golabi; Issah Younossi; Linda Henry; Zobair M. Younossi


Aliment Pharmacol Ther. 2020;51(2):291-304. 

In This Article

Abstract and Introduction


Background: Cardiovascular (CV) disease is the leading cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD). The American Heart Association (AHA) developed 7 CV health metrics (poor, intermediate and ideal health) to improve CV health.

Aim: To assess population-attributable fractions (PAFs) of CV health metrics to all-cause and CV mortality among NAFLD patients

Methods: We included adult participants from National Health and Nutrition Examination Survey (NHANES 1988–1994) with clinical and mortality data. NAFLD was defined as the presence of hepatic steatosis on ultrasonography in the absence of other chronic liver diseases and excessive alcohol use.

Results: A total of 4040 adults with NAFLD and 7515 without were included. NAFLD had fewer ideal health metrics than non-NAFLD (age-standardised prevalence: 20% vs 10% for ≤1 ideal health metric; 5.1% vs 8.7% for ≥6, all P < .001). Following median follow-up of 19.2 years (IQR: 17.5–21.0 years), 1,136 NAFLD subjects (327 CV deaths) and 1600 non-NAFLD subjects (447 CV deaths) died. Increased number of ideal health metrics (all trend P < .0001) correlated with lower risk for all-cause and CV mortality. If all NAFLD subjects achieved 7 ideal health metrics, 66% of all-cause deaths and 83% of CV deaths were preventable. Among NAFLD subjects, lack of glycaemic control (adjusted PAF = 28.3% all-cause; 38.1% CV) and hypertension (adjusted PAF of 23% all-cause; 52.8% CV) were the largest mortality contributors. Ideal physical activity level obtainment provided an adjusted PAF = 13.9% all-cause and 13.8% CV mortality.

Conclusions: Attainment of ideal CV health metrics provides protection against all-cause and CV deaths in NAFLD.


Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease with increasing prevalence worldwide.[1–8] NAFLD is a complex disease whose pathogenesis is dependent on an underlying genetic predisposition and several environmental factors.[2,9–11] 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).[3,12–14] 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.[10,15–19]

Recently, national efforts for CVD prevention via control of behavioural and biological risk factors have been undertaken. The American Heart Association (AHA) recently developed the CV health metrics (the Simple 7). The Simple 7 is a set of seven modifiable CVD risk factors, four of which are related to health behaviours (body mass, smoking, physical activity and diet) and three related to health factors (blood pressure, cholesterol and glycaemic). The goal of the Simple 7 is to obtain an 'ideal' status for each of these risk factors through prevention interventions and treatments. The associated outcomes are an improvement in CVD health by 20% while reducing stroke and CVD deaths by 20% known as AHA's 2020 goal".[20] The inverse relationship between ideal health metrics and long-term outcomes among the general population is well documented,[21,22] but the evidence assessing this relationship among NAFLD subjects is lacking. Due to the close association of CVD with NAFLD, the CV health metrics' assessment can be applied to patients with NAFLD as a potential guide for interventions that can affect both cardiac and liver outcomes. Therefore, we used a nationally representative sample of the US adults to assess the impact of CV health metrics (Life's Simple 7) on the long-term outcomes of subjects with NAFLD.