Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study

Abstract

Recent population-based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general, and incidence in particular, are lacking. We examined trends in NAFLD incidence in a U.S. community and the impact of NAFLD on incident metabolic comorbidities (MCs), cardiovascular (CV) events, and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate were calculated. The impact of NAFLD on incident MCs, CV events, and mortality was studied using a multistate model, with a 4:1 age- and sex-matched general population as a reference. We identified 3,869 NAFLD subjects (median age, 53; 52% women) and 15,209 controls; median follow-up was 7 (1-20) years. NAFLD incidence increased 5-fold, from 62 to 329 in 100,000 person-years. The increase was highest (7-fold) in young adults, aged 18-39 years. The 10-year mortality was higher in NAFLD subjects (10.2%) than controls (7.6%; P < 0.0001). NAFLD was an independent risk factor for incident MCs and death. Mortality risk decreased as the number of incident MCs increased: relative risk (RR) = 2.16 (95% confidence [CI], 1.41-3.31), 1.99 (95% CI, 1.48-2.66), 1.75 (95% CI, 1.42-2.14), and 1.08 (95% CI, 0.89-1.30) when 0, 1, 2, or 3 MCs were present, respectively. The NAFLD impact on CV events was significant only in subjects without MCs (RR = 1.96; 95% CI = 1.35-2.86). NAFLD reduced life expectancy by 4 years, with more time spent in high metabolic burden.

Conclusion: Incidence of NAFLD diagnosis in the community has increased 5-fold, particularly in young adults. NAFLD is a consequence, but also a precursor of MC. Incident MC attenuates the impact of NAFLD on death and annuls its impact on CV disease. (Hepatology 2018;67:1726-1736).

Figure 1

Identification of nonalcoholic fatty liver disease cases in Rochester Epidemiology Project Database, using Hospital International Classification of Diseases Adapted (HICDA) codes, a system developed at Mayo for research diagnosis coding, and International Classification of Diseases (ICD)-9 codes.

Figure 2

A. The age and sex-adjusted incidence of NAFLD diagnosis in Olmsted County, Minnesota increased 5-fold, from 62/100,000 person-years in 1997 to 329/100,000 person-years in 2014. B. Incidence of NAFLD diagnosis by age groups. NAFLD incidence increased 7-fold among subjects 18–39 years, 6-fold among subjects 40–59 years and 4-fold among subjects over 60 years. Y-axis represents number of subjects per 100,000 person-years.

Figure 2

A. The age and sex-adjusted incidence of NAFLD diagnosis in Olmsted County, Minnesota increased 5-fold, from 62/100,000 person-years in 1997 to 329/100,000 person-years in 2014. B. Incidence of NAFLD diagnosis by age groups. NAFLD incidence increased 7-fold among subjects 18–39 years, 6-fold among subjects 40–59 years and 4-fold among subjects over 60 years. Y-axis represents number of subjects per 100,000 person-years.

Figure 3

Proportion of NAFLD subjects with one, two or three metabolic comorbidities (diabetes mellitus, hypertension or dyslipidemia) present at the time of diagnosis. The proportion of subjects with multiple comorbidities at NAFLD diagnosis has increased since 1997.

Figure 4

The impact of NAFLD on incident metabolic comorbidities and mortality in reference to age- and sex-matched controls. In this multistate model, NAFLD subjects and their age- and sex-matched counterparts are followed longitudinally as they transition unidirectionally towards death, directly or through intermediate states of progressive dysmetabolic burden. The relative risk of NAFLD subjects (using controls as reference) of transitioning from one state to another is illustrated in the arrows. Compared to controls, NAFLD subjects have a higher risk to develop incident dysmetabolic comorbidities (top row, horizontal arrows). The impact of NAFLD on mortality decreases as the number of dysmetabolic conditions increases (bottom row, vertical arrows).

Figure 5

The time-in-state analysis illustrates the number of years spent in each of the four states of zero, one, two or three comorbidities (diabetes mellitus, hypertension and dyslipidemia) until death by NAFLD subjects and matched controls from the general population. The modelling was performed on NAFLD subjects age 50 and compared to their age- and sex-matched controls. The age of 50 was arbitrarily chosen as it is close to the median age in this cohort. Subjects and controls are followed longitudinally from age 50 to death, as they transition through intermediate states of comorbidities (progressively darker grey areas). The numbers in each box represent the number of years spent in each state. Compared to controls, NAFLD subjects develop higher dysmetabolic states sooner and spend proportionally more or their remaining time in states of metabolic comorbidities. The mean lifetime of NAFLD subjects is 4 years shorter than controls, in both males and females.