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NASH: Nonalcoholic Fatty Liver Disease Incidence and Impact on Metabolic Burden and Death: a 20 Year-Community Study - New trends on obesity and NAFLD in Asia / Lean-NASH
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Download the PDF here
Download the PDF here
"NAFLD is an independent risk factor for
death, but impact decreases with the increase of incident metabolic comorbidities. The lifespan
of NAFLD subjects is 4 years shorter than that of controls, and the majority of the remaining
years are spent in states of metabolic comorbidities.NAFLD incidence increased 5-fold, from 62 to 329/100,000 person-years.The increase was highest (7-fold) in young adults, age 18-39 years.
The 10-year mortality was higher in NAFLD subjects(10.2%) than controls (7.6%). .....arising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25 kg/m2are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD"
Nonalcoholic Fatty Liver Disease Incidence and Impact on Metabolic Burden and Death: a 20 Year-Community Study
Hepatology Sept 23 2017 - Alina M. Allen, MD1, Terry M. Therneau, PhD2, Joseph J. Larson2, Alexandra Coward1, VirendK. Somers, MD, PhD3, Patrick S. Kamath, MD1
1Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
2Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
3Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
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 US community, and the impact of NAFLD on incident metabolic comorbidities (MC), cardiovascular (CV) events and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, MN between 1997-2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate was calculated. The impact of NAFLD on incident MC, CV events and mortality was studied using a multi-state model, with a 4:1 age and sex-matched general population as reference.
We identified 3,869 NAFLD subjects (median age 53, 52% women) and 15,209 controls; median follow-up was 7 (1 to 20) years. NAFLD incidence increased 5-fold, from 62 to 329/100,000 person-years. The increase was highest (7-fold) in young adults, age 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 MC and death.
Mortality risk decreased as the number of incident MC increased: RR= 2.16 (95% 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 MC were present, respectively. The NAFLD impact on CV events was significant only in subjects without MC (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: The 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.
The prevalence of obesity (BMI ³ 30 kg/m2) in the community increasedfrom 28% in 1997 to 37% in 2014. The prevalence of obesity among NAFLD subjects remainedconstant, at 68% during the study period.
Supplementary Figure 3 shows that BMI in thegeneral population has increased from 27.8 to 28.9 kg/m2. Similarly, the BMI in NAFLD subjectsat the time of diagnosis increased from 32.6 kg/m2in 1997 to 34.2 kg/m2 in 2008 when itstabilized.
The mean (± SD) age at the time of NAFLD diagnosis did not change significantly during thestudy period: 55 (± 16) years in 1997 versus 54 (±14) years in 2014. However, the proportion ofNAFLD subjects with 2 or more dysmetabolic comorbidities present at the time of diagnosisincreased over the study period from 21% to 53% (Figure 3).
At the index diagnosis, NAFLD subjects were more likely to have a history of cardiovascular(CV) events than the matched controls (28% vs 18%). At 10 years of follow-up 34% of NAFLDsubjects and 22% of controls had CV events.
Figure 4 shows the impact of NAFLD on incident metabolic
comorbidities after NAFLD diagnosis and mortality in reference to age and sex-matchedcontrols. In this multistate model, NAFLD subjects and their age- and sex- matchedcounterparts are followed as they transition unidirectionally towards death, directly or through
intermediate states of progressive dysmetabolic burden. The dysmetabolic burden wasquantified as one, two or three of the following comorbidities: diabetes, hypertension ordyslipidemia. Compared to controls, NAFLD subjects had a higher risk of developing incidentdysmetabolic comorbidities. The impact of NAFLD is highest on the transition from zero to onemetabolic comorbidity. For example, a subject with NAFLD without DM, HTN or dyslipidemia,was over twice (RR=2.62, 95% CI=2.31-2.96) more likely to develop one or more of thesecomorbidities than an age- and sex- matched control. A subject with NAFLD and either 1 of 3comorbidities (DM, HTN or dyslipidemia), had a 1.67-fold higher risk (RR=1.67, 95% CI=1.51-1.85) of developing additional dysmetabolic comorbidities than an age- and sex- matchedcontrol with one comorbidity but without NAFLD. The impact of NAFLD was lower on thetransition from a state of 2 to 3 metabolic comorbidities (RR=1.62, 95% CI=1.42-1.83). Whenstratified by cirrhosis status, the impact of NAFLD on incident metabolic comorbiditiesdecreased with higher metabolic burden in a similar fashion: RR=2.60, 95% CI 2.30-2.95 totransition from 0 to 1+, RR= 1.66, 95% CI 1.49-1.84 to transition from 1 to 2+, and RR=1.53,95% CI 1.34-1.74 to transition from 2 to 3 metabolic comorbidities.
As seen in Figure 4, NAFLD is an independent risk factor for death, but itsimpact decreases with the number of dysmetabolic conditions. A subject with NAFLD and nometabolic comorbidities has a 2-fold increased mortality risk compared to an age and sexmatchedcontrol with no metabolic comorbidities or NAFLD (RR=2.16, 95% CI=1.41-3.31).
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New trends on obesity and NAFLD in Asia / Lean-NASH
Jnl of Hepatology March 2017
Summary
Traditionally, obesity and its related diseases have been considered a problem in Western countries. However, in the past two decades, urbanisation in many Asian countries has led to a sedentary lifestyle and overnutrition, setting the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, like many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon,arising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25 kg/m2are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD.Although this condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized.Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition, such as thePNPLA3polymorphism appears to be more important in the development of NAFLD in the non-obese population.Lifestyle modificationremains the cornerstone of management for obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While pharmacological agents have entered phase III development for steatohepatitis, Asian patients are under-represented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia.
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