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      Attributable Fractions of Nonalcoholic Fatty Liver Disease for Mortality in the United States: Results From the Third National Health and Nutrition Examination Survey With 27 Years of Follow‐up

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          Abstract

          Background and Aims

          Nonalcoholic fatty liver disease (NAFLD) encompasses a range of conditions, from simple steatosis to nonalcoholic steatohepatitis. Studies in the United States have reported an increased mortality risk among individuals with NAFLD; therefore, the population attributable fractions (PAFs) for mortality were examined.

          Approach and Results

          A total of 12,253 adult individuals with ultrasound assessment of NAFLD from the Third National Health and Nutrition Examination Survey and mortality follow‐up through 2015 were included in the analysis. Cox proportional hazard regression was used to estimate multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD in association with all‐cause and cause‐specific mortality. Overall, sex‐ and race/ethnicity‐specific PAFs and 95% CIs were estimated. In the current study, presence of NAFLD was associated with a 20% increased risk of all‐cause mortality (HR, 1.20; 95% CI, 1.08, 1.34). The overall PAF for all‐cause mortality associated with NAFLD was 7.5% (95% CI, 3.0, 12.0). The PAF for diabetes‐specific mortality was 38.0% (95% CI, 13.1, 63.0) overall, 40.8% (95% CI, 2.1, 79.6) in men, and 36.8% (95% CI, 6.6, 67.0) in women. The PAF for liver disease (LD)‐specific mortality was notably higher in men (68.3%; 95% CI, 36.3, 100.0) than women (3.5%; 95% CI, −39.7, 46.8). In the race‐specific analysis, the PAFs of NAFLD for all‐cause mortality (9.3%; 95% CI, 4.0, 14.6) and diabetes‐specific mortality (44.4%; 95% CI, 10.8, 78.0) were significantly greater than zero only for whites.

          Conclusions

          In the United States, approximately 8% of all‐cause mortality and more than one‐third of LD‐ and diabetes‐specific deaths are associated with NAFLD. With these high percentages, efforts are needed to reduce the burden of NAFLD in the United States.

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          Most cited references22

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          Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics

          The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis (SS), but also with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. As a consequence, apart from increasing all-cause mortality, obesity seems to increase liver-specific mortality in NAFLD patients. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management. As the first step, lifestyle modification (diet and exercise) is recommended, although it is difficult to achieve and sustain. When the first step fails, adding pharmacotherapy is recommended. Several anti-obesity medications have been investigated in NAFLD (e.g., orlistat, glucagon-like peptide-1 analogs), other anti-obesity medications have not been investigated (e.g., lorcaserin, phentermine hydrochloric, phentermine/topiramate and naltrexone/bupropion), whereas some medications with weight-lowering efficacy have not been approved for obesity (e.g., sodium-glucose cotransporter-2 inhibitors, farnesoid X receptor ligands). If the combination of lifestyle modification and pharmacotherapy also fails, then bariatric surgery should be considered in selected morbidly obese individuals. This review summarizes best evidence linking obesity with NAFLD and presents related therapeutic options.
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            The natural history of nonalcoholic fatty liver disease: a population-based cohort study.

            The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.
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              Past, present and future perspectives in nonalcoholic fatty liver disease

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                Author and article information

                Contributors
                christian.alvarez@nih.gov
                Journal
                Hepatology
                Hepatology
                10.1002/(ISSN)1527-3350
                HEP
                Hepatology (Baltimore, Md.)
                John Wiley and Sons Inc. (Hoboken )
                0270-9139
                1527-3350
                25 August 2020
                August 2020
                : 72
                : 2 ( doiID: 10.1002/hep.v72.2 )
                : 430-440
                Affiliations
                [ 1 ] Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville MD
                [ 2 ] Slone Epidemiology Center Boston University Boston MA
                Author notes
                [*] [* ] Address Correspondence and Reprint Requests to:

                Christian S. Alvarez, Ph.D.

                Division of Cancer Epidemiology and Genetics, National Cancer Institute, Shady Grove

                9609 Medical Drive, Room 6E416

                Rockville, MD 20850

                E‐mail: christian.alvarez@ 123456nih.gov

                Tel.: +1‐240‐276‐7981

                Author information
                https://orcid.org/0000-0002-5338-0444
                Article
                HEP31040
                10.1002/hep.31040
                7496113
                31733165
                c8ba11b7-46a7-4aa4-ab2b-7c9a8b1380c6
                Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 27 June 2019
                : 13 November 2019
                Page count
                Figures: 1, Tables: 5, Pages: 15, Words: 16051
                Funding
                Funded by: The National Institutes of Health Intramural Research Program
                Categories
                Original Article
                Original Articles
                Steatohepatitis/Metabolic Liver Disease
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.0 mode:remove_FC converted:11.09.2020

                Gastroenterology & Hepatology
                Gastroenterology & Hepatology

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