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      Nonalcoholic Fatty Liver Disease and Alcoholic Liver Disease are Major Drivers of Liver Mortality in the United States

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          Abstract

          In the United States, chronic viral hepatitis B and C (CHB and CHC), nonalcoholic fatty liver disease (NAFLD), and alcohol‐related liver disease (ALD) are the main causes of liver deaths attributable to hepatocellular carcinoma (HCC) and cirrhosis. Our aim was to assess the changes in the rates of mortality and years of potential life lost (YLL) for HCC and cirrhosis due to different liver diseases. We used multiple‐cause mortality data (2007‐2017) from the National Center for Health Statistics. Annual percentage change (APC) in age‐standardized death rate per 100,000 (ASDR) and age‐standardized years of life lost per 100,000 (ASYLLR) were calculated. In the United States in 2017, there were 2,797,265 deaths with 73,424 liver deaths, contributing to 1,467,742 of YLL. Of the liver deaths, HCC was noted in 12,169 (16.6%) and cirrhosis in 60,111 (82.0%). CHC was responsible for 50.4% of HCC deaths; NAFLD, 35.4%; HBV, 6.0%; ALD, 5.4%; and others, 2.8%. NAFLD was responsible for 48.9% of cirrhosis deaths; ALD, 34.7%; CHC, 12.3%; CHB, 0.9%; and others, 3.2%. Between 2007 and 2017, the increase in ASDR for HCC due to ALD and NAFLD accelerated after 2014 (APC, 11.38% and 6.55%, respectively) whereas CHC stabilized (APC, 0.63%; P = 0.272) after 2011. The increase in ASYLLR of HCC escalated after 2014 for ALD and NAFLD (APC, 12.12% and 6.15%, respectively) and leveled out for CHC after 2012 (APC, −1.05%; P = 0.056). Furthermore, the highest annual increase in ASDR and ASYLLR for cirrhosis was due to ALD (APC, 3.24% and 3.34%, respectively) followed by NAFLD (APC, 1.23% and 0.49%, respectively). Conclusion: Over the past decade, ASDR and ASYLLR due to ALD and NAFLD have been increasing in the United States. The rising burden of HCC and cirrhosis are primarily driven by NAFLD and ALD.

          Abstract

          In the United States (U.S.), chronic viral hepatitis B and C (CHB and CHC), non‐alcoholic fatty liver disease (NAFLD) and alcohol‐related liver disease (ALD) are the main causes of liver deaths attributable to hepatocellular carcinoma (HCC) and cirrhosis.Over the past decade, ASDR and ASYLL are increasing in the U.S. The rising burden of HCC and cirrhosis are primarily driven by NAFLD and ALD.

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          Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study

          Abstract Objective To describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region. Design Observational cohort study. Setting Death certificate data from the Vital Statistics Cooperative, and population data from the US Census Bureau compiled by the Center for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (1999-2016). Participants US residents. Main outcome measure Deaths from cirrhosis and hepatocellular carcinoma, with trends evaluated using joinpoint regression. Results From 1999 to 2016 in the US annual deaths from cirrhosis increased by 65%, to 34 174, while annual deaths from hepatocellular carcinoma doubled to 11 073. Only one subgroup—Asians and Pacific Islanders—experienced an improvement in mortality from hepatocellular carcinoma: the death rate decreased by 2.7% (95% confidence interval 2.2% to 3.3%, P<0.001) per year. Annual increases in cirrhosis related mortality were most pronounced for Native Americans (designated as “American Indians” in the census database) (4.0%, 2.2% to 5.7%, P=0.002). The age adjusted death rate due to hepatocellular carcinoma increased annually by 2.1% (1.9% to 2.3%, P<0.001); deaths due to cirrhosis began increasing in 2009 through 2016 by 3.4% (3.1% to 3.8%, P<0.001). During 2009-16 people aged 25-34 years experienced the highest average annual increase in cirrhosis related mortality (10.5%, 8.9% to 12.2%, P<0.001), driven entirely by alcohol related liver disease. During this period, mortality due to peritonitis and sepsis in the setting of cirrhosis increased substantially, with respective annual increases of 6.1% (3.9% to 8.2%) and 7.1% (6.1% to 8.4%). Only one state, Maryland, showed improvements in mortality (−1.2%, −1.7% to −0.7% per year), while many, concentrated in the south and west, observed disproportionate annual increases: Kentucky 6.8% (5.1% to 8.5%), New Mexico 6.0% (4.1% to 7.9%), Arkansas 5.7% (3.9% to 7.6%), Indiana 5.0% (3.8% to 6.1%), and Alabama 5.0% (3.2% to 6.8%). No state showed improvements in hepatocellular carcinoma related mortality, while Arizona (5.1%, 3.7% to 6.5%) and Kansas (4.3%, 2.8% to 5.8%) experienced the most severe annual increases. Conclusions Mortality due to cirrhosis has been increasing in the US since 2009. Driven by deaths due to alcoholic cirrhosis, people aged 25-34 have experienced the greatest relative increase in mortality. White Americans, Native Americans, and Hispanic Americans experienced the greatest increase in deaths from cirrhosis. Mortality due to cirrhosis is improving in Maryland but worst in Kentucky, New Mexico, and Arkansas. The rapid increase in death rates among young people due to alcohol highlight new challenges for optimal care of patients with preventable liver disease.
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            Epidemiology of chronic liver diseases in the USA in the past three decades

            Given significant advances in treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of liver diseases in the USA may be changing. Our aim was to assess the shift in the prevalence of different liver disease aetiologies in the USA over the past three decades. National Health and Nutrition Examination Surveys (NHANES; cross-sectional 1988–1994 and 1999–2016) were used. A total of 58 731 adults from NHANES (1988–2016) were included. Over the study period, the prevalence of chronic hepatitis B and alcoholic liver disease remained stable: 0.3%–0.4% and 0.8%–1.0%, respectively (p>0.05). The prevalence of chronic hepatitis C decreased nearly twofold: 1.6% in 1988–1994 to 0.9% in 2013–2016 (p=0.03). In contrast, the prevalence of non-alcoholic fatty liver disease (NAFLD; by US-Fatty Liver Index) increased from 20.0% (1988–1994) to 28.3% (1999–2004) to 33.2% (2009–2012) and 31.9% (2013–2016) (p<0.0001). Furthermore, steady increases were observed in the rates of obesity (22.2% in 1988–1994 to 31.0% in 1999–2004 to 38.9% in 2013–2016), type 2 diabetes mellitus (T2DM) (from 7.2% to 8.2% to 13.5% same years), insulin resistance and hypertension (all p<0.0001). Yearly trend analyses showed that the only LD with consistently increasing prevalence was NAFLD (trend p=0.01). Multivariable regression analysis showed that obesity (OR 10.4; 95% CI 9.5 to 11.3) and T2DM (OR 3.7; 95% CI 3.2 to 4.2) were the major independent predictors of NAFLD. Over the past 30 years in the USA, NAFLD is the only liver disease with growing prevalence, synchronous with the increasing rates of obesity and T2DM.
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              Contribution of Alcoholic and Nonalcoholic Fatty Liver Disease to the Burden of Liver-Related Morbidity and Mortality.

              Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. NAFLD is associated with obesity and metabolic syndrome whereas ALD is associated with excessive alcohol consumption. Both diseases can progress to cirrhosis, hepatocellular carcinoma, and liver-related death. A higher proportion of patients with NAFLD die from cardiovascular disorders than patients with ALD, whereas a higher proportion of patients with ALD die from liver disease. NAFLD and ALD each are associated with significant morbidity, impairment to health-related quality of life, and economic costs to society.
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                Author and article information

                Contributors
                zobair.younossi@inova.org
                Journal
                Hepatol Commun
                Hepatol Commun
                10.1002/(ISSN)2471-254X
                HEP4
                Hepatology Communications
                John Wiley and Sons Inc. (Hoboken )
                2471-254X
                04 April 2020
                June 2020
                : 4
                : 6 ( doiID: 10.1002/hep4.v4.6 )
                : 890-903
                Affiliations
                [ 1 ] Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church VA
                [ 2 ] Division of Gastroenterology and Hepatology The Johns Hopkins Hospital Baltimore MD
                [ 3 ] Center for Liver Diseases Department of Medicine Inova Fairfax Medical Campus Falls Church VA
                Author notes
                [*] [* ] Address Correspondence and Reprint Requests to:

                Zobair M. Younossi, M.D., M.P.H.

                Center for Liver Diseases, Department of Medicine, Inova Fairfax Medical Campus

                3300 Gallows Road

                Falls Church, VA 22042

                E‐mail: zobair.younossi@ 123456inova.org

                Tel.: +1‐703‐776‐2540

                Author information
                https://orcid.org/0000-0001-9313-577X
                Article
                HEP41510
                10.1002/hep4.1510
                7262283
                32490324
                3436bca1-d466-468c-94b3-2fd1765c6f39
                © 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

                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
                : 30 August 2019
                : 23 January 2020
                : 01 March 2020
                Page count
                Figures: 3, Tables: 4, Pages: 14, Words: 16840
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:01.06.2020

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