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      Trends in Characteristics, Mortality, and Other Outcomes of Patients With Newly Diagnosed Cirrhosis

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          Key Points

          Question

          What are contemporary trends in the characteristics and outcomes of patients with newly diagnosed cirrhosis?

          Findings

          In this cohort study of 9261 patients with newly diagnosed cirrhosis from 2004 to 2014, the proportions of patients younger than 40 years and those 65 years and older increased significantly, as did the proportions with alcoholic cirrhosis and nonalcoholic steatohepatitis. Mortality decreased over time.

          Meaning

          The population of patients with newly diagnosed cirrhosis is facing changes in demographic characteristics, clinical features, and outcomes that may affect future care.

          Abstract

          This cohort study examines changes in the demographic and clinical characteristics and outcomes of patients with newly diagnosed cirrhosis.

          Abstract

          Importance

          Changes in the characteristics of patients with cirrhosis are likely to affect future outcomes and are important to understand in planning for the care of this population.

          Objective

          To identify changes in demographic and clinical characteristics and outcomes in patients with newly diagnosed cirrhosis.

          Design, Setting, and Participants

          A retrospective cohort study of patients with a new diagnosis of cirrhosis was conducted using the Indiana Network for Patient Care, a large statewide regional health information exchange, between 2004 and 2014. Patients with at least 1 year of continuous follow-up before the cirrhosis diagnosis were followed up through August 1, 2015. The analysis was conducted from December 2018 to January 2019.

          Exposures

          Age, cause of cirrhosis, and year of diagnosis.

          Main Outcomes and Measures

          Overall rates for mortality, liver transplant, hepatocellular carcinoma, and hepatic decompensation (composite of ascites, hepatic encephalopathy, or variceal bleeding).

          Results

          A total of 9261 patients with newly diagnosed cirrhosis were identified (mean [SD] age, 57.9 [12.6] years; 5109 [55.2%] male). A 69% increase in new diagnoses occurred over the course of the study period (620 in 2004 vs 1045 in 2014). The proportion of those younger than 40 years increased by 0.20% per year (95% CI, 0.04% to 0.36%; P for trend = .02), and the proportion of those aged 65 years and older increased by 0.81% per year (95% CI, 0.51% to 1.11%; P for trend < .001). The proportion of patients with alcoholic cirrhosis increased by 0.80% per year (95% CI, 0.49% to 1.12%), and the proportion with nonalcoholic steatohepatitis increased by 0.59% per year (95% CI, 0.30% to 0.87%), whereas the proportion with viral hepatitis decreased by 1.36% per year (95% CI, −1.68% to −1.03%) ( P < .001 for all). In patients younger than 40 years, 40 to 64 years, and 65 years and older, mortality rates were 6.4 (95% CI, 5.4 to 7.6), 9.9 (95% CI, 9.5 to 10.4), and 16.2 (95% CI, 15.2 to 17.2) per 100 person-years, respectively ( P < .001). Mortality rates decreased during the study period (11.9 [95% CI, 10.7-13.1] per 100 person-years in 2004 vs 10.0 [95% CI, 8.1-12.2] per 100 person-years in 2014; annual adjusted hazard ratio, 0.87 [95% CI, 0.86 to 0.88]) and were lower in those with alcoholic cirrhosis compared with patients with viral hepatitis (adjusted hazard ratio, 0.89 [95% CI, 0.80 to 0.98]). Rates of hepatocellular carcinoma were low in patients younger than 40 years (0.5 [95% CI, 0.2 to 0.9] per 100 person-years). Liver transplant rates were low throughout the study period (0.3 [95% CI, 0.3-0.4] per 100 person-years). In patients with compensated cirrhosis, rates of hepatic decompensation were lower in patients younger than 40 years (adjusted subhazard ratio 0.78; 95% CI, 0.62 to 0.99) and in patients with nonalcoholic steatohepatitis (adjusted subhazard ratio, 0.51; 95% CI, 0.43 to 0.60).

          Conclusions and Relevance

          The population of patients with newly diagnosed cirrhosis in Indiana has experienced changes in the age distribution and cause of cirrhosis, with decreasing mortality rates. These findings support investment in the prevention and treatment of alcoholic liver disease and nonalcoholic steatohepatitis, particularly in younger and older patients. Additional study is needed to identify the reasons for decreasing mortality rates.

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          Most cited references24

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          Prevalence of 12-Month Alcohol Use, High-Risk Drinking, and DSM-IV Alcohol Use Disorder in the United States, 2001-2002 to 2012-2013

          Lack of current and comprehensive trend data derived from a uniform, reliable, and valid source on alcohol use, high-risk drinking, and DSM-IV alcohol use disorder (AUD) represents a major gap in public health information.
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            The prevalence of hepatitis C virus infection in the United States, 1999 through 2002.

            Defining the primary characteristics of persons infected with hepatitis C virus (HCV) enables physicians to more easily identify persons who are most likely to benefit from testing for the disease. To describe the HCV-infected population in the United States. Nationally representative household survey. U.S. civilian, noninstitutionalized population. 15,079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002. All participants provided medical histories, and those who were 20 to 59 years of age provided histories of drug use and sexual practices. Participants were tested for antibodies to HCV (anti-HCV) and HCV RNA, and their serum alanine aminotransferase (ALT) levels were measured. The prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), equating to an estimated 4.1 million (CI, 3.4 million to 4.9 million) anti-HCV-positive persons nationwide; 1.3% or 3.2 million (CI, 2.7 million to 3.9 million) persons had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was observed among persons 40 to 49 years of age. A total of 48.4% of anti-HCV-positive persons between 20 and 59 years of age reported a history of injection drug use, the strongest risk factor for HCV infection. Of all persons reporting such a history, 83.3% had not used injection drugs for at least 1 year before the survey. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 58.7% of HCV RNA-positive persons. Three characteristics (abnormal serum ALT level, any history of injection drug use, and history of blood transfusion before 1992) identified 85.1% of HCV RNA-positive participants between 20 and 59 years of age. Incarcerated and homeless persons were not included in the survey. Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.
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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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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                28 June 2019
                June 2019
                28 June 2019
                : 2
                : 6
                : e196412
                Affiliations
                [1 ]Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis
                [2 ]Regenstrief Institute, Inc, Indianapolis, Indiana
                Author notes
                Article Information
                Accepted for Publication: May 12, 2019.
                Published: June 28, 2019. doi:10.1001/jamanetworkopen.2019.6412
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Orman ES et al. JAMA Network Open.
                Corresponding Author: Eric S. Orman, MD, MSCR, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Cir, Ste 225, Indianapolis, IN 46202 ( esorman@ 123456iu.edu ).
                Author Contributions: Dr Orman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Orman, Ghabril, Nephew, Chalasani.
                Acquisition, analysis, or interpretation of data: Orman, Roberts, Ghabril, Desair, Patidar, Chalasani.
                Drafting of the manuscript: Orman, Chalasani.
                Critical revision of the manuscript for important intellectual content: Orman, Roberts, Ghabril, Nephew, Desai, Patidar.
                Statistical analysis: Orman, Ghabril, Patidar.
                Obtained funding: Orman.
                Administrative, technical, or material support: Nephew.
                Supervision: Ghabril, Chalasani.
                Conflict of Interest Disclosures: Dr Chalasani reported ongoing consulting activities (within the preceding 12 months) with NuSirt, Abbvie, Eli Lilly and Co, Afimmune (DS Biopharma), Allergan (Tobira), Madrigal, Shire, Axovant, Coherus, Pronova (BASF), and Genentech; and receiving research grant support from Intercept, Eli Lilly and Co, Exact Sciences, Galectin Therapeutics, and Cumberland outside the submitted work. No other disclosures were reported.
                Funding/Support: This study was supported in part by the Indiana Clinical and Translational Sciences Institute, which is funded in part by Clinical and Translational Sciences Award KL2TR001106 from the National Center for Advancing Translational Sciences, National Institutes of Health. This study was also supported in part by grant K23DK109202 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
                Article
                zoi190254
                10.1001/jamanetworkopen.2019.6412
                6604080
                31251379
                aac9ccbc-f01c-4e4b-a5b4-fcbbd4b96b91
                Copyright 2019 Orman ES et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 2 March 2019
                : 12 May 2019
                Funding
                Funded by: Indiana Clinical and Translational Sciences Institute
                Funded by: National Center for Advancing Translational Sciences
                Funded by: National Institutes of Health
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases
                Funded by: National Institutes of Health
                Categories
                Research
                Original Investigation
                Online Only
                Gastroenterology and Hepatology

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