Data were obtained from the CDC WONDER platform (see supplemental material for more details).17 (link) Our primary aim was to describe temporal trends in death rates attributable to cirrhosis (ICD-10 (international classification of diseases, 10th revision) codes K70.3, K74.5, and K74.6) and hepatocellular carcinoma (C22.0) as the primary or underlying cause of death for adults in the USA. We adjusted rates for age—that is, age specific mortality was weighted according to the age distribution in a standard year (2000).18 (link) We also sought to describe how these trends differed based on demographic subgroups; age, sex, race (Asian or Pacific Islander, Native American (designated as “American Indian” in the census database) or Alaska Native, black or African American, and white American), Hispanic ethnicity, and geographic area of residence. We also aimed to describe trends in causes of death related to specific complications associated with cirrhosis. Specifically, we examined death due to gastrointestinal hemorrhage (ICD-10 K25-K28, K92.0-K92.2, I85.0), peritonitis (K65), sepsis (A41), hepatorenal syndrome (K76.7), and traumas (V01-Y89). Given the association between non-alcoholic fatty liver disease and complications of the metabolic syndrome such as cerebrovascular disease and ischemic heart disease (I20-I25, I60-I69),19 (link) we evaluated trends in mortality due to cirrhosis comorbid with these conditions. We also compared trends in deaths due to alcohol use disorder (F10).
To test for unmeasured secular trends, we compared all findings with death rates due to causes other than cirrhosis. Specifically, we examined the trends in deaths due to infections (ICD-10 A00-B99), neoplasia (C00-C48, not including hepatocellular carcinoma, C22), cardiovascular disease (I00-I99), and respiratory disease (J00-J98). Finally, we assessed overall trends in several US states that were observed to have the greatest increase or highest death rates due to cirrhosis and hepatocellular carcinoma (eg, Arizona, New Mexico, and Wyoming).
We performed several sensitivity analyses. First we evaluated trends when the cause of death was labeled as any liver disease with or without cirrhosis (ICD-10 K70-K76). Next we evaluated trends when the death certificate included any mention of cirrhosis as a primary or contributory cause; a death certificate can have a primary or underlying cause and up to 20 contributing causes. Finally, we repeated the trend analysis that included age adjusted death rate estimates by standardizing rates to different years (2000, 2009, and 2010) and sex (men or women).
To test for unmeasured secular trends, we compared all findings with death rates due to causes other than cirrhosis. Specifically, we examined the trends in deaths due to infections (ICD-10 A00-B99), neoplasia (C00-C48, not including hepatocellular carcinoma, C22), cardiovascular disease (I00-I99), and respiratory disease (J00-J98). Finally, we assessed overall trends in several US states that were observed to have the greatest increase or highest death rates due to cirrhosis and hepatocellular carcinoma (eg, Arizona, New Mexico, and Wyoming).
We performed several sensitivity analyses. First we evaluated trends when the cause of death was labeled as any liver disease with or without cirrhosis (ICD-10 K70-K76). Next we evaluated trends when the death certificate included any mention of cirrhosis as a primary or contributory cause; a death certificate can have a primary or underlying cause and up to 20 contributing causes. Finally, we repeated the trend analysis that included age adjusted death rate estimates by standardizing rates to different years (2000, 2009, and 2010) and sex (men or women).
