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.

Advances in imaging techniques such as vibration-controlled transient elastography and magnetic resonance elastography have reduced the need for liver biopsy as a means of diagnosing liver disease.

Background and Aims: Electronic health record (EHR)‐based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. Approach and Results: Researchers with an interest in EHR‐based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR‐based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. Conclusions: This expert panel consensus statement can help harmonize and improve generalizability of EHR‐based NAFLD research.