1. Slideset on: Asrani SK, Larson JJ, Yawn B, et al. Underestimation of liver-related mortality in the United States. Gastroenterology. 2013;145:375-82. Liver Disease–Related Mortality in United States Underestimated Over Past 30+ Years This program is supported by educational grants from

2. inPractice.com United States Liver Disease-Related Mortality Underestimated Background  Chronic liver disease and cirrhosis ranked as 12th leading cause of mortality in US according to NCHS [1] –Estimated 30,000 deaths each yr –4th leading cause of death in persons aged 45-54 yrs  Descriptors may not adequately capture all deaths due to liver diseases, such as hepatic encephalopathy, hepatorenal syndrome, liver cancer, and viral hepatitis  Important to capture accurate data on liver disease–related mortality to correctly inform public health policy and resource allocation  Current study evaluated liver disease–related mortality in US using population-based data and broader set of descriptors than that employed by NCHS [2] 1. Heron M. Natl Vital Stat Rep. 2012;60:1-94. 2. Asrani SK, et al. Gastroenterology. 2013;145:375-382.

3. inPractice.com United States Liver Disease-Related Mortality Underestimated Summary of Study Design  Mortality data obtained from 2 population-based sources –Rochester Epidemiology Project featuring data from 1999- 2008 on individuals in Olmsted County, Minnesota –National Death Registry featuring data from 1979-2008 on individuals in all 50 states and Washington, DC  Identified liver-specific deaths for individuals aged 15 yrs or older –Rochester Epidemiology Project used multiple resources to determine accuracy of cause of death on death certificate vs data in medical records Asrani SK, et al. Gastroenterology. 2013;145:375-382.

4. inPractice.com United States Liver Disease-Related Mortality Underestimated Description of Current Analysis  Information extracted from death records –Immediate and underlying causes of death –Contributing causes of death (other significant conditions contributing to death but not resulting in underlying cause)  Causes of death classified according to International Classification of Diseases –9th revision used for deaths from 1979-1998 –10th revision used for deaths from 1999-2008 Asrani SK, et al. Gastroenterology. 2013;145:375-382.

5. inPractice.com United States Liver Disease-Related Mortality Underestimated Description of Current Analysis  Narrow NCHS definition (including only chronic liver disease and cirrhosis as liver disease–related causes of death) expanded to include: –Viral hepatitis –Hepatobiliary cancers –Other specific liver diagnoses (eg, hepatorenal syndrome)  Age- and sex-adjusted death rates calculated for both population-based data sets –Estimates adjusted to US 2000 census population to derive standardized rates –Separate rates determined for deaths using NCHS definition and updated definition –Estimated rates further broken down by age (by deciles), sex, and race Asrani SK, et al. Gastroenterology. 2013;145:375-382.

6. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  NCHS definition identified 71 liver disease–related deaths in Rochester Epidemiology Project database  Updated definitions identified 261 liver disease–related deaths in Rochester Epidemiology Project database –Age- and sex-adjusted death rate: 27/100,000 individuals –Cause of death –40.6% (106/261) captured by expanded liver disease– related definitions (inclusive of 71 NCHS-defined deaths) –32.6% (85/261) due to viral hepatitis –26.8% (70/261) due to hepatobiliary malignancies Asrani SK, et al. Gastroenterology. 2013;145:375-382.

7. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  Characteristics of decedents using updated definitions generally consistent with characteristics of decedents identified using NCHS definition –Mean age at death: 59 ± 15 yrs –Deaths in individuals aged 45-64 yrs: 52.5% –Deaths in men: 80.5% –Expanded definitions captured more liver disease–related deaths based on race and included proportionally fewer inpatient deaths –Blacks (16.3% vs 7.0% with NCHS definition) –Other races (5.7% vs 4.2% with NCHS definition) –Hispanic (5.8% vs 4.2% with NCHS definition) –Fewer inpatient deaths (25% vs 52% with NCHS definition) Asrani SK, et al. Gastroenterology. 2013;145:375-382.

8. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings Characteristic Deaths According to NCHS Definition (n = 71) Liver Disease– Related Deaths, Not Including NCHS-Defined Deaths (n = 190) Deaths According to Updated Definitions, Including NCHS- Defined Deaths (n = 261) Median age, yrs (SD)57.7 (12.6)59.3 (15.6)59.0 (15.0) Women, %22.518.419.5 Race, %  White88.777.981.0  Black7.016.314.0  Hispanic4.25.85.0  Other4.25.75.0 Death in inpatient setting, % 52.124.932.0 Asrani SK, et al. Gastroenterology. 2013;145:375-382.

9. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  84 deaths identified in Rochester Epidemiology Project database occurred in inpatient setting, allowing comparison of death certificate diagnosis and circumstances surrounding death –Death certificate correctly classified cause of death in 97.6% of cases  Liver disease–related cause of death correctly classified as immediate cause in majority of patients dying from viral hepatitis or hepatobiliary cancer –Viral hepatitis: 96.9% of 98 cases –Hepatobiliary cancer: 94.3% of 70 cases Asrani SK, et al. Gastroenterology. 2013;145:375-382.

10. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  NCHS definition identified 29,951 liver disease–related deaths in National Death Registry database  Updated definitions identified 66,007 liver disease–related deaths in National Death Registry database –Age- and sex-adjusted death rate: 25.7/100,000 individuals Asrani SK, et al. Gastroenterology. 2013;145:375-382.

11. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings Cause of DeathDeaths, nRate per 100,000 Individuals NCHS definition29,95111.7  Fibrosis and cirrhosis of the liver14,9955.8  Alcoholic liver disease14,8645.2  Chronic hepatitis920.2 Expanded definitions  Other liver diagnosis10,2564.0 Liver disease, unspecified36881.4 Hepatic failure, unspecified36131.4 Other1695NA Fatty liver, not elsewhere classified7930.3 Hepatorenal syndrome4670.2 Asrani SK, et al. Gastroenterology. 2013;145:375-382.

12. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings Cause of DeathDeaths, nRate per 100,000 Individuals Expanded definitions  Viral hepatitis76252.9 Chronic hepatitis C68342.6 Acute hepatitis B5090.2 Chronic hepatitis B1620.1 Other120NA  Hepatobiliary cancer18,1757.1 Liver cell carcinoma75612.9 Liver, unspecified65512.6 Intrahepatic bile duct carcinoma40371.6 Other26NA Updated estimate*66,00725.7 *Updated estimate = NCHS definition + other liver diagnosis + viral hepatitis + hepatobiliary cancer. Asrani SK, et al. Gastroenterology. 2013;145:375-382.

13. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  Liver disease caused large number of premature deaths regardless of definition –Largest number of deaths occurred between ages 45-64 yrs –Highest mortality in oldest age group –Consistently higher mortality men vs women across all age groups Definition (per 100,000 Persons) Age, Yrs 25-3435-4445-5455-6465-7475-8485+ NCHS1.06.018.525.326.828.119.9  Men1.47.926.437.636.535.327.2  Women0.74.110.813.918.623.216.4 Updated*1.99.435.455.761.579.368.9  Men2.212.151.483.083.3103.090.8  Women1.56.819.830.242.862.958.2 *Updated estimate = NCHS definition + other liver diagnosis + viral hepatitis + hepatobiliary cancer. Asrani SK, et al. Gastroenterology. 2013;145:375-382.

14. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  All racial groups experienced increased liver disease–related mortality  Liver disease–related mortality underestimation by NCHS definition varied according to race –NCHS definition captured 47% of liver disease–related deaths in whites vs 20% and 34% Asians and blacks, respectively –Among Asians and blacks, excess deaths driven by hepatobiliary malignancy (56%) and viral hepatitis (14%) –Among American Indians/Alaska natives, excess deaths driven by expanded liver diagnosis (16%) –Excess deaths among Hispanics driven by expanded liver diagnosis (14%) and viral hepatitis (14%) Asrani SK, et al. Gastroenterology. 2013;145:375-382.

15. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings Race Overall Adjusted Mortality per 100,000 Individuals, by Diagnosis NCHS Definition Expanded Liver Diagnosis Viral Hepatitis Hepatobiliary Malignancies Updated Estimate* White12.24.02.86.525.5 Black8.74.43.89.326.2 Asian4.32.23.012.622.1 American Indian/Alaska native 30.08.83.88.350.9 Hispanic17.85.44.910.738.8 *Updated estimate = NCHS definition + other liver diagnosis + viral hepatitis + hepatobiliary cancer. Asrani SK, et al. Gastroenterology. 2013;145:375-382.

16. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  By NCHS definition, liver disease–related deaths decreased by 38% from 1979-1988 to 1999-2008  Updated definitions demonstrated little change in liver disease–related deaths over time, largely due to increasing deaths from viral hepatitis and hepatobiliary cancer –Largest increases in age-specific mortality during recent era (1999-2008) between 45-64 yrs and 55-64 yrs of age –Largest change in age-specific mortality during recent era among individuals 55-64 yrs of age, driven by increase in hepatobiliary malignancies –1999: 8.8/100,000 –2008: 14.1/100,000 Asrani SK, et al. Gastroenterology. 2013;145:375-382.

17. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings Era Overall Adjusted Mortality per 100,000 Individuals, by Diagnosis NCHS Definition Expanded Liver Diagnosis Viral Hepatitis Hepatobiliary Malignancies Updated Estimate* Era 1 (1979-1998) 16.53.10.53.823.9 Era 2 (1989-1998) 13.03.11.55.222.8 Era 3 (1999-2008) 11.73.82.56.424.4 *Updated estimate = NCHS definition + other liver diagnosis + viral hepatitis + hepatobiliary cancer. Asrani SK, et al. Gastroenterology. 2013;145:375-382.

18. inPractice.com United States Liver Disease-Related Mortality Underestimated Main Findings  Longitudinal changes identified in age-specific death rates for liver disease– related mortality –Rates decreased over time in individuals younger than 45 yrs of age –Rates increased over time in individuals older than 75 yrs of age Age, Yrs Unadjusted Mortality per 100,000 Individuals 19792008Change, % 25-344.41.9-56.8 35-4416.29.4-42.0 45-5437.035.4-4.3 55-6452.955.7+5.3 65-7461.5 0 75-8454.579.3+45.5 ≥ 8553.268.9+29.5 Asrani SK, et al. Gastroenterology. 2013;145:375-382.

19. inPractice.com United States Liver Disease-Related Mortality Underestimated Other Outcomes  Liver disease–related death rates generally consistent between Rochester Epidemiology Project and National Death Registry databases –Overall updated death rates similar –Death rate due to viral hepatitis somewhat higher in Rochester Epidemiology Project database, but offset by somewhat lower death rate due to NCHS-defined deaths and expanded liver diagnosis deaths Asrani SK, et al. Gastroenterology. 2013;145:375-382.

20. inPractice.com United States Liver Disease-Related Mortality Underestimated Other Outcomes Factor Adjusted Mortality per 100,000 Individuals Rochester Epidemiology Project National Death Registry Updated estimate of cause of death27.024.5  NCHS-defined deaths7.311.7  Expanded liver diagnosis11.015.5  Viral hepatitis8.62.5  Hepatobiliary cancer7.46.4 Deaths by sex  Male46.434.0  Female9.216.2 Deaths by age  45-54 yrs48.633.8  55-64 yrs46.046.7 Asrani SK, et al. Gastroenterology. 2013;145:375-382.

21. inPractice.com United States Liver Disease-Related Mortality Underestimated Summary of Key Conclusions  Expanded definitions of liver disease–related causes of death identify substantial underestimation of liver disease– related mortality incidence in United States since at least 1979 –Rochester Epidemiology Project database age- and sex- adjusted mortality increased from 7.3 to 27.0 deaths per 100,000 individuals –National Death Registry database age- and sex-adjusted mortality increased from 11.7 to 25.7 deaths per 100,000 individuals  Liver disease–related mortality systematically underestimated in blacks, Asians, and Hispanics Asrani SK, et al. Gastroenterology. 2013;145:375-382.

22. inPractice.com United States Liver Disease-Related Mortality Underestimated Summary of Key Conclusions  Narrow NCHS definition led to perceived decreases in liver disease–related deaths from 1979-2008 –Expanded definitions indicate mortality essentially unchanged during same period  Findings support inclusion of deaths due to viral hepatitis and hepatobiliary cancers in definition of liver disease– related deaths to accurately represent burden of chronic liver disease Asrani SK, et al. Gastroenterology. 2013;145:375-382.

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