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43rd Annual Meeting of the European Association For The Study Of The Liver
Milan, Italy
April 23-27, 2008
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  Reported by Jules Levin
43rd Annual EASL Conference, April 23-27, 2008, Milan, Italy
J.P. Ong1,2,3, A. Pitts4, Z.M. Younossi1,2
1 Center For Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA;
2 Outcomes Research Program, Inova Health System, Falls Church, VA, Uas;
3 Department Of Medicine, University Of The Philippines, Manila, The Philippines;
4 RTI International, Research Triangle Park, NC, USA
Limitations of study

--no histological or radiologic confirmation of NAFLD.
--presumed dignosis of NAFLD was based on clinical and laboratory data.
--NHANES may underestimate the true prevalence of NAFLD
Strength of Study
--large population cohort with extensive clinical-laboraotory data as well as NDI-Plus mortality data and relatively long followup.
--NAFLD is associated with higher mortality as well as higher liver reated mortality (the hazard ratio for liver-related mortality was high, data below).
--cardiovascular disease and malignancy remain the top two causes of death among persons with NAFLD.
--liver disease is an important cause of death among persons with NAFLD, being 3rd leading cause of death.
--this population-based study confirms data obtained from tertiary care medical centers and community cohort.
Of particular note adjusted hazard ratio for liver-related mortality:
Adjusted for age, gender, race, education, income, BMI, HTN, DM: hazard ratio
9.32 (9.21, 9.43) (p<0.0001); adjusted for age, gender, race, education, income:
9.22 (9.11, 9.33) (p<0.0001)
Program Abstract

NAFLD is one of the most common causes of chronic liver disease.
AIM: To determine the overall and liver-related mortality of NAFLD in the general US population and to determine the causes of mortality.
METHODS: In this study, we utilized Third National Health and Nutrition Examination Survey (NHANES III) and Linked Mortality Files. NAFLD was defined as having elevated serum aminotransferases in the absence of significant alcohol use, elevated transferrin saturation or hepatitis B or C. Adjusted hazard ratios for overall mortality and liver-related mortality were calculated for NAFLD using persons without liver disease as the reference. Cox proportional hazards model was used. SAS and SUDAAN were used for the analysis and to account for the weighted sampling in NHANES III. The various causes of death were determined for each cohorts.
Final database included 817 NAFLD and 10,468 persons without any liver disease. NAFLD patients were younger, more likely to be male, less likely to be white, have lower income, less educated, more likely to be obese, have hypertension, diabetes mellitus, or metabolic syndrome. After a median follow up of 8.74 years, 1,533 persons have died.
Among those who died, 80 had NAFLD and 1,453 were controls without liver disease.
In NAFLD cohort, older age, male gender, non-Hispanic white race, lower educational level, lower income, higher BMI, presence of hypertension, diabetes mellitus, or metabolic syndrome were significantly (p<0.05) associated with overall mortality.
Overall mortality remained significantly higher in NAFLD cohort after adjusting for important confounders [Hazard Ratio 1.113 (95% CI 1.110-1.116)]. Furthermore, liver-related mortality remained significantly (P<0.05) higher in NAFLD cohort, even after adjusting for confounders [Hazard Ratio 9.22 (95% CI 9.11-9.33)].
Adjusted hazard ratio for overall mortality for persons with NAFLD: --adjusted for age, gender, race, income, BMI, HTN, and DM: HR 1.038 (1.036, 1.041 (p<0.0001); adjusted for age, gender, race, education, income, and MS: 1.117 (1.114, 1.120) (p<0.0001).
Cardiovascular diseases and malignancy were the two leading causes of death in the NAFLD cohort. Liver disease was the third leading cause of death in NAFLD. On the other hand, liver disease was the 11th cause of death in persons without liver disease.
CONCLUSIONS: NAFLD patients are at higher risk for mortality and liver-related mortality in the US general population. Although cardiovascular diseases remain the leading cause of death in the NAFLD cohort, liver-related mortality was the third leading cause of death.