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. 2017 Jul;66(1):84-95.
doi: 10.1002/hep.29113. Epub 2017 May 16.

Liver fibrosis scores predict liver disease mortality in the United States population

Aynur Unalp-Arida  1 , Constance E Ruhl  2
Affiliations

Liver fibrosis scores predict liver disease mortality in the United States population

Aynur Unalp-Arida et al. Hepatology. 2017 Jul.

Abstract

Fatty liver disease is common in the United States and worldwide due to changing lifestyles and can progress to fibrosis and cirrhosis contributing to premature death. We examined whether liver fibrosis scores were associated with increased overall and disease-specific mortality in a United States population-based prospective survey with up to 23 years of linked-mortality data. Data were analyzed from 14,841 viral hepatitis-negative adult participants in the third National Health and Nutrition Examination Survey, 1988-1994. Liver fibrosis was predicted using the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and Forns score. Participants were passively followed for mortality, identified by death certificate underlying or contributing causes, by linkage to National Death Index records through 2011. Hazard ratios (HR) for mortality were calculated using Cox proportional hazards regression to adjust for mortality risk factors. During follow-up, cumulative mortality was 28.0% from all causes and 0.82% with liver disease, including primary liver cancer. Elevated liver disease mortality was found with an intermediate to high APRI (HR, 9.44; 95% confidence interval [CI], 5.02-17.73), intermediate (HR, 3.15; 95% CI, 1.33-7.44) or high (HR, 25.14; 95% CI, 8.38-75.40) FIB-4 score, high NFS (HR, 6.52; 95% CI, 2.30-18.50), and intermediate (HR, 3.58; 95% CI, 1.78-7.18) or high (HR, 63.13; 95% CI, 22.16-179.78) Forns score. Overall mortality was also greater with higher fibrosis scores.

Conclusion: In the United States population, higher liver fibrosis scores were associated with increased liver disease and overall mortality. Liver health management with common clinical measures of fibrosis risk stratification merits further investigation. (Hepatology 2017;66:84-95).

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Figures

Figure 1.
Figure 1.
Derivation of NHANES III sample for analysis of liver fibrosis scores and mortality. NHANES, National Health and Nutrition Examination Survey; HBV sAg+, hepatitis B virus surface antigen positive; HCV RNA+, hepatitis C virus ribonucleic acid positive; AST, aspartate aminotransferase; ALT, alanine aminotransferase; BMI, body mass index; GGT, gamma glutamyltransferase; APRI, AST to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 2.
Figure 2.
Multivariate-adjusted mortality hazard ratios and 95% confidence intervals by APRI, FIB-4, NFS, or Forns category in NHANES III, United States, 1988–2011. (A) All-cause mortality (B) Cardiovascular disease mortality (C) Mortality from neoplasms (D) Diabetes mortality (E) Liver disease mortality NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 2.
Figure 2.
Multivariate-adjusted mortality hazard ratios and 95% confidence intervals by APRI, FIB-4, NFS, or Forns category in NHANES III, United States, 1988–2011. (A) All-cause mortality (B) Cardiovascular disease mortality (C) Mortality from neoplasms (D) Diabetes mortality (E) Liver disease mortality NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 2.
Figure 2.
Multivariate-adjusted mortality hazard ratios and 95% confidence intervals by APRI, FIB-4, NFS, or Forns category in NHANES III, United States, 1988–2011. (A) All-cause mortality (B) Cardiovascular disease mortality (C) Mortality from neoplasms (D) Diabetes mortality (E) Liver disease mortality NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 2.
Figure 2.
Multivariate-adjusted mortality hazard ratios and 95% confidence intervals by APRI, FIB-4, NFS, or Forns category in NHANES III, United States, 1988–2011. (A) All-cause mortality (B) Cardiovascular disease mortality (C) Mortality from neoplasms (D) Diabetes mortality (E) Liver disease mortality NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 2.
Figure 2.
Multivariate-adjusted mortality hazard ratios and 95% confidence intervals by APRI, FIB-4, NFS, or Forns category in NHANES III, United States, 1988–2011. (A) All-cause mortality (B) Cardiovascular disease mortality (C) Mortality from neoplasms (D) Diabetes mortality (E) Liver disease mortality NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 3.
Figure 3.
Multivariate-adjusted cumulative liver disease mortality by liver fibrosis score category in NHANES III, United States, 1988–2011. (A) APRI (B) FIB-4 (C) NFS (D) Forns NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 3.
Figure 3.
Multivariate-adjusted cumulative liver disease mortality by liver fibrosis score category in NHANES III, United States, 1988–2011. (A) APRI (B) FIB-4 (C) NFS (D) Forns NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 3.
Figure 3.
Multivariate-adjusted cumulative liver disease mortality by liver fibrosis score category in NHANES III, United States, 1988–2011. (A) APRI (B) FIB-4 (C) NFS (D) Forns NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
Figure 3.
Figure 3.
Multivariate-adjusted cumulative liver disease mortality by liver fibrosis score category in NHANES III, United States, 1988–2011. (A) APRI (B) FIB-4 (C) NFS (D) Forns NHANES, National Health and Nutrition Examination Survey; APRI, aspartate aminotransferase to platelet ratio index; FIB-4, fibrosis-4; NFS, non-alcoholic fatty liver disease fibrosis score.
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