Progression of liver fibrosis is associated with non-liver-related mortality in patients with nonalcoholic fatty liver disease.

In patients with nonalcoholic fatty liver disease (NAFLD), prognosis and outcome, especially non-liver-related mortality, remain incompletely elucidated. We clarified the mortality from all causes in patients with NAFLD. A total of 4,073 patients with NAFLD diagnosed by ultrasonography were enrolled. We investigated the causes of death and analyzed the mortality from non-liver-related diseases according to the degrees of steatosis and fibrosis using the competing risk method. We used the NAFLD fibrosis score (NFS) to assess fibrosis severity and the ultrasonography fatty liver score to evaluate steatosis severity. The numbers of patients with NFS indicating low, intermediate, and high probabilities of advanced fibrosis were 2,451 (60.2%), 1,462 (35.9%), and 160 (3.9%), respectively. Of the 4,073 patients, 179 died during follow-up, but only nine deaths were due to liver-related diseases. Of the remaining 170 patients who died due to non-liver-related diseases, 83 (48.8%), 42 (24.7%), and 45 (26.5%) patients died due to malignancies, cerebrovascular and cardiovascular diseases, and benign diseases (excluding cerebrovascular and cardiovascular diseases), respectively. Multivariate analysis showed that the intermediate and high NFS groups were independently associated with each disease category: hazard ratio (HR) 2.163 (95% confidence interval [CI], 1.354-3.457) and HR 4.814 (95% CI, 2.323-9.977) for malignancies; HR 2.265 (95% CI, 1.141-4.497) and HR 8.482 (95% CI, 3.558-20.220) for cerebrovascular and cardiovascular diseases; and HR 3.216 (95% CI, 1.641-6.303) and HR 5.558 (95% CI, 1.923-16.070) for benign diseases, respectively. Conversely, the status of steatosis was not associated with risk of mortality in multivariate analysis. Conclusion: Progression of liver fibrosis severity was associated with mortality from various non-liver-related causes in patients with NAFLD. (Hepatology Communications 2017;1:928-945).