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Abstract Details
Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort
Gut. 2020 Oct 9;gutjnl-2020-322786. doi: 10.1136/gutjnl-2020-322786. Online ahead of print.
Tracey G Simon123, Bjorn Roelstraete4, Hamed Khalili123, Hannes Hagström5, Jonas F Ludvigsson678910
Author information
1Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA.
3Harvard Medical School, Boston, MA, USA.
4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Stockholm County, Sweden.
5Center for Digestive Diseases, Division of Hepatology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
6Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Stockholm County, Sweden jonasludvigsson@yahoo.com.
7Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Stockholm, Sweden.
8Department of Pediatrics, Orebro University Hospital, Orebro, Sweden.
9Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
10Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Abstract
Objective: Population-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD).
Design: This nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to ≤5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs.
Results: Over a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(ptrend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (ptrend <0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30).
Conclusion: All NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.