| 11. |
- Simon, Tracey G., et al.
(författare)
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Mortality in biopsy-confirmed nonalcoholic fatty liver disease : results from a nationwide cohort
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1375-1382
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Tidskriftsartikel (refereegranskat)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)(p trend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (p trend <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.
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| 12. |
- Simon, Tracey G., et al.
(författare)
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Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:5, s. 1034-1041
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Longitudinal data are scarce regarding the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD).Methods: This nationwide, matched cohort study included all Swedish children and young adults (<= 25 years) with biopsy confirmed NAFLD (1966-2017; n = 718). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, and further categorized as simple steatosis or steatohepatitis (NASH). Patients with NAFLD were matched to <= 5 general population controls by age, sex, calendar year and county (n = 3,457). To account for shared genetic and early-life factors, we also matched patients with NAFLD to full sibling comparators. Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% CIs.Results: Over a median of 15.8 years, 59 patients with NAFLD died (5.5/1,000 person-years [PY]) compared to 36 population controls (0.7/1,000 PY; difference = 4.8/1,000 PY; multivariable aHR 5.88; 95% CI 3.77-9.17), corresponding to 1 additional death per 15 patients with NAFLD, followed for 20 years. The 20-year absolute risk of overall mortality was 7.7% among patients with NAFLD, and 1.1% among controls (difference = 6.6%; 95% CI 4.0-9.2). Findings persisted after excluding those who died within the first 6 months (aHR 4.65; 95% CI 2.92-7.42), and after using full-sibling comparators (aHR 11.72; 95% CI 3.18-43.23). Simple steatosis was associated with a 5.26-fold higher adjusted rate of mortality compared to controls (95% CI 3.05-9.07), and this was amplified with NASH (aHR 11.51, 95% CI 4.77-27.79). Most of the excess mortality was from cancer (1.67 vs. 0.07/ 1,000PY; aHR 15.60; 95% CI 4.97-48.93), liver disease (0.93 vs. 0.04/1,000PY; aHR 16.46; 95% CI 2.75-98.43) and cardiometabolic disease (1.12 vs. 0.14/1,000PY; aHR 4.32, 95% CI 1.73-10.79).Conclusions: Swedish children and young adults with biopsy confirmed NAFLD have significantly higher rates of overall, cancer-, liver-and cardiometabolic-specific mortality compared to matched general population controls.Lay summary: Currently, the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) is unknown. This nationwide cohort study compared the risk of all-cause and cause-specific mortality in pediatric and young adult patients in Sweden with biopsy-confirmed NAFLD to matched general population controls. We found that compared to controls, children and young adults with biopsy-confirmed NAFLD and NASH have significantly higher rates of overall, cancer-, liver-and cardiometabolic-specific mortality.
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