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. 2021 Jul;70(7):1375-1382.
doi: 10.1136/gutjnl-2020-322786. Epub 2020 Oct 9.

Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort

Tracey G Simon  1   2   3 , Bjorn Roelstraete  4 , Hamed Khalili  1   2   3 , Hannes Hagström  5 , Jonas F Ludvigsson  6   7   8   9   10
Affiliations

Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort

Tracey G Simon et al. Gut. 2021 Jul.

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.

Keywords: epidemiology; fatty liver; fibrosis; hepatocellular carcinoma; liver cirrhosis.

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Conflict of interest statement

Competing interests: JFL coordinates a study on behalf of the Swedish Inflammatory Bowel Disease quality register (SWIBREG), that has received funding from Janssen Corporation. HH reports research grants to his institution from AstraZeneca, Intercept and Gilead, and board advisory for Bristol Myers Squibb and Gilead. TS has served as a consultant to Aetion for work unrelated to this manuscript.

Figures

Figure 1.
Figure 1.
Cumulative Incidence of All-Cause Mortality According to the Presence and Histologic Severity* of NAFLD Abbreviations: NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; ref., reference group *NAFLD histologic severity was defined in 4 categories, as simple steatosis, NASH without fibrosis, non-cirrhotic fibrosis and cirrhosis (for details, see the eMethods section)
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References

    1. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64(1):73–84. doi: 10.1002/hep.28431 [published Online First: 2015/12/29] - DOI - PubMed
    1. Wong RJ, Liu B, Bhuket T. Significant burden of nonalcoholic fatty liver disease with advanced fibrosis in the US: a cross-sectional analysis of 2011–2014 National Health and Nutrition Examination Survey. Alimentary pharmacology & therapeutics 2017;46(10):974–80. doi: 10.1111/apt.14327 [published Online First: 2017/09/16] - DOI - PubMed
    1. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary pharmacology & therapeutics 2011;34(3):274–85. doi: 10.1111/j.1365-2036.2011.04724.x [published Online First: 2011/06/01] - DOI - PubMed
    1. Taylor RS, Taylor RJ, Bayliss S, et al. Association Between Fibrosis Stage and Outcomes of Patients with Non-Alcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. Gastroenterology 2020. doi: 10.1053/j.gastro.2020.01.043 [published Online First: 2020/02/07] - DOI - PubMed
    1. Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 2017;65(5):1557–65. doi: 10.1002/hep.29085 [published Online First: 2017/01/29] - DOI - PMC - PubMed

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