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Journal of hepatology : the journal of the European Association for the Study of the Liver v.67 no.6, 2017년, pp.1265 - 1273   SCI SCIE
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Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD

Hagström, Hannes (Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden ) ; Nasr, Patrik (Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden ) ; Ekstedt, Mattias (Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden ) ; Hammar, Ulf (Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Sweden ) ; Stål, Per (Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden ) ; Hultcrantz, Rolf (Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden ) ; Kechagias, Stergios (Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden ) ;
  • 초록  

    Background & Aims Non-alcoholic fatty liver disease (NAFLD) is very common in the general population, but identifying patients with increased risk of mortality and liver-specific morbidity remains a challenge. Non-alcoholic steatohepatitis (NASH) is thought to enhance this risk; therefore, resolution of NASH is a major endpoint in current pharmacologic studies. Herein, we aim to investigate the long-term prognosis of a large cohort of NAFLD patients, and to study the specific effect of NASH and fibrosis stage on prognosis. Methods We conducted a retrospective cohort study of 646 biopsy-proven NAFLD patients. Each case was matched for age, sex and municipality to ten controls. Outcomes on mortality and severe liver disease, defined as cirrhosis, liver decompensation/failure or hepatocellular carcinoma, were evaluated using population-based registers. Cox regression models adjusted for age, sex and type 2 diabetes were used to examine the long-term risk according to fibrosis stage. Likelihood ratio tests were used to assess whether adding NASH to these models increased the predictive capacity. Laplace regression was used to estimate the time to severe liver disease according to stage of fibrosis. Results During a follow-up of mean 20years (range 0–40) equivalent to 139,163 person-years, 12% of NAFLD patients and 2.2% of controls developed severe liver disease ( p 0.05 for all stages of fibrosis). Similar results were seen for overall mortality. The lower end of the 95% confidence interval for the 10 th percentile of time to development of severe liver disease was 22–26years in F0-1, 9.3years in F2, 2.3years in F3, and 0.9years to liver decompensation in F4. Conclusions In this, the largest ever study of biopsy-proven NAFLD, the presence of NASH did not increase the risk of liver-specific morbidity or overall mortality. Knowledge of time to development of severe liver disease according to fibrosis stage can be used in individual patient counselling and for public health decisions. Lay summary Non-alcoholic fatty liver disease (NAFLD) is very common in the general population, but reaching an accurate prognosis remains challenging. We investigate the long-term prognosis of a large cohort of NAFLD patients. In this, the largest ever study of biopsy-proven NAFLD, the presence of NASH did not increase the risk of liver-specific morbidity or overall mortality. Knowledge of time to development of severe liver disease according to fibrosis stage can be used in individual patient counselling and for public health decisions. Highlights Identifying NAFLD patients at a high risk of adverse outcomes is a challenge. Herein, we present data from the largest cohort study of NAFLD patients to date. Presence of NASH did not increase the risk of adverse outcomes. Time to severe liver disease according to stage of fibrosis is reported. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Steatosis .   Cirrhosis .   Epidemiology.  

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