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Project properties

Title	Epidemiology and risk factors of NASH
Keywords	epidemiology risk factors NASH
Researchers	dr. J. Blokzijl E.H. Wouters-van den Berg
Nature of the research	Mapping the epidemiology and risk factors of NAFLD, NASH and NASH-fibrosis
Fields of study	gastroenterology

Background / introduction

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of significant alcohol intake and by the presence of triglyceride accumulation in more than 5% of hepatocytes [1]. NAFLD is a metabolic disorder and considered to be the hepatic manifestation of the metabolic syndrome. The precise pathophysiological mechanisms underlying the development of NAFLD are not fully clarified, but multifactorial contributors including environmental factors (diet, sedentary lifestyle, low levels of physical activity), central obesity, insulin resistance, alterations in gut microbiota and (epi)genetic factors are likely to play an important role [1]. As a result of the global obesity epidemic, NAFLD is an increasingly relevant public health issue, with major clinical and economic impact on society, and where it is estimated that 22% of the Northern Dutch population and globally nearly 1 billion people are affected [2,3,4]. The spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and ultimately cirrhosis [1,5]. A substantial proportion of the population has NAFLD, but only a minority progresses to advanced liver disease. NASH is seen as a progressive and severe form of NAFLD and can only be diagnosed by histology. There is however a paucity of studies with reliable prevalence data. By extrapolation of data from available liver biopsy studies from 22 countries it is estimated that NASH is present in 2.5-5% of the population [6]. These data are very crude estimates and accurate prevalence data are absent, certainly for the Netherlands. This data is however highly relevant because approximately 40% of NASH patients will develop progressive fibrosis and eventually cirrhosis, accompanied by high morbidity and mortality [6]. While epidemiological data suggests that NASH is very common in the Western population, a deep granular map of NASH in the Netherlands is absent. A better understanding of the prevalence of NASH is needed to identify risk factors that contribute to the development of NASH. Knowledge about these risk factors can help in differentiating which NAFLD patients will progress towards NASH and progressive cirrhosis, opening up possibilities for early intervention.

Research question / problem definition
Primary objectives: - To map the epidemiology of NAFLD, NASH and NASH-fibrosis. - To identify risk factors for the development of advanced fibrosis in NASH. Secondary objectives: - To evaluate the performance of non-invasive scoring systems that predict the presence of fibrosis in NASH. - To evaluate the performance of transient elastography (Fibroscan) in this population

Workplan
Retrospective cohort study (medical records) of patients with a confirmed diagnosis of NAFLD or NASH based upon histological criteria for NAFLD in liver biopsies (previously established through PALGA and confirmed by an independent pathologist).

References

1. Arab JP, Arrese M, Trauner M. Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease. Annual Review of Pathology 2018;13:321–50.
2. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology (Baltimore, Md) 2015.
3. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nature Reviews Gastroenterology & Hepatology 2018;15:11–20.
4. van den Berg EH, Amini M, Schreuder TC, Dullaart RP, Faber KN, Alizadeh BZ, et al. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort. PloS one. 2017;12(2):e0171502.
5. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nature Reviews Gastroenterology & Hepatology 2013;10:686–90.
6. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology (Baltimore, Md). 2016;64(1):73-84.

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