Dramatic changes in the lifestyle and diet of the global population are fuelling the worldwide epidemic of obesity and the increasing prevalence of NAFLD, in which fatty deposits in the liver cause a wide spectrum of disease—from simple steatosis, through to NASH, fibrosis and cirrhosis, which can result in liver cancer and end-stage liver disease. Notably, experts now predict that the next epidemic of chronic liver disease worldwide will be a direct result of obesity and NAFLD, with NAFLD replacing viral hepatitis as the primary cause of end-stage liver disease and liver transplantation. Already an estimated one in three individuals in the USA and one in five individuals in the UK are thought to have a fatty liver, with rising incidence also observed in children.

This special Focus on NAFLD from Nature Reviews Gastroenterology & Hepatology brings together key experts to provide a comprehensive overview of the most important topics in the field, providing a valuable resource for the hepatology community. The Focus covers the breadth of basic, translational and clinical research. Seven specially commissioned articles—six Reviews and one Perspective—highlight new understanding of the pathogenesis of NAFLD (including the role of the gut microbiota and how NAFLD can progress to liver cancer), practical insights into noninvasive diagnosis of NAFLD and pharmacological agents available to treat the disease, as well as discussion of the global NAFLD epidemic and the future research agenda.


NAFLD—the next global epidemic

Katrina Ray


Nature Reviews Gastroenterology & Hepatology 10, 621 (2013)


From NAFLD to NASH to cirrhosis—new insights into disease mechanisms

Alexander Wree, Lori Broderick, Ali Canbay, Hal M. Hoffman & Ariel E. Feldstein


Nature Reviews Gastroenterology & Hepatology 10, 627-636 (2013)

Here, the authors summarize new insights into the pathogenesis of NAFLD and NASH, in particular the mechanisms responsible for liver injury and fibrosis. They highlight how a complex interplay between the environment (especially diet), host genetics and the gut microflora is crucial for the development and progression of NAFLD.

The Gordian Knot of dysbiosis, obesity and NAFLD

Wajahat Z. Mehal


Nature Reviews Gastroenterology & Hepatology 10, 637-644 (2013)

The development of obesity and NAFLD is known to be determined by host genetics, diet and lack of exercise. In addition, the gut microbiota has been shown to influence the development of both of these conditions. In this Review, current understanding of the relationship between the intestinal microbiota, obesity and NAFLD is discussed, with an emphasis on causal relationships, latest advances and therapeutic opportunities.

The genetics of NAFLD

Quentin M. Anstee & Christopher P. Day


Nature Reviews Gastroenterology & Hepatology 10, 645-655 (2013)

NAFLD is a complex disease. Considerable variability exists in the severity and risk of morbidity and mortality among individuals with NAFLD, which could be influenced by genetic and environmental factors. Here, the authors discuss the latest knowledge on the genetics of NAFLD and how this genetic variation might determine disease phenotype and progression.

NAFLD, NASH and liver cancer

Gregory A. Michelotti, Mariana V. Machado & Anna Mae Diehl


Nature Reviews Gastroenterology & Hepatology 10, 656-665 (2013)

The incidence of NAFLD, which increases the risk of liver cancer, is increasing to epidemic proportions. This Review outlines the correlations between liver cancer and NAFLD-related cirrhosis, and the role of the metabolic syndrome in the development of liver cancer. Advances in understanding the progression of NAFLD to hepatocellular carcinoma from preclinical models will also be discussed.

Noninvasive evaluation of NAFLD

Laurent Castera, Valérie Vilgrain & Paul Angulo


Nature Reviews Gastroenterology & Hepatology 10, 666-675 (2013)

Accurate diagnosis and staging of NAFLD is of utmost prognostic importance. The gold standard for diagnosis is histological examination, but growing interest exists in novel noninvasive methods to evaluate NAFLD. This Review describes the advantages and limitations of noninvasive methods for the diagnosis and quantification of steatosis, diagnosis of NASH and staging of hepatic fibrosis in NAFLD.

Pharmacological agents for NASH

Vlad Ratziu


Nature Reviews Gastroenterology & Hepatology 10, 676-685 (2013)

Optimal management of NASH is required because the condition can progress to cirrhosis and end-stage liver failure. Once first-line therapy with diet and lifestyle changes has failed, pharmacological intervention is indicated. This Review discusses the available evidence from clinical trials on pharmacological agents for NASH.


The global NAFLD epidemic

Rohit Loomba & Arun J. Sanyal


Nature Reviews Gastroenterology & Hepatology 10, 686-690 (2013)

Global differences in the prevalence and presentation of NAFLD are presented in this Perspectives article. The authors also convey how scientific advances in our understanding and management of NAFLD now need to be translated to improve awareness at the level of society, influence global health policy and research priorities and ensure a better future for our coming generations.

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