Fatty liver disease

A progressive and potentially life-threatening condition previously associated with alcoholism is becoming more common — even in non-drinkers.

Increased levels of obesity are driving an epidemic of non-alcoholic fatty liver disease. Understanding, diagnosing and treating this progressive condition are now priorities.

NAFLD is growing in prevalence worldwide, and has emerged as a leading cause of end-stage liver disease in many countries. In this Review, the authors describe the global epidemiology of NAFLD, discuss associated risk factors and outline challenges for screening and management.

In a new study, Younossi et al. poignantly depict the daunting and enormous prevalence of NAFLD and its associated clinical and economic burden in the USA and four countries in Europe. The astronomical health-care costs will increase as the prevalence of NAFLD increases. All stakeholders are called to action.

A recent study reports that being overweight in late adolescence is associated with an increased risk of liver-related morbidity and mortality later in life. These findings give further strength to the concerns for the deleterious effects of childhood obesity on liver health. Early prevention by screening and lifestyle modification should be advised by health policies.

NAFLD, the hepatic manifestation of the metabolic syndrome, is a multifactorial condition — environmental factors influence an inherited genetic risk. Stender et al. now describe the additive effect of obesity and NAFLD-associated genetic polymorphisms on steatosis, elevated serum alanine aminotransferase levels and cirrhosis, remarkably illustrating the principle of gene–environment interactions.

Current mouse models of nonalcoholic steatohepatitis are limited, making identification and preclinical testing of new treatments challenging. Housing mice at thermoneutrality leads to less stress, a stronger immune response and better modeling of this condition.

Non-alcoholic fatty liver disease (NAFLD) is shown to promote hepatocellular carcinoma through the generation of linoleic acid, disruption of mitochondrial function and selective loss of CD4⁺ T cells, leading to impaired anti-tumour immunity.

This Review discusses the mechanisms via which changes in the gut can influence the development and progression of NAFLD. Understanding of such mechanisms is hoped to pave the way for new treatments for what has become the most common form of liver disease.

The association between NAFLD and diabetes mellitus has garnered increasing attention in the past few years. In this Review, Tilg and colleagues explore in detail the molecular mechanisms linking NAFLD and diabetes mellitus, and discuss clinical aspects arising from the interaction of both diseases.

Nonalcoholic fatty liver disease is characterized by excess accumulation of fat in hepatocytes, which can be accompanied by inflammation, cell injury and fibrosis. Here, Brunt et al. explain the pathophysiology, the current limitations in management options and the avenues for progress.