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

  title={From NAFLD to NASH to cirrhosis—new insights into disease mechanisms},
  author={Alexander Wree and Lori Broderick and Ali Canbay and Hal M Hoffman and Ariel E. Feldstein},
  journal={Nature Reviews Gastroenterology \&Hepatology},
NAFLD has evolved as a serious public health problem in the USA and around the world. In fact, NASH—the most serious form of NAFLD—is predicted to become the leading cause of liver transplantation in the USA by the year 2020. The pathogenesis of NAFLD and NASH, in particular the mechanisms responsible for liver injury and fibrosis, is the result of a complex interplay between host and environmental factors, and is at the centre of intense investigation. In this Review, we focus on recently… 

Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases

The current epidemiology, diagnosis, animal models, pathogenesis, and treatment strategies for NAFLD are comprehensively reviewed, emphasizing the outstanding breakthroughs in the above fields and promising medications in and beyond phase II.

The genetics of NAFLD

The current status of the field is described, discussing specific genetic and epigenetic modifiers, including the mechanisms through which genes identified by genome-wide association studies, including PNPLA3, influence disease progression.

Pathogenesis of Nonalcoholic Steatohepatitis and Hormone-Based Therapeutic Approaches

Current findings and knowledge regarding the pathogenesis of NASH are reviewed, focusing on the most recent advances and hormone-based therapeutic approaches for treatment ofNASH are highlighted.

Evolving therapies for non-alcoholic steatohepatitis

Treatment of NAFLD is still in its infancy, although large controlled studies have demonstrated some efficacy for pioglitazone or vitamin E, and the authors highlight the current most promising treatment strategies in NASH/NAFLD.

A Review of Pharmacological Treatments of NASH

A clinical review of the pharmacological treatment of NASH in the last years due to the increasing incidence of NAFLD and NASH around the world and the long term safety of several agents remain to be established.

NASH and the Cross-Talk Between the Gut and Liver

An overview of the current knowledge on the pathophysiology of the cross-talk between the gut and the liver in the pathogenesis of NAFLD and its progression to NASH is provided, and potential therapeutic means to manipulate the intestinal microbiota in order to modulate liver disease development are discussed.

Steatosis and Steatohepatitis: Complex Disorders

An overview about the currently available knowledge and recent findings regarding the development and progression of non-alcoholic fatty liver disease is given.

Macrophage Function in the Pathogenesis of Non-alcoholic Fatty Liver Disease: The Mac Attack

The current understanding of the cellular and molecular processes that govern macrophage contribution to NAFLD pathogenesis and how adipose tissue and liver crosstalk modulates macrophages function are reviewed to lead to the development of new therapies forNAFLD.

Importance of iron overload and steatosis in patients with chronic liver disease

An increased number of regulatory T-cells and CD68 cells in NASH, pointing at an involvement of both the adaptive and innate immune systems, and the association between hepcidin and iron parameters, lipid status and inflammatory markers in NAFLD in relation to other chronic liver diseases.

The Role of Cholesterol in the Pathogenesis of NASH

  • G. Ioannou
  • Medicine, Biology
    Trends in Endocrinology & Metabolism
  • 2016



The epidemiology of nonalcoholic fatty liver disease: a global perspective.

The burden of NAFLD is expected to increase in years to come as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B.

Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis

Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.

Good fat/bad fat

A more complex model of steatosis was used, employing db/db mice fed a methionine-restricted, choline-deficient (MCD) diet, and there was some optimism that blocking DGAT2, which catalyzes the final step in hepatic triglyceride production, may be beneficial in NAFLD/NASH.

Obesity Affects the Liver – The Link between Adipocytes and Hepatocytes

This review summarizes current knowledge – highlighting the inflammatory and cytokine view – of the intimate relationship between adipose and liver tissue and suggests reduced adiponectin levels may establish a proinflammatory milieu, thus increasing vulnerability to lipotoxicity.

Non‐alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis

NAFLD/NASH as the hepatic entity of the MS may itself pose a risk factor for HCC, even in the absence of cirrhosis, and increased awareness of liver manifestations in theMS may instigate early interventions against developing HCC.

Mechanisms of hepatic fibrogenesis.

Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease.

Inflammasomes in liver diseases.