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NAFLD IN 2018

A spotlight on pathogenesis, interactions and novel therapeutic options in NAFLD

Nature Reviews Gastroenterology & Hepatology volume 16, pages 80–82 (2019)Cite this article

Subjects

In 2018, there have been substantial advances in our understanding of the risk factors for advanced liver disease in nonalcoholic fatty liver disease, including genetic variants and the gut microbiota. Promising results have also arisen from drugs targeting metabolic pathways involved in the progression of liver damage.

Key advances

  • Squalene epoxidase (SQLE) has a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma, and drugs targeting SQLE (such as terbinafine) might be considered for the treatment of this cancer2.

  • A splice variant in HSD17B13 is associated with reduced levels of liver transaminases and reduced risk of nonalcoholic steatohepatitis (NASH), fibrosis and NAFLD-related cirrhosis3.

  • Patients with NAFLD have low microbial gene richness and increased microbial genetic potential for the processing of dietary lipids and endotoxin biosynthesis, leading to hepatic inflammation and amino acid biosynthesis dysregulation4.

  • Results of the phase 2 study testing the safety and efficacy of NGM282, a non-tumorigenic analogue of fibroblast growth factor 19, revealed NGM282 was able to reduce liver-fat content, inflammation and fibrosis in patients with biopsy-proven NASH9.

Nonalcoholic fatty liver disease (NAFLD) is the new frontier in liver disease; the condition is now the leading aetiology of chronic hepatitis in the Western world and the only one for which global prevalence is steadily rising over time, particularly in developing countries (for example the Middle East or South America)1. Up to 15% of patients with NAFLD will develop the active form of the disease, nonalcoholic steatohepatitis (NASH), which is characterized by the three histological hallmarks of steatosis, lobular inflammation and hepatocyte ballooning in the absence of clinically significant alcohol intake (defined as <2 drinks per day)1. Patients with NASH can progress to fibrosis, cirrhosis and hepatocellular carcinoma (HCC) and have an increased likelihood of liver-related mortality, which is the third highest cause of death in these individuals compared with the thirteenth highest in the general population1.

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Fig. 1: Crosstalk between NAFLD pathogenesis and treatment in 2018.

References

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Acknowledgements

R.Y. and E.B. are supported by grant from the EPoS (Elucidating Pathways of Steatohepatitis) consortium funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413.

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  1. Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy

    Ramy Younes & Elisabetta Bugianesi

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  1. Ramy Younes
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  2. Elisabetta Bugianesi
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Correspondence to Elisabetta Bugianesi.

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Younes, R., Bugianesi, E. A spotlight on pathogenesis, interactions and novel therapeutic options in NAFLD. Nat Rev Gastroenterol Hepatol 16, 80–82 (2019). https://doi.org/10.1038/s41575-018-0094-6

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