Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


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

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  1. 1.

    Younossi, Z. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 15, 11–20 (2018).

    Article  Google Scholar 

  2. 2.

    Liu, D. et al. Squalene epoxidase drives NAFLD-induced hepatocellular carcinoma and is a pharmaceutical target. Sci. Transl Med. 10, eaap9840 (2018).

    Article  Google Scholar 

  3. 3.

    Abul-Husn, N. S. et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N. Engl. J. Med. 378, 1096–1106 (2018).

    CAS  Article  Google Scholar 

  4. 4.

    Hoyles, L. et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat. Med. 24, 1070–1080 (2018).

    CAS  Article  Google Scholar 

  5. 5.

    European Association for the Study of the Liver, European Association for the Study of Diabetes & European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol. 64, 1388–1402 (2016).

    Google Scholar 

  6. 6.

    Dibba, P. et al. Emerging therapeutic targets and experimental drugs for the treatment of NAFLD. Diseases 6, E83 (2018).

    Article  Google Scholar 

  7. 7.

    Arab, J. P. et al. Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives. Hepatology 65, 350–362 (2017).

    Article  Google Scholar 

  8. 8.

    Zhou, M. et al. Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis. Nat. Commun. 8, 15433 (2017).

    CAS  Article  Google Scholar 

  9. 9.

    Harrison, S. A. et al. NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 391, 1174–1185 (2018).

    CAS  Article  Google Scholar 

Download references


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.

Author information



Corresponding author

Correspondence to Elisabetta Bugianesi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Younes, R., Bugianesi, E. A spotlight on pathogenesis, interactions and novel therapeutic options in NAFLD. Nat Rev Gastroenterol Hepatol 16, 80–82 (2019).

Download citation

Further reading


Quick links