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Review
. 2022 May 5;23(9):5146.
doi: 10.3390/ijms23095146.

Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis

Marija Branković  1   2 , Igor Jovanović  1 , Marija Dukić  1 , Tijana Radonjić  1 , Svetlana Oprić  1 , Slobodan Klašnja  1 , Marija Zdravković  1   2
Affiliations
Review

Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis

Marija Branković et al. Int J Mol Sci. .

Abstract

The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible.

Keywords: NAFLD; NASH; lipids; liver; metabolism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Diagnosis, treatment, risk factors, and cardiovascular consequences of non-alcoholic steatohepatitis.
Figure 1
Figure 1
Liver biopsy of non-alcoholic steatohepatitis (NASH) stage 3 (severe fibrosis). Portal spaces are normal size or slightly dilated, connected by septa of connective tissue that sometimes surround parenchymal nodules. They are moderately to strongly infiltrated with lymphocytes and rare granulocytes. The parenchyma is partially nodularly transformed, and rare focal necrosis is present. Hepatocyte joists are focally thickened. Focal glycogenization of hepatocyte nuclei is present. Ballooned hepatocytes are numerous. Coarse-grained fatty change is diffuse. Kupffer cells multiply in the sinuses. There are numerous foci of perisinusoid necrosis. Hematoxylin and eosin (H&E) staining, 10 × Legend: 1, lymphocytes; 2, focal necrosis; 3, ballooned hepatocytes; 4, fat accumulation; 5, Kupffer cells.
Figure 2
Figure 2
NASH treatment options.
See this image and copyright information in PMC

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