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Editorial
. 2020 Apr;9(2):230-234.
doi: 10.21037/hbsn.2019.10.09.

Diabetes is associated with increased risk of hepatocellular carcinoma in non-alcoholic steatohepatitis with cirrhosis-implications for surveillance and future pharmacotherapy

Michael P Johnston  1 , Janisha Patel  1 , Christopher D Byrne  2   3
Affiliations
Editorial

Diabetes is associated with increased risk of hepatocellular carcinoma in non-alcoholic steatohepatitis with cirrhosis-implications for surveillance and future pharmacotherapy

Michael P Johnston et al. Hepatobiliary Surg Nutr. 2020 Apr.
No abstract available

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn.2019.10.09). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Mechanistic pathways associated with promotion of hepatocarcinogenesis in T2DM. T2DM is associated with an increased risk of NASH. NASH is associated with a progressive process of collagen deposition and fibrogenesis. This inflammatory process drives hepatocellular DNA damage, endoplasmic reticulum stress and hepatocellular necrosis leading to regenerative nodule formation, dysplastic nodules and ultimately carcinoma. Unhealthy diet and T2DM-related dysbiosis within the gut are associated with loss of intestinal integrity and altered levels of SCFAs. Due to loss of intestinal integrity there is translocation of pro-inflammatory bacterial components such as LPS across the gut wall, which activates TLR-4 receptors. There is evidence that TLR-4-dependent secretion of growth factors, including epiregulin, mediate a hepatocarcinogenic effect (11). Butyrate is a SCFA that upregulates apoptosis in the liver via modulation of ROS. The alteration in levels of SCFAs, including butyrate, is associated with reduced apoptosis and increased steatosis, cholestasis and hepatocarcinogenesis (12). In the presence of insulin resistance and NASH there is also a reduction in levels of IGF-1 (13). Alteration in IGF-1 levels may dysregulate immune response by HSCs, predisposing to hepatocellular proliferation and hepatocarcinogenesis. Insulin appears to stimulate HSCs collagen deposition. T2DM, type 2 diabetes mellitus; NASH, non-alcoholic steatohepatitis; SCFA, short chain fatty acid; LPS, lipopolysaccharide; TLR-4, toll-like receptor 4; ROS, reactive oxygen species; IGF-1, insulin-like growth factor 1; HSC, hepatic stellate cell; HCC, hepatocellular carcinoma.
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Comment on

References

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