Diabetes Metab J.  2024 Mar;48(2):161-169. 10.4093/dmj.2023.0240.

Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome

• Friedman SL

• KMID: 2553587
• DOI: http://doi.org/10.4093/dmj.2023.0240

Abstract

Metabolic dysfunction-associated steatotic (fatty) liver disease (MASLD), previously termed non-alcoholic fatty liver disease, is a worldwide epidemic that can lead to hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The disease is typically a component of the metabolic syndrome that accompanies obesity, and is often overlooked because the liver manifestations are clinically silent until late-stage disease is present (i.e., cirrhosis). Moreover, Asian populations, including Koreans, have a higher fraction of patients who are lean, yet their illness has the same prognosis or worse than those who are obese. Nonetheless, ongoing injury can lead to hepatic inflammation and ballooning of hepatocytes as classic features. Over time, fibrosis develops following activation of hepatic stellate cells, the liver’s main fibrogenic cell type. The disease is usually more advanced in patients with type 2 diabetes mellitus, indicating that all diabetic patients should be screened for liver disease. Although there has been substantial progress in clarifying pathways of injury and fibrosis, there no approved therapies yet, but current research seeks to uncover the pathways driving hepatic inflammation and fibrosis, in hopes of identifying new therapeutic targets. Emerging molecular methods, especially single cell sequencing technologies, are revolutionizing our ability to clarify mechanisms underlying MASLD-associated fibrosis and HCC.

Keyword

Carcinoma, hepatocellular; Diabetes mellitus, type 2; Extracellular matrix; Fibrosis; Hepatic stellate cells; Liver diseases; Liver neoplasms; Republic of Korea

Figure

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  Fig. 1. Hepatic drivers of MASLD and fibrosis. A number of upstream signals converge on hepatocytes to induce injury, combined with dysregulated immunity and insulin resistance. These lead to hepatocyte-derived molecules that activate hepatic stellate cells and amplify inflammation. Within activated stellate cells, a number of intracellular changes contribute to progressive fibrosis. IGF1, insulin like growth factor 1; ER, endoplasmic reticulum.

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