An Update on the Etiopathogenesis of NAFLD including Organokines for Early Diagnosis and Improvement of Management and Preventing Early HCC Development: A Narrative Review

Abstract

Background
Earlier, we reviewed different methods of treating non-alcoholic fatty acid liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), concentrated on organokines liberated by adipose tissue (AT) and liver (adipoklines and hepatokines), adipokines 
in obesity with heart failure (HF), and myokines like irisin in exercise in obesity, and thought they might work as diagnostic and 
therapeutic targets in NAFLD and NASH with hepatocellular carcinoma (HCC). These are believed to be biological markers that 
can anticipate the robustness of NAFLD from NAFLD to HCC. 
Methods
We conducted a narrative review utilizing search engines PubMed, Google Scholar; Web of Science; Embasee; Cochrane Library 
utilizing the MeSH terms “NAFLD”; “NASH”; “Organokines”; “Adipokines”; “Hepatokines”; “Myokines”; “Osteokines”; “Stellakines”; 
“Fructose”; “Gut Microbiota”; “Insulin resistance (IR)”; “Crosstalk of organokines”; “Obesity”; “T2D” from last 10-years till date in 2023.
Results
We found a total of 750 articles, out of which we selected 95 for this review. No meta-analysis has been done.
Conclusion
As acknowledged earlier, NAFLD possesses the characteristics of simple steatosis, while NASH progresses to hepatic steatosis, 
lobular inflammation, and an escalated diameter of hepatocytes (ballooning of hepatocytes) with or without fibrosis in 20% of 
cases of NAFLD. Usually, it is correlated with metabolic diseases like obesity, type 2 diabetes mellitus (T2DM), and metabolic 
syndrome (MetS); hence, the liberation of organokines gets manipulated in a way that might aid in the etiopathogenesis or propagation of disease. We observed that insulin resistance (IR), oxidative stress (OS), mitochondrial impairment, fructose, and gut 
microbiota reflected factors taking part in the development and propagation of NASH. Alterations in various organokines (inclusive of adipokines, hepatokines, myokines, osteokines, and a newer one, stellakines) produced by hepatic stellate cells (HSCs) 
were further seen to directly or indirectly aid in the exacerbation and propagation of disease or cause dysfunctional homeostasis. 
Moreover, we discuss the role of stellakines in detail, and targeting silymarin might give us an efficacious drug for the early treatment of NAFLD or NASH.