The Association of Non Viral Liver Diseases from NAFLD to NASH to HCC with the Pandemic of Obesity, Type 2 Diabetes, or Diabesity & Metabolic Syndrome Etiopathogenetic Correlation along with Utilization for Diagnostic & Therapeutic Purposes-A Systematic Review

Abstract
Earlier we have been reviewing the etiopathogenesis (EP) of obesity, type2 Diabetes mellitus (T2DM), Metabolic Syndrome (MetS), Non Alcoholic Fatty Acid Liver Disease (NAFLD) non alcoholic steatohepapititis (NASH), along with its propagation to Hepatocellular carcinoma (HCC) in addition to their therapies exhaustively. T2DM continues to be a major health issue with reaching epidemic to pandemic proportions. Liver disease includes a spectrum of liver injury varying from isolated steatosis known as Non Alcoholic Fatty Acid Liver Disease (NAFLD) to HCC. Clinically it has been observed that the coexistence of NAFLD as well as T2DM is prevalent. T2DM aids in the biological events that results in escalation of robustness of NAFLD that constitutes the primary etiology of chronic liver diseases. In the past 2 decades the incidence of nonviral NAFLD/NASH, obtained HCC has been escalating at a fast pace. In view of no appropriate agents for therapy of NAFLD/NASH, a thiazolidenedione group of drug pioglitazone used for T2DM therapy is utilized occasionally.Thus here we conducted a systematic review utilizing search engine pubmed, google scholar; web of science; embase; Cochrane review libraryutilizingtheMeSHterms like T2DM; MetS; NAFLD; NASH; HCC;WAT; BAT; VisceralAT; Obesity; BMI; Adipocytokines; adiponectin;leptin; resistin; visfatin; irisin; Hepatokines; angiopoietin like protein 2; hepatosscin; retinol binding protein 4; treatment like pioglitazone;liraglutide; elafibranor CVC (cerviciroc); obeticholic acid; aramchol;selonosertib; simtuzumab; Oxidative stress(OS); insulin resistance (IR) from 1980’s to 2021 till date. We found a total of 1050 articles out of which we selected 236 articles for this review. No meta-analysis was done. Hence diagnosis avoidance in addition to treatment of the generation as well as propagation of NAFLD/NASH are significant areas needing tackling. Thus here we have summarized the EP of NAFLD/NASH, as well as NAFLD/NASH, obtained HCC along with the present advantageous therapies under trial,for NAFLD/NASH. Moreover how adipocyte obtained adipokines along with liver obtained hepatokines might work as both diagnostic in addition to therapeutic targets from NAFLD to HCC.