Abstract
The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved.
Highlights
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, insulin resistance (IR) and type 2 diabetes (T2D)
Substantial evidence suggests that NAFLD and Hepatitis C virus (HCV) play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications
Non-alcoholic fatty liver disease (NAFLD) describes a cluster of hepatic disorders predominantly characterized by fatty changes with or without ballooning degeneration and fibrosis (i.e., simple steatosis, steatohepatitis (NASH) and advanced fibrosis), which may evolve into cirrhosis (NASH-cirrhosis will typically lose fatty changes) and hepatocellular carcinoma (HCC); NAFLD is commonly observed in insulin-resistant, dysmetabolic individuals without excessive alcohol consumption and other competing etiologies of liver disease [3,4]
Summary
Non-alcoholic fatty liver disease (NAFLD) describes a cluster of hepatic disorders predominantly (though not exclusively) characterized by fatty changes with or without ballooning degeneration and fibrosis (i.e., simple steatosis, steatohepatitis (NASH) and advanced fibrosis), which may evolve into cirrhosis (NASH-cirrhosis will typically lose fatty changes) and hepatocellular carcinoma (HCC); NAFLD is commonly observed in insulin-resistant, dysmetabolic individuals without excessive alcohol consumption and other competing etiologies of liver disease [3,4]. There is compelling evidence that NAFLD is a multisystem disease associated with a wide range of extra-hepatic manifestations, notably including, among others, IR, dysglycemia and premature atherosclerosis [5,6]. To NAFLD, HCV infection is increasingly identified as a systemic disease which may be conducive to metabolic disorders (including IR and T2D) and premature atherosclerosis [8]
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