Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV

Abstract

Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

Keywords: Atherosclerosis; Cardiovascular risk; Fatty liver; Fibrosis; Hepatitis C virus; Hepatitis C-associated dysmetabolic syndrome; Human immunodeficiency virus; Nonalcoholic fatty liver disease; Steatohepatitis; Steatosis; Virus-associated fatty liver disease.

Figure 1

Mechanisms underlying type 2 diabetes and cardiovascular disease in nonalcoholic fatty liver disease and virus-associated fatty liver disease. This cartoon schematically depicts the nonalcoholic fatty liver disease (NAFLD)-derived paradigm supporting a link between NAFLD and the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Based on this model, the presence of NAFLD per se plays a role in the pathogenesis of these two cardiometabolic complications. This possibly occurs through the systemic release of several pro-inflammatory/pro-coagulant mediators from the steatotic/inflamed/fibrotic liver or through the contribution of NAFLD itself to insulin resistance and atherogenic dyslipidaemia. Virus-associated fatty liver disease (VAFLD) identifies fatty liver associated with either chronic HCV or HIV infections. The novel comparative data presented in this review support the assertion that VAFLD conceptually mimics NAFLD and thus might partly contribute (along with specific viral factors related to HCV and HIV) to the pathogenesis of T2D and CVD also in this group of patients. The putative pathogenic mechanisms illustrated in the right hand side of the figure have been predominantly shown in NAFLD[37,104] and, by inference, should also be investigated in VAFLD.