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

Fatty liver, which frequently coexists with necroinflammatory 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

Sofosbuvir-based therapy cures hepatitis C virus infection after prior treatment failures in a patient with concurrent lymphoma

We report on the first well-tolerated and successful use of sofosbuvir-based therapy in a patient in whom chronic infection with hepatitis C had preceded the development of B-cell non-Hodgkin's lymphoma. The patient had previously failed numerous attempts to clear the hepatitis C virus with traditional antiviral schedules. We demonstrate that sofosbuvir-based therapy resulted in cure of hepatitis C in a patient who had relapsed during combination therapy with an NS5A inhibitor, an NS3 protease inhibitor and ribavirin, as well as treatment failures to multiple courses of interferon-based therapy. This report also suggests that eradication of hepatitis C virus may result in the short-term prevention of B-cell non-Hodgkin's lymphoma relapse. The findings from our case require further validation in future cohorts of patients

The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans.

Nonalcoholic fatty liver disease (NAFLD) describes steatosis, nonalcoholic steatohepatitis with or without fibrosis, and hepatocellular carcinoma, namely the entire alcohol-like spectrum of liver disease though observed in the nonalcoholic, dysmetabolic, individual free of competing causes of liver disease. NAFLD, which is a major public health issue, exhibits intrahepatic triglyceride storage giving rise to lipotoxicity. Nuclear receptors (NRs) are transcriptional factors which, activated by ligands, are master regulators of metabolism and also have intricate connections with circadian control accounting for cyclical patterns in the metabolic fate of nutrients. Several transcription factors, such as peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptors, and their molecular cascades, finely regulate energetic fluxes and metabolic pathways. Dysregulation of such pathways is heavily implicated in those metabolic derangements characterizing insulin resistance and metabolic syndrome and in the histogenesis of progressive NAFLD forms. We review the role of selected NRs in NAFLD pathogenesis. Secondly, we analyze the role of NRs in the natural history of human NAFLD. Next, we discuss the results observed in humans following administration of drug agonists or antagonists of the NRs pathogenically involved in NAFLD. Finally, general principles of treatment and lines of research in human NAFLD are briefly examined

"Not all forms of NAFLD were created equal". Do metabolic syndrome-related NAFLD and PNPLA3-related NAFLD exert a variable impact on the risk of early carotid atherosclerosis?

On this background of evidence, the results of the study by Di Costanzo et al. [8] provide further support to the view that the aetiology of NAFLD is multifactorial and this disease may be caused by common genetic variants. One of these, the PNPLA-3 variant, is associated with higher liver fat content and increased risk of NASH, but is not systematically associated with insulin resistance and MetS traits [4,5]. This study adds a further critical piece of information by suggesting that the MetS-related NAFLD and the PNPLA3-related NAFLD may differentially affect the risk of subclinical atherosclerosis and perhaps of clinical CVD [8]. However, it does not detract from the notion that NAFLD, especially NASH with varying degrees of fibrosis, may directly contribute to the development and progression of CVD [2,3,9], because genetic NAFLD is a subtly different disease and less than 15% of European patients with NAFLD have the PNPLA3 GG genotype [4,5]. Furthermore, as previously mentioned, the few observational studies that have assessed the association between the PNPLA3 rs738409 gene polymorphism and risk of atherosclerosis have provided conflicting results (as summarized in Table 1

Cardiovascular Disease and Myocardial Abnormalities in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in many developed countries, affecting an estimated 30 % of the adult population. In this updated clinical review, we summarize the current knowledge regarding the strong association between NAFLD and the risk of coronary heart disease (CHD) and other functional, structural, and arrhythmic cardiac complications (e.g., left ventricular dysfunction, heart valve diseases and atrial fibrillation). We also briefly discuss the putative biological mechanisms linking NAFLD with these important extra-hepatic complications. To date, a large body of evidence has suggested that NAFLD is not simply a marker of CHD and other functional, structural, and arrhythmic cardiac complications, but also may play a part in the development and progression of these cardiac complications. The clinical implication of these findings is that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions aimed at decreasing the risk of CHD and other cardiac and arrhythmic complications

Nonalcoholic fatty liver disease and aging: epidemiology to management

Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients

Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in Symptomatic Coronary Artery Disease and Peripheral Arterial Disease?

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with both atherosclerotic cardiovascular disease (CVD) and Fetuin-A. However, the association of Fetuin-A with atherosclerosis is more controversial. We hypothesized that the pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis varies based on arterial site. Accordingly, we aimed to assess NAFLD prevalence, Fetuin-A values and their relationship with symptomatic atherosclerosis occurring in different localizations: coronary artery disease (CAD) vs. peripheral arterial disease (PAD)

Relationship of Serum Fetuin-A Levels with Coronary Atherosclerotic Burden and NAFLD in Patients Undergoing Elective Coronary Angiography

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Fatty liver, carotid disease and gallstones: A study ofage-related associations

AIM: To evaluate carotid intima-media thickening (IMT)and plaques, gallstone disease (GD) and fatty liver (FL)as a function of age.METHODS: In 449 subjects, FL and carotid diseasewere assessed ultrasonographically. In a subgroup of65/449 patients with non-alcoholic fatty liver disease(NAFLD), carotid disease, GD and associated factorswere determined.RESULTS: FL of unspecifi ed etiology was more commonin younger and GD in older individuals. FL subjectshad an increased prevalence of IMT and a decreasedprevalence of plaques and manifested carotid diseaseearlier. Plaques were more common in subjects with GD.Age was an independent predictor of carotid diseaseoutcome and FL was a protective factor for plaques. InNAFLD, there was an inverse correlation between bodyweight and age and the latter independently predictedcarotid fi ndings.CONCLUSION: Cardiovascular risk in patients with FLand NAFLD needs to be assessed as a function of ageand body weight