Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related 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.

Pathogenesis and significance of hepatitis C virus steatosis:An update on survival strategy of a successful pathogen

Hepatitis C virus(HCV)is a successful pathogen on the grounds that it exploits its host’s metabolism to build up viral particles;moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ.Steatosis,therefore,is associated with HCV infection by necessity rather than by chance alone.Approximately6%of HCV patients have steatohepatitis.Interestingly,HCV steatosis occurs in the setting of multiple metabolic abnormalities(hyperuricemia,reversible hypocholesterolemia,insulin resistance,arterial hypertension and expansion of visceral adipose tissue)collectively referred to as"hepatitis C-associated dysmetabolic syndrome"(HCADS).General,nonalcoholic fatty liver disease(NAFLD)-like,mechanisms of steatogenesis(including increased availability of lipogenic substrates and de novo lipogenesis;decreased oxidation of fatty substrates and export of fatty substrates)are shared by all HCV genotypes.However,genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein;peroxisome proliferator-activated receptor alpha;sterol regulatory element-binding proteins and phosphatase and tensin homologue.HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis;for impaired treatment response to interferon and ribavirin;and development of hepatocellular carcinoma.Recent data,moreover,suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms.In conclusion,HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle.A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.

Fatty liver,carotid disease and gallstones:A study of age-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 disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined. RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD. Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings. CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.

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 T2 D 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 T2 D 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 T2 D 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.

Clinical features and natural history of cryptogenic cirrhosis compared to hepatitis C virus-related cirrhosis

AIM To characterize natural history of cryptogenic cirrhosis(CC) and compare its clinical features and outcomes to those of hepatitis C virus(HCV)-related cirrhosis.METHODS A prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an ageand Child-pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were:(1) severity of liver disease at the time of first diagnosis;(2) liver decompensation during follow-up;(3) hepatocellular carcinoma(HCC);(4) orthotopic liver transplantation; and(5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression.RESULTS At the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome(12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Childpugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-pugh class A.CONCLUSION Undiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer.

Sex disparity in hepatocellular carcinoma owing to NAFLD and non-NAFLD etiology:epidemiological findings and pathobiological mechanisms

Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk factors.NAFLD is now projected to become the most common cause of HCC.HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio.In this review article,we focus on sex differences in the epidemiological features of HCC.Moreover,we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC.By highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.