Nonalcoholic fatty liver disease (NAFLD) – Is it a new marker of hyporesponsiveness to recombinant human erythropoietin in patients that are on chronic hemodialysis?

Anemia is a major consequence of chronic kidney disease (CKD) that develops early in the course of illness and affects most patients who exhibit some degree of reduced renal function. Erythropoietin (EPO) deficiency is considered the most important cause of anemia in CKD. Renal anemia has serious clinical consequence. In addition to reducing patient physical capacity and quality of life, anemia induces adaptive cardiovascular mechanisms that increase the risk of cardiovascular disease and death. Thus, treatment of anemia in CKD is very important. While EPO is effective in correcting anemia in most cases, up to 10% of patients however, have an inadequate response to therapy. The two most common and important reasons why patients become relatively unresponsive to EPO therapy are the development of true iron deficiency and the onset of an inflammatory state that impairs the response to EPO. Indeed, the role of inflammation and pro-inflammatory cytokines in resistance to EPO therapy is gaining increasing recognition. On the other hand, the main organ for C-reactive protein (CRP) synthesis is the liver and it is well known that the synthesis of an acute-phase proteins by the liver is up regulated by inflammation. The main consequence of nonalcoholic fatty liver disease (NAFLD) is sub-chronic liver inflammation that leads and contributes to dyslipidemia, inflammation, enhanced oxidative stress and endothelial dysfunction. Considering the recent data about high prevalence of NAFLD in CKD patients, probably due to shared metabolic risk factors, we hypothesized that end-stage renal disease (ESRD) patients with NAFLD will need a much higher dose of EPO to achieve the target hemoglobin levels in comparison with ESRD patients without NAFLD. The possible underlying mechanism is sub-chronic liver inflammation in NAFLD patients that leads and contributes to poor response to EPO. Therefore, we believe that NAFLD could be a new clinical marker of poor response to EPO therapy in ESRD patients. Optimizing response to EPO therapy is important for both patient outcomes and the cost of treatment, and require consideration of a growing number of factors. Detection of NAFLD by some of non-invasive methods in ESRD patients could identify responsiveness and resistance to EPO therapy. Furthermore, we propose that all the patients who undergo dialysis treatment should be screened for NAFLD in order to identify the patients that will have a poor response to EPO therapy. The work could help to determine whether we have a new marker of poor EPO response in ESRD patients

Non-alcoholic fatty liver disease; a part of the metabolic syndrome in the renal transplant recipient and possible cause of an allograft dysfunction

Despite all improvements in transplant medicine, renal transplant recipients have a high risk for cardiovascular mortality. A high prevalence of cardiovascular complications in renal transplant recipients (RTR) is explained by cardiovascular risk factors present before transplantation, in addition to the development of new risk factors as well as worsening of preexisting risk factors after transplantation. A majority ot these patients develop metabolic syndrome within a year after the transplantation. The metabolic syndrome (MS) is associated with impaired renal allograft function and increased insulin resistance. Non alcoholic fatty liver disease (NAFLD) represents a liver manifestation of metabolic syndrome and it development is strongly associated with all components of MS in general population. The current importance of NAFLD and its link to the MS has encouraged an interest in its possible role in the development of atherosclerosis in recent years. Considering the fact that all components of MS are more common among renal transplant recipients compared to general population, it would be expected that RTR may have a much higher incidence of NAFLD compared to general population. We propose that the presence of NAFLD in RTR could be a strong predictor in cardiovascular morbidity and mortality. Also, according to the recent investigations about the possible link between NAFLD and chronic kidney disease, we hypothesis that NAFLD may be associated with deteriorating graft function, causing a chronic allograft nephropathy and graft loss. Common factors underlying the pathogenesis of NAFLD and chronic allograft dysfunction may be insulin resistance, oxidative stress, activation of rennin-angiotensin system, and inappropriate secretion of inflammatory cytokines by steatotic and inflamed liver. (C) 2013 Elsevier Ltd. All rights reserved

Mikolasevic)

a b s t r a c t Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Today it is believed that NAFLD is a hepatic manifestation of metabolic syndrome, and thus it is closely related to the cardiovascular morbidity and mortality. Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in patients with end-stage-renal disease (ESRD). NAFLD and ESRD share some important cardiometabolic risk factors and possible common pathophyisiological mechanisms, and are linked to an increased risk of incident CVD events. We hypothesize that the coexistence of these two conditions could lead to much faster progress of the aterogenic process. Furthermore, patients with ESRD who suffer from NAFLD have a much higher risk for the development of adverse CVD events. Given the high prevalence of NAFLD, and its tight association with other manifestations of the metabolic syndrome and thus cardiovascular complications, it is important to recognize and aggressively treat this condition in ESRD patients. To evaluate this hypothesis, we propose the use of non-invasive methods such as transient elastography (TE) (Fibroscan-CAP) for the detection and quantification of liver steatosis and fibrosis, as well as an abdominal ultrasound for detecting liver steatosis. We focus on their correlation with carotid intima-media thickness (IMT) and plaque as surrogate measures of increased cardiovascular risk in HD patients in order to investigate the association of NAFLD and increase risk of adverse CVD events. This evaluation will prove useful in assessing the risk in HD patients with NAFLD for increase CVD mortality. Ó 2013 Elsevier Ltd. All rights reserved. Introduction Chronic kidney disease (CKD) is a worldwide health problem and according to recent data from the United States populationbased third national health and nutrition examination survey (NHANES III) the prevalence of CKD in the United States is approximately 13% Recently non-alcoholic fatty liver disease (NAFLD) has been recognized as a new risk factor for development of atherosclerosis in the general population. The term NAFLD is used to cover a spectrum of diseases that are characterized predominantly by macrovesicular steatosis of the liver and occur in people who do not consume large amounts of alcohol. Today, there is growing evidence that NAFLD is strongly associated with cardiovascular diseases. Furthermore, many authors have expressed their opinion that NAFLD represents a liver manifestation of metabolic syndrome (MS)-disease which is related to diabetes mellitus type 2, insulin 0306-9877/$ -see front matter

Nonalcoholic fatty liver disease (NAFLD): A new risk factor for adverse cardiovascular events in dialysis patients

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Today it is believed that NAFLD is a hepatic manifestation of metabolic syndrome, and thus it is closely related to the cardiovascular morbidity and mortality. Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in patients with end-stage-renal disease (ESRD). NAFLD and ESRD share some important cardiometabolic risk factors and possible common pathophyisiological mechanisms, and are linked to an increased risk of incident CVD events. We hypothesize that the coexistence of these two conditions could lead to much faster progress of the aterogenic process. Furthermore, patients with ESRD who suffer from NAFLD have a much higher risk for the development of adverse CVD events. Given the high prevalence of NAFLD, and its tight association with other manifestations of the metabolic syndrome and thus cardiovascular complications, it is important to recognize and aggressively treat this condition in ESRD patients. To evaluate this hypothesis, we propose the use of non-invasive methods such as transient elastography (TE) (Fibroscan-CAP) for the detection and quantification of liver steatosis and fibrosis, as well as an abdominal ultrasound for detecting liver steatosis. We focus on their correlation with carotid intima-media thickness (IMT) and plaque as surrogate measures of increased cardiovascular risk in HD patients in order to investigate the association of NAFLD and increase risk of adverse CVD events. This evaluation will prove useful in assessing the risk in HD patients with NAFLD for increase CVD mortality

Nonalcoholic Fatty Liver Disease in Renal Transplant Recipients Proven by Transient Elastography

Background The increasing recognition of the importance of nonalcoholic fatty liver disease (NAFLD) and its strong association with the metabolic syndrome has stimulated interest in the putative role of NAFLD in the development and progression of cardiovascular disease. Furthermore, recent studies investigated the association of NAFLD and chronic kidney disease. We analyzed the incidence of NAFLD diagnosed by transient elastography (TE) in renal transplant recipients (RTRs). We also assessed whether TE-defined NAFLD is associated with decreased graft function in RTRs. Methods Our study included 73 RTRs with a functioning graft for more than 1 year. Liver stiffness was used to assess liver fibrosis and the controlled attenuation parameter (CAP) was used to detect and quantify liver steatosis by using TE (Fibroscan, Echosense, Paris, France). Therefore, with CAP being implemented on TE, both steatosis and fibrosis could be evaluated simultaneously. According to this evaluation, NAFLD was defined by the presence of steatosis with CAP values ≥238 dB.m −1 regardless of presence or absence of any stage of fibrosis. Results According to the TE findings, NAFLD was present in 57.5% of RTRs. We have found that the severity of liver steatosis was positively correlated with serum creatinine levels (r = 0.664; P < .0001) and negatively correlated with estimated glomerular filtration rate (eGFR; r = −0.692; P < .0001) levels. The severity of liver fibrosis was positively correlated with the serum creatinine, serum iron, and C-reactive protein levels indicating a more severe form of NAFLD in those patients. None of the investigated liver tests showed any differences between those RTR patients who had NAFLD compared to those without NAFLD. Conclusion Our results showed that RTRs have high prevalence of TE-defined NAFLD which possibly contributes to graft dysfunction. Measuring aminotransferase levels would not be a useful tool for NAFLD detection in RTRs. Our study showed the value of TE as an effective, noninvasive screening method for the diagnosis of NAFLD in RTRs

Nonalcoholic fatty liver disease (NAFLD) &ndash; a new factor that interplays between inflammation, malnutrition, and atherosclerosis in elderly hemodialysis patients

Ivana Mikolasevic,1 Vesna Lukenda,2 Sanjin Racki,1 Sandra Milic,3 Branka Sladoje-Martinovic,1 Lidija Orlic1 1Department of Nephrology, Dialysis and Transplantation, Rijeka University Hospital Center, Rijeka, Croatia; 2Department of Internal Medicine, Dr Josip Bencevic General Hospital, Slavonski Brod, Croatia; 3Department of Gastroenterology, Rijeka University Hospital Center, Rijeka, Croatia Background/aim: In the past decade, in most regions of the world, an increasing number of adults aged 65 years and older were started on renal replacement therapy each year. In contrast to the general population for whom overnutrition or obesity is associated with increased cardiovascular risk, for patients who are maintained on hemodialysis (HD), malnutrition and malnutrition-inflammation complex syndrome are associated with poor outcome. In recent years, nonalcoholic fatty liver disease (NAFLD) has been considered to be the liver manifestation of metabolic syndrome, and the development of NAFLD is strongly associated with all components of metabolic syndrome (arterial hypertension, dyslipidemia, obesity, and diabetes mellitus type 2) in the general population. The primary end point of this study was to determine the patient&rsquo;s survival in relation to nutritional and inflammatory state and the presence or absence of NAFLD. The secondary end point of this analysis was the association among NAFLD and various clinical and laboratory data, with the nutritional and inflammatory state of our elderly HD patients. Methods: Using a single-center, prospective, cohort study design, we followed the progress of 76 patients who were &ge;65 years and treated with chronic HD for at least 6 months, at the Department of Nephrology, Dialysis and Transplantation. All patients were followed for a minimum of 18 months or until death. Survival was defined as the time from study initiation to death (or end of study, if still alive).Results: The main findings of our study were a remarkable positive correlation between NAFLD and high-sensitivity C-reactive protein (hs-CRP) (r=0.659; P&lt;0.0001) and consequent negative correlation with the nutritional parameter, serum albumin (r=-0.321; P=0.004). Interestingly, we showed that in contrast to the general population, where NAFLD is associated with obesity, in the present study, there was no statistically significant association between NAFLD and overnutrition in elderly HD patients. Furthermore, the presence of NAFLD, low serum albumin levels, and high hs-CRP were strong predictors of poor outcome in our elderly HD patients. Conclusion: Our results indicated that NAFLD probably interplays between inflammation, malnutrition, and atherosclerosis in elderly HD patients. NAFLD could be a new factor that contributes to type 2 malnutrition in elderly HD patients, who may be amenable to adequate nutritional and HD support. Keywords: cardiovascular risk, serum albumin, high-sensitivity C-reactive protein (hs-CRP

Vitamin D for treatment of non-alcoholic fatty liver disease detected by transient elastography: A randomized, double-blind, placebo-controlled trial

Abstract Aim: To evaluate the effects of vitamin D on transient elastography (TE, FibroScan) indices of liver steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement [LSM]) in adults with non-alcoholic fatty liver disease (NAFLD). Patients and methods: In this randomized (2:1), double-blind, single-centre, 12-month trial, patients with NAFLD were treated with vitamin D (1000 IU/day) (n = 201) or a matching placebo (n = 110). Two co-primary outcomes were changes in CAP and LSM after 360 days of treatment versus baseline. Two main secondary outcomes were CAP/LSM changes after 180 days of treatment. Results: Both CAP and LSM gradually decreased in vitamin D-treated patients and slightly increased in the placebo arm. Vitamin D was superior to placebo for both primary outcomes (mean differences in CAP and LSM changes (-49.5 dB/m [95% CI -59.5 to -39.4] and -0.72 kPa [95% CI -1.43 to 0.00], respectively) and both secondary outcomes (-22.1 dB/m [-32.1 to -12.1] and -0.89 kPa [-1.61 to -0.17], respectively). Of a number of exploratory outcomes (change at 12 months vs. baseline), vitamin D reduced serum uric acid (-17.9 μmol/L [-30.6 to -5.2]), gamma-glutamyltransferase (-8.9 IU/L [-15.5 to -2.3)] and fasting serum insulin levels (-5.1 pmol/L [-9.3 to -0.8]) as well as the homeostatic model assessment of insulin resistance index (-1.6 [-3.1 to -0.2]) (false discovery rate [5%]-adjusted P-values between .0572 and .0952). Conclusion: Low-medium dose supplementation of vitamin D (1000 IU/day) over 12 months reduces TE indices of liver steatosis (CAP) and fibrosis (LSM) in NAFLD patients

Prospective evaluation of non-alcoholic fatty liver disease by elastographic methods of liver steatosis and fibrosis; controlled attenuation parameter and liver stiffness measurements

To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD)