Gabriele Donati

Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance

Background: The conditions associated with fatty liver disease presenting with normal liver enzymes and the mechanism involved in its development remain to be fully elucidated. Aims: The aim of the present study was to test the hypothesis that fatty liver with normal liver enzymes occurs more frequently in arterial hypertensive patients and to establish whether this condition is associated with insulin resistance. Patients: A total of 55 non-obese, non-diabetic, non-heavy alcohol drinking patients with arterial hypertensive and normal liver enzymes and 55 sex and age matched healthy subjects were enrolled into the study. Methods: Plasma metabolic parameters, body mass index, and the presence of fatty liver were investigated. Insulin resistance was estimated from plasma insulin and glucose as the homeostasis model assessment index. Stepwise logistic regression and multivariate regression analysis were used on the combined sample to identify variables independently associated with fatty liver and insulin resistance. Results: Hypertensive patients had a significantly higher prevalence of fatty liver (30.9% v 12.7%; p<0.041), higher insulin resistance (mean 2.27 (SD 1.81) v 1.56 (0.70); p = 0.022), and slightly higher body mass index (24.9 (3.0) v 24.0 (2.2); p = 0.043) than controls. Multivariate logistic regression identified insulin resistance (odds ratio 1.66 (95% confidence interval (CI) 1.03–2.52)) and body mass index (OR 1.22 (95% CI 1.00–1.49)) as factors independently associated with fatty liver. Multivariate regression analysis showed insulin resistance to be predicted by alanine transaminase (p = 0.002), presence of arterial hypertension (p = 0.029), and body mass index (p = 0.048). Conclusion: The higher prevalence of non-alcoholic fatty liver in non-obese hypertensive patients with normal liver enzymes appears to be related to increases in insulin resistance and body weight.

Diffusion MRI shows increased water apparent diffusion coefficient in the brains of cirrhotics

Background: Brain edema and increased intracranial pressure worsen prognosis in patients with end-stage chronic cirrhosis. Objective: To use diffusion-weighted imaging (DWI) to quantify water apparent diffusion coefficient (ADC) in different brain regions of patients with chronic liver failure with or without hepatic encephalopathy. Methods: The authors studied 14 patients with viral liver cirrhosis and 12 sex- and age-matched healthy volunteers. Seven patients had no clinical evidence of hepatic encephalopathy; six had grade I hepatic encephalopathy; and one had grade II hepatic encephalopathy. Brain DWI was obtained using a single-shot echo-planar imaging sequence, and four gradient strengths (b values = 0, 300, 600, and 900 s/mm2) were applied to calculate the average diffusivity maps. Results: Mean ADC values in the brains of patients with cirrhosis were significantly increased in all selected regions of interest (caudate, putamen, and pallidus nuclei; occipital, parietal, and frontal lobe white matter) except in the thalamus. Venous ammonia was linearly related to ADC values in deep gray and white matter regions of interest. Conclusions: Brain water apparent diffusion coefficient is increased in patients with chronic liver disease and may be useful in monitoring patients with hepatic encephalopathy.

Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension.

The accuracy of various Doppler parameters of portal circulation in the diagnosis of relevant portal hypertension (presence of gastroesophageal varices) was prospectively validated. The following parameters were compared in 51 patients with chronic liver disease (40 with cirrhosis and 11 with chronic hepatitis): portal vein flow velocity and congestion index, hepatic and splenic arteries resistance indexes (RI), modified liver vascular index (portal flow velocity/hepatic artery RI) and portal hypertension index, a new index calculated as: [(hepatic artery RI x 0.69) x (splenic artery RI x 0.87)]/portal vein flow velocity. Highest accuracy was achieved by the splenic artery RI and the portal hypertension index (both around 75%) at cut-offs, respectively, of 0.60 and 12 cm/s(-1), which appeared to be, therefore, the most favorable parameters for the clinical practice. Their use may limit the need for endoscopy to search for varices.

Standard heparin versus low-molecular-weight heparin. A medium-term comparison in hemodialysis.

Background: To compare standard heparin (SH) and low molecular weight heparin (LMWH) in terms of anticoagulation, platelet activation and lipid metabolism, we selected 54 patients who had been on 4-hour hemodialysis three times weekly for at least 12 months, without bleeding disorders or dyslipidemic diseases. 28 were on hemodialysis with Polysulfone low-flux, 26 were on hemodiafiltration with Polysulfone high-flux. All patients underwent EPO. Methods: During the first 18 months, we administered SH 1,500 IU on starting dialysis and 1,500 ± 500 IU in continuous intradialytic infusion per session. In the following 18 months, we administered LMWH 64.6 IU/kg on starting dialysis in a single arterious bolus. We assessed aPTT, anti-factor Xa activity, TAT and FPA, β-TG and PF4. Blood samples were taken monthly at times 0, 30, 60, 180 and 240 min, as well as 1, 4 and 20 h after dialysis end. Predialysis cholesterol, HDL, LDL, triglycerides and lipoprotein(a) were checked monthly. Results: During both LMWH and SH sessions no clotting or major bleeding complications were observed. APTT with LMWH was lower than that found with SH (p < 0.001); aFXa using LMWH was higher than when using SH (p < 0.001); TAT and FPA were lower in LMWH sessions (p < 0.01) than in SH sessions. We also detected lower β-TG (p < 0.05) and PF4 levels (p < 0.05) using LMWH than using SH. As regards lipids, we only observed a significant decrease in triglycerides after 18 months of LMWH treatment. Conclusions: Routine use of LMWH during hemodialysis affords a safe and effective alternative to SH, and causes reduced platelet activation.

5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

BACKGROUND Hemodialysis (HD) patients have a greatly increased risk of cardiovascular morbidity and mortality. For this reason, attempts are often made to normalize hyperhomocysteinemia. This randomized prospective study sought to determine which risk factors are predictors of mortality and whether high doses of folates or 5-methyltetrahydrofolate (5-MTHF) could improve hyperhomocysteinemia and survival in HD patients. METHODS 341 patients were divided into two groups: group A was treated with 50 mg i.v. 5-MTHF, and group B was treated with 5 mg/day oral folic acid. Both groups received i.v. vitamin B(6) and B(12). By dividing patients into C-reactive protein (CRP) quartiles, group A had the highest survival for CRP <12 mg/l, whereas no survival difference was found for group B. CRP was the only predictive risk factor for death (RR 1.17, range 1.04-1.30, p = 0.02). Dialysis age, hyperhomocysteinemia, methylenetetrahydrofolate reductase polymorphism, albumin, lipoprotein (a) and folate did not influence mortality risk. Survival in group A was higher than that in group B, namely 36.2 +/- 20.9 vs. 26.1 +/- 22.2 months (p = 0.003). RESULTS Our results suggest that CRP, but not hyperhomocysteinemia, is the main risk factor for mortality in HD patients receiving vitamin supplements. Intravenous 5-MTHF seems to improve survival in HD patients independent from homocysteine lowering.

Influence of liver fibrosis on hepatic artery Doppler resistance index in chronic hepatitis of viral origin

BACKGROUND Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. METHODS Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. RESULTS Hepatic artery resistance index and age were higher in patients with more severe liver fibrosis (respectively 0.638 +/- 0.084 and 39.0 +/- 10.9 (years) in mild fibrosis versus 0.687 +/- 0.060 and 49.4 +/- 14.4 (years) in severe fibrosis; P < 0.05 for both), whereas no difference between the two groups was found for the other histological features (degeneration, inflammation and necrosis), nor for portal flow velocity. CONCLUSIONS The increase in hepatic artery resistance index appears to be influenced by the extent of fibrous tissue deposition in the liver, determined by chronic inflammation and repair and, secondly, by ageing.Background: Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. Methods: Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. Results:

Coronary Calcifications in End-Stage Renal Disease Patients: A New Link between Osteoprotegerin, Diabetes and Body Mass Index?

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 ± 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca × P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-β1 (TGF-β1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0–7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-β1, OPG and days with Ca × P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.

MARS and Prometheus: Our Clinical Experience in Acute Chronic Liver Failure

INTRODUCTION In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

Hepatorenal syndrome: Update on diagnosis and treatment

Acute kidney injury (AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome (HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.

VDR Expression on Circulating Endothelial Progenitor Cells in Dialysis Patients Is Modulated by 25(OH)D Serum Levels and Calcitriol Therapy

Background/Aims: Vitamin D deficiency is associated with endothelial dysfunction in uremic patients, possibly by the impairment in the number and function of endothelial progenitor cells (EPCs). In 89 hemodialysis patients, we investigated the factors associated with the number of circulating EPCs (CD34⁺/CD133⁺/KDR⁺ and CD34⁺/CD133^–/KDR⁺ cells), the presence of VDR and the determinants of VDR expression on EPCs, in particular in calcitriol therapy. Methods: EPC counts, percentages of VDR-positive EPCs and VDR expression were assessed by flow cytometry. Cells isolated from a subgroup of patients were cultured to analyze colony-forming units, specific markers expression and a capillary-like structure formation. Results/Conclusions: Our study demonstrates the presence of VDR on EPCs. In our dialysis patients, the parameters studied on both CD34⁺/CD133⁺/KDR⁺ and CD34⁺/CD133^–/KDR⁺ cells, in particular VDR expression, seem to be influenced by uremia-related factors, including anemia, inflammation, diabetes, 25(OH)D serum levels and calcitriol therapy.