Jasna Slaviček

Efficacy of Interferon-α in the Treatment of Chronic Hepatitis C in Dialysis Patients: Two Therapeutic Protocols Compared

Background: Data on the efficacy of particular therapeutic protocols of interferon-α (IFN-α) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary. Aim: To compare the efficacy of two different therapeutic protocols for HD patients. Patients and Methods: 15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-α 3 × 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-α 3 × 5 MU/week for 3 months, then 1 × 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection. Results: ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR [50% (4/8) vs. 28.5% (2/7)] and lower drop-out rate [0% (0/8) vs. 28.5% (2/7)] were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05). Conclusion: Therapy with IFN-α 3 × 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.

Cytokines and growth factors in mostly atherosclerotic patients on hemodialysis determined by biochip array technology.

Abstract Background: The lifespan of patients with chronic renal failure (CRF) is reduced, and coronary artery disease is the leading cause of morbidity and mortality in these patients. The progression of atherosclerosis is accelerated and angiogenesis is impaired in CRF. Risk factors that could contribute to further understanding of vascular pathology include markers of inflammation and growth factors. The purpose of this study was to determine the levels of cytokines (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, IL-1β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interferon-γ (IFNγ), tumor necrosis factor-α (TNFα) and monocyte chemotactic protein-1 (MCP-1) in patients on chronic hemodialysis (HD; n=75), and to compare values with those of control subjects (n=113). Methods: Evidence® biochip array analyzer was used for quantification of plasma concentrations in samples. Results: Significant differences were found between the control subjects and HD patients. IL-2 (p<0.001), IL-4 (p<0.001) and EGF (p<0.001) levels were higher in controls than in HD patients, while IL-6 (p<0.001), IL-8 (p=0.081), IL-10 (p=0.008), TNFα (p<0.001), IL-1β (p<0.001) and MCP-1 (p<0.001) levels were higher in HD patients. We also found IL-2 (p=0.015) and IL-1α (p=0.035) levels to be significantly higher in males than females, while IL-4 (p=0.025) and IL-1β (p=0.049) levels were significantly higher in females. Among HD patients, IL-2 levels were higher in patients under the age of 50 years (p<0.048). It was also higher in female than in male patients (p<0.035) and in patients on HD for more than 10 years (p<0.009). IL-6 levels were higher in patients over the age of 50 years (p<0.047). Patients with previous glomerulonephritis had the highest level of IL-6 compared to patients with previous pyelonephritis and diabetes mellitus (p<0.063). IL-6 levels were higher in patients with concomitant hepatitis C virus (HCV) infection (p<0.036) and in patients with developed atherosclerosis (p<0.003). IL-8 levels were higher in patients over the age of 50 years (p<0.003) and in the group with previous glomerulonephritis (p<0.031). IL-10 levels were higher in the group with developed atherosclerosis (p<0.045). EGF was the highest in the group of patients with previous diabetes mellitus compared to pyelonephritis and glomerulonephritis groups (p<0.073). TNFα levels were higher in the patient population on HD for more than 10 years (p<0.032) and in the concomitant HCV group (p<0.073). IL-1β levels were higher in the HCV group (p<0.088). Conclusions: Plasma concentrations of some cytokines and growth factors could serve as useful diagnostic and prognostic parameters for patients with CRF on HD. Clin Chem Lab Med 2007;45:1347–52.

Pegylated interferon for treatment of chronic hepatitis C in hemodialysis patients in Croatia

Background and Aims: Hepatitis C virus (HCV) infection is a frequent complication among long-term dialysis patients. The aim of the present study was to evaluate the efficacy and side effects of pegylated interferon-α2a (PEG-IFN-α2a) treatment in hemodialysis patients. Methods: We retrospectively reviewed charts of 16 HCV-RNA-positive hemodialysis patients. Results: There were 11 male and 5 female patients treated with dialysis for 6–28 years. Twelve patients had HCV genotype 1b, 2 patients had 3a, and 1 patient had genotype 2a. Although only 10 out of 16 patients completed 48 weeks of treatment, early virological response and end-of-treatment virological response were achieved in 9 and 13 patients, respectively. Sustained virological response was recorded in 9 patients. The most common side effect was anemia. A flu-like syndrome was documented in 6, myalgia in 4, and arthralgia in 5 patients. Rectorrhagia, endocarditis and severe cough were recorded in 1 patient each. Nine patients received a renal transplant, and all 6 responders remained HCV-RNA-negative. Conclusions: PEG-IFN-α2a has limited efficacy in dialysis patients. A significant proportion of patients discontinued treatment because of side effects. Additional studies with long-term follow-up are needed to determine the optimal treatment of HCV infection in the dialysis population.

High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: Success or waste of organs? the Eurotransplant 15-year all-centre survey

BACKGROUND In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

Bone density in renal transplant recipients and in patients with chronic kidney disease: a follow-up study in children and adolescents.

AIMS Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease. The purpose of this follow-up study was to compare the change of bone mineral density in patients with chronic kidney disease to those who have received the renal transplant. METHODS The study included 47 children and adolescents: 16 with mild to moderate kidney disease, 14 on dialysis and 17 patients with renal transplant. At the baseline and follow-up visits, regular biochemistry, anthropometry and bone mineral density were measured. To minimize the effect of skeletal size, bone mineral apparent density (BMAD; g/cm3) was calculated. RESULTS The mean height was below one standard deviation from reference values in patients on dialysis and in those with renal transplant. After correction for age, baseline and follow-up BMAD did not differ significantly between patients after transplantation and those with chronic kidney disease. The increase of BMAD between two measurements (mean period 16.0 +/- 4.4 months) was not significantly higher in patients with kidney transplant compared to those with chronic kidney disease. The significant predictors of BMAD were PTH in patients with chronic kidney disease and duration of steroid therapy in patients with renal transplant. CONCLUSIONS The results showed that bone density in children and adolescents, even several years after kidney transplantation, did not significantly change over time comparing to patients with chronic kidney disease. Hyperparathyroidism and steroid therapy were the most important risk factors for the slow increase of bone density.

The role of noninherited HLA haplotypes in inducing donor-specific hyporesponsiveness

The ultimate goal of clinical transplantation is the induction of donor-specific unresponsiveness to MHC antigens without the impairment of host defense mechanisms. One possible route to a tolerance assay my be through a better understanding of mechanisms involved. Recent study have suggested that exposure of the fetus and newborn to noninherited maternal HLA antigens has a life-long effect on allograft recognition that could influence tolerance of organ grafts.