Our data show that detectable HCV RNA in serum is a strong independent predictor of raised aminotransferase values in chronic dialysis patients; the relationship between serum aminotransferase values and anti-HCV antibody was exclusively related to the association between raised aminotransferase values and HCV viraemia; HCV RNA positive patients show higher hepatic enzyme levels than dialysis patients with no detectable HCV RNA; no association between HCV genotype and serum aminotransferase activity was apparent.
The aim of the present study was transmembrane pressure (TMP) modulation in high-volume mixed hemodiafiltration (HDF) to optimize efficiency and minimize protein loss. The optimal flow/pressure conditions in on-line mixed HDF assisted with a feedback control of TMP were defined in this prospective randomized study in order to obtain maximal efficiency in solute removal while minimizing potential side effects. Two different TMP profiles in mixed HDF were compared in 12 unselected patients who underwent two study periods of 2 weeks each in cross-over randomized sequence: (A) constant TMP at around 300 mmHg and (B) profiled TMP, in which TMP was slowly increased from a low initial value to the maximal value. In both procedures, the mean volume exchange was 10.6+/-1.4 l/h. Mean filtration fraction was 53%. Instantaneous beta2-microglobulin (beta2-m) clearance was higher at the start of the session with profiled TMP (207+/-35 vs 194+/-28 ml/min, P<0.005), whereas no differences were found at the end (135+/-19 vs 132+/-19 ml/min). Profiled TMP resulted in a higher mean beta2-m clearance of the session (97.0+/-15.4 vs 87.8+/-18.3 ml/min, P<0.01), in lower albumin loss in the first 30 min (0.62+/-0.14 vs 0.98+/-0.18 g, P<0.0001), and, in the whole session (3.98+/-1.19 vs 5.24+/-0.77 g, P<0.001), in higher dialyzer ultrafiltration coefficients and lower resistance indexes. This study showed that the TMP feedback modulation in mixed HDF was highly effective in maintaining very high ultrafiltration rates and filtration fractions, and minimized potential side effects as a result of the improved preservation of membrane permeability and more favorable dialyzer pressure regimen.
The efficacy of monotherapy with interferon (IFN) (conventional or pegylated IFN) in dialysis patients with chronic hepatitis C remains unclear, although a number of clinical trials have been published addressing this issue. The aim of the study was to evaluate the efficacy and safety of monotherapy by conventional or pegylated IFN in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (SVR; as a measure of efficacy), and the secondary outcome was drop-out rate (as a measure of tolerability). We used the random-effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 28 clinical trials (645 unique patients), of which six (21.4%) had a controlled design. In the group of trials based on conventional IFN, the summary estimate for SVR and drop-out rate was 39% [95% confidence interval (CI) 32-46] and 19% (95% CI 13-26) respectively. The summary estimate for SVR rate in patients with the hepatitis C virus genotype 1 was 33% (95% CI 19-47). In the subset of trials using pegylated IFN, the summary estimate for SVR and drop-out rate was 31% (95% CI 7-55) and 27% (95% CI 1-52) respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms, and gastrointestinal and haematological changes. A relationship between age and drop-out rate was found, even if no statistical significance was reached (P = 0.064). The studies were heterogeneous with regard to SVR and drop-out rate. No publication bias was observed. One-third of dialysis patients with chronic hepatitis C were successfully treated with conventional or pegylated IFN monotherapy. Preliminary evidence does not support additional benefit due to monotherapy with pegylated IFN on the viral response in the chronic kidney disease (CKD) population. Tolerance to IFN monotherapy was unsatisfactory, particularly to pegylated IFN. The optimal antiviral treatment of chronic hepatitis C in dialysis populations is currently under active investigation.
There are very few data on the molecular biology of hepatitis C virus (HCV) infection in dialysis patients. 101 patients undergoing dialysis treatment in 4 units in the Lombardy, northern Italy, were analyzed by RT-PCR for HCV viremia, by line probe assay technology for HCV genotyping and by a serological analysis for detecting type-specific antibodies. 61 of 101 (60%) patients showed detectable HCV RNA in serum; HCV genotype 2a was dominant (30/ 53 = 57%), followed by HCV genotype lb (20/53 = 37%). There was no relationship between HCV genotyping and the clinical or demographic features of the patients. The antibody response toward the c33-c, cl00-3, and 5-1-1 antigens was more frequent in HCV genotype lb compared with genotype 2a (p = 0.046, p = 0.001 and p = 0.0001, respectively). The antibody levels to NS-3 and NS-4 HCV proteins were significantly higher in patients with HCV genotype lb in comparison with HCV 2a-infected individuals (p = 0.0001). There was a high level (82%) of agreement between HCV genotyping by RT-PCR and the assessment of type-specific antibodies by serological analysis; further, it was possible to detect type-specific antibodies in 6 of 22 (27%) patients in whom PCR amplification was unsuccessful. In conclusion, HCV subtype 2a was dominant in our population of HCV-infected dialysis patients, dialysis patients infected by different genotypes showed similar demographic and clinical characteristics, the antibody response toward the NS-3- and NS-4-related antigen of HCV was genotype dependent. There was a high level of agreement between HCV genotyping by RT-PCR and the detection of type-specific antibodies by serological analysis. As significant biological differences may exist among HCV strains, the assessment of HCV types may be very useful in the routine clinical activity of nephrologists in dialysis units.
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