SUMMARYBackground: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. Aim: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. Methods: We screened a large cohort (n ¼ 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n ¼ 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. Results: Occult hepatitis B virus infection was absent (zero of 213 ¼ 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P ¼ 0.0001]. No dialysis

Dialysis patients remain a high-risk group for hepatitis C virus (HCV) infection. The current diagnosis of HCV infection among dialysis patients includes serological assays and nucleic acid amplification technology (NAT) for assessing serum anti-HCV antibody and HCV viremia, respectively. However, current NAT techniques are expensive and labor-intensive and often lack standardization. An assay prototype designed to detect and quantify total HCV core antigen (total HCV core Ag) protein in serum and plasma in the presence or absence of anti-HCV antibodies has been recently developed. A comparison between a total anti-HCV core Ag enzyme-linked immunosorbent assay (ELISA) and a quantitative HCV RNA assay based on reverse transcription-PCR (RT-PCR) (Amplicor HCV Monitor test) was performed using a large (n ‫؍‬ 305) cohort of ELISA HCV 3.0 HCV-negative and -positive patients on maintenance dialysis. The concentrations of HCV core Ag and HCV RNA levels (measured by RT-PCR) were significantly correlated (r ‫؍‬ 0.471, P ‫؍‬ 0.0001) over a wide range of HCV RNA levels and were maintained among different HCV genotypes (HCV genotype 1, r ‫؍‬ 0.862, P ‫؍‬ 0.0001; HCV genotype 2, r ‫؍‬ 0.691, P ‫؍‬ 0.0001). We estimated that 1 pg of total HCV core Ag per ml is equivalent to approximately 19.952 IU of HCV RNA per ml, even if the wide range in the ratio of core Ag to HCV RNA (95% confidence intervals, 2.8 ؋ 10 3 to 1.6 ؋ 10 5 IU/ml) precluded definitive conclusions. In summary, total HCV core Ag proved to be useful for performing HCV RNA measurement among dialysis patients in routine laboratories without the need for special equipment or training. The present study supports the use of the total anti-HCV core Ag ELISA for assessing viral load among dialysis patients with HCV infection.Dialysis patients remain a high-risk group for hepatitis C virus (HCV) infection (11). The Centers for Disease Control and Prevention, Atlanta, Ga., have recently included semiannual anti-HCV testing for anti-HCV-negative patients in their infection control practices for hemodialysis units (6, 7).Routine diagnosis of HCV is based on detection of anti-HCV antibody. However, due to the absence of an efficient in vitro culture system for HCV or assays capable of detecting viral antigens, direct detection of HCV has depended on nucleic acid amplification technology (NAT) techniques. Indeed, serological assays for detecting anti-HCV antibody cannot distinguish between patients with active infection and those who have cleared the virus (29). NAT tests are based on nucleic acid amplification (PCR and transcription-mediated amplification) (16, 37) or signal amplification (branched-chain DNA assay) and are currently used to detect viremia (2, 36). Recently both assay systems have become semiautomated. Several problems still persist with these methods; PCR requires considerable skill and has limited reproducibility, while the branched-chain DNA assay requires a long incubation period. Both assays are also expensive. An assay prototype designed to detect and ...

No abstract

Background The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been one of the major advances in the management of patients with end-stage renal disease (ESRD). However, clinical and biochemical expression of HBV in dialysis patients have not been adequately addressed. Elevated values of serum aminotransferase activity are a sensitive measure of hepatocellular injury, but the role of HBV infection in the development of liver disease among dialysis patients has not been adequately analysed. Also, the clinical impact related to the virological characteristics of HBV in dialysis has not been evaluated. Methods Demographic, biochemical and virological data from 727 patients undergoing chronic dialysis in seven dialysis units in northern Italy were collected in order to assess the biochemical consequences related to the presence of HBV infection in this population. We have measured by RT-PCR technology the titers of HBV viremia in HBsAg positive patients receiving dialysis. Results Univariate analysis showed that AST and ALT values were significantly higher in HBsAg positive/HBV DNA positive than HBsAg negative patients on dialysis; AST, 22.86±31.34 vs. 14.19±9.7 IU/L (P=0.00001); and ALT, 25.07±41.59 vs. 13.9±41.59 IU/L (P=0.00001). In the subgroup of HBsAg positive patients, the frequency of detectable HBeAg in serum was 14.9% (7/47). The median value of HBV DNA in patients with detectable HBV DNA in serum was 2.160 × 103 copies/mL (range, 2.5 × 102 - 4 × 106 copies/mL). HBsAg positive/HCV positive patients had higher aminotransferase activity than other subgroups (P=0.0001). Multivariate analysis showed a significant and independent association between detectable HBsAg/HBV DNA in serum and AST (P=0.00001) and ALT (P=0.0001) activity. AST and ALT levels were lower in dialysis than healthy individuals – this finding persisted in age- and gender-matched comparisons. Conclusions The HBV viral load in HBsAg positive patients receiving maintenance dialysis is not high. HBsAg positivity with detectable HBV DNA in serum is a strong and independent predictor of raised aminotransferase activity among dialysis patients. HBsAg positive patients had greater aminotransferase activity than HBsAg negative individuals even if both the groups had mean aminotransferase levels within the normal range considered for healthy population. Clinical trials aimed at identifying the best cut-off value to enhance the diagnostic yield of AST/ALT for detecting HBV in dialysis population are under way.

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.