Clinical Practice: Original Paper Nephron 2015;129:202–208 DOI: 10.1159/000371450
Received: October 7, 2014 Accepted after revision: December 9, 2014 Published online: March 4, 2015
Hepatitis B and C Virus Infection in the Hemodialysis Population from Three Romanian Regions Adalbert Schiller a Romulus Timar b Dimitrie Siriopol d Bogdan Timar c Flaviu Bob a Oana Schiller f Vasile Drug e Adelina Mihaescu a Adrian Covic d Departments of a Nephrology, b Nutrition and Metabolic Diseases and c Functional Sciences, ‘Victor Babes’ University of Medicine and Pharmacy, Timisoara, Departments of d Nephrology and e Gastroenterology, ‘Gr. T. Popa’ University of Medicine and Pharmacy, Iasi, and f ‘Avitum’ Dialysis Center, Timisoara, Romania
Abstract Background: After 10 years of systematically nationwide applied measures for reduction of infection risk, in this national prospective observational study, we reassessed the prevalence of hepatitis virus infection prevalence and its influence on the outcome of end-stage kidney disease (ESKD) patients treated with hemodialysis. Methods: Six-hundred ESKD patients (332 men and 268 women, median age 56 years) treated with chronic HD in seven centers from all the historical regions of Romania have been assigned to this study on 1st of November 2010. The aims of this study were to reevaluate the prevalence of the hepatitis B and C virus infection in a HD population from Romania after 10 years of systematically nationwide applied measures for reduction of infection risk and also to assess the impact of these infections on the prognosis of HD patients. Results: HBsAg was positive in 9.5% (n = 57) of the patients, anti-HCV antibodies were detected in 27.3% (n = 164) and 5% (n = 30) were positive for both HBV and HCV infection. The mortality risk was significantly influenced only by age, the presence of coronary artery disease and the 25 OH vitamin D levels. Conclusions: This study
© 2015 S. Karger AG, Basel 1660–8151/15/1293–0202$39.50/0 E-Mail [email protected] www.karger.com/nef
shows that the systematically nationwide applied measures for reduction of infection risk significantly decreased HV infection prevalence in HD patients in Romania. The presence of HV infection did not significantly influence the mortality risk in this population. © 2015 S. Karger AG, Basel
Introduction
Hepatitis virus (HV) infections are the most common cause of chronic liver disease in the world. Patients with end-stage kidney disease (ESKD), and those hemodialyzed (HD) in particular, have a higher prevalence of hepatitis virus infections, ranging from 2 to 25% for C virus (HCV) [1] and from 0 to 22% for B virus (HBV) infection [2]. In 1999 in Romania, 2648 ESKD patients were treated by HD in 63 public centers [3]. During 1999 and 2000, two epidemiological studies reported on the HBV and HCV infection prevalence in HD populations, from two historical regions of Romania (Moldavia and Transylvania) [4, 5]. In Moldavia (Eastern Romania), HBV infection was detected in 17% and HCV in 75% of the HDtreated patients [4], while in Transylvania (Central and Western part of Romania), HBV infection was identified Prof. Adrian Covic Department of Nephrology ‘Gr. T. Popa’ University of Medicine and Pharmacy RO–6600 Iasi (Romania) E-Mail accovic @ gmail.com
Downloaded by: University of Birmingham 149.126.76.1 - 1/27/2016 8:33:05 AM
Key Words Hepatitis B infection · Hepatitis C infection · Hemodialysis · End-stage kidney disease · Mortality
Subjects and Methods Patients and Study Design 600 ESKD patients (332 men and 268 women) treated with chronic HD in seven HD centers from all the historical regions of Romania (Moldavia 184 patients, Muntenia 121 patients, Transylvania 295 patients) have been assigned to this prospective observational study on 1st of November 2010. At inclusion, patient’s data have been retrieved from their medical records: personal data (age, gender), anthropometric data (height, weight, BMI), medical history (etiology of CKD, coronary artery disease – CAD, peripheral vascular disease – PVD, stroke, diabetes mellitus – DM, blood and blood product transfusion), dialysis-related data (duration of dialysis therapy, previous 6 months average eKt/V, duration and number of dialysis sessions/week, type of dialyzer, Qb). The initial laboratory work-up included hemoglobin, ferritin, transferrin saturation, albumin, calcium, phosphorus, serum bicarbonate, intact parathyroid hormone (iPTH), 25-OH vitamin D, alanine aminotransferase (ALT), aspartate aminotransferase (AST). HBV and HCV infection status was detected by CmIA (Abbot) using Architect CI 8200 analyzers. HBV vaccination of HD staff and patients was performed according to the guidelines. All patients have been followed-up for 2 years or until death. Patients were censored if they were transplanted, switched to peritoneal dialysis or transferred to another dialysis unit. All patients were treated with high-flux, high-surface, polysulfone filters (not
Hepatitis Virus Infection in a HD Population from Romania
reused) and ready-to-use dialysis fluid (B. Braun acidic bicarbonate hemodialysis concentrate). HD therapy was performed on permanent tunneled catheters in 10.8% of the patients and using an arteriovenous fistula for the rest of the patients. Catheter-handling protocols are currently applied in all centers. Standard heparin (multi-dose ampoules) was used in 64.1% of the patients and LMWH in the rest. Surface sterilization after each HD session was applied routinely as per protocol. Patients in whom the hepatitis virus was positive were treated in isolated rooms and with separated dialysis machines for B, C and B+C infected patients. All HD staff members were negative for HBV and HCV markers. Statistical Analysis Data were collected and analyzed using the SPSS v.15 software suite (SPSS Inc., Chicago, Ill., USA). Data are presented as mean ± standard deviations for continuous variables with Gaussian distribution, median (interquartile range) for continuous variables without Gaussian distribution or percentages for categorical variables. The lower and upper limits of the 95% confidence intervals (CI), used to estimate the prevalence, were calculated according to Wilson’s procedure for variables with Poisson distribution. Moreover, the 95% CI for odds ratio (OR) was calculated according to the mid-p method for binomial distributions. To assess the significance of the differences between groups, the Student t-test (means, Gaussian populations), Mann-Whitney-U test (medians, non-Gaussian populations), Chi-square for trend (proportions) and log-rank test (differences between survival curves and hazard ratio) were used. Continuous variable distributions were tested for normality using the Shapiro-Wilk test, and for equality of variances using Levene’s test. Correlations and regression strength were evaluated using Pearson’s correlation coefficient, and its statistical significance was assessed using t-distribution’s test. For evaluating the involvement of more confounding factors in the survival prognosis, Cox proportional hazard regression models using the backward stepwise method and a removal probability of 0.05 were built. We included in the model all univariate predictors for mortality and the HV infection status. A p value of
Received: October 7, 2014 Accepted after revision: December 9, 2014 Published online: March 4, 2015
Hepatitis B and C Virus Infection in the Hemodialysis Population from Three Romanian Regions Adalbert Schiller a Romulus Timar b Dimitrie Siriopol d Bogdan Timar c Flaviu Bob a Oana Schiller f Vasile Drug e Adelina Mihaescu a Adrian Covic d Departments of a Nephrology, b Nutrition and Metabolic Diseases and c Functional Sciences, ‘Victor Babes’ University of Medicine and Pharmacy, Timisoara, Departments of d Nephrology and e Gastroenterology, ‘Gr. T. Popa’ University of Medicine and Pharmacy, Iasi, and f ‘Avitum’ Dialysis Center, Timisoara, Romania
Abstract Background: After 10 years of systematically nationwide applied measures for reduction of infection risk, in this national prospective observational study, we reassessed the prevalence of hepatitis virus infection prevalence and its influence on the outcome of end-stage kidney disease (ESKD) patients treated with hemodialysis. Methods: Six-hundred ESKD patients (332 men and 268 women, median age 56 years) treated with chronic HD in seven centers from all the historical regions of Romania have been assigned to this study on 1st of November 2010. The aims of this study were to reevaluate the prevalence of the hepatitis B and C virus infection in a HD population from Romania after 10 years of systematically nationwide applied measures for reduction of infection risk and also to assess the impact of these infections on the prognosis of HD patients. Results: HBsAg was positive in 9.5% (n = 57) of the patients, anti-HCV antibodies were detected in 27.3% (n = 164) and 5% (n = 30) were positive for both HBV and HCV infection. The mortality risk was significantly influenced only by age, the presence of coronary artery disease and the 25 OH vitamin D levels. Conclusions: This study
© 2015 S. Karger AG, Basel 1660–8151/15/1293–0202$39.50/0 E-Mail [email protected] www.karger.com/nef
shows that the systematically nationwide applied measures for reduction of infection risk significantly decreased HV infection prevalence in HD patients in Romania. The presence of HV infection did not significantly influence the mortality risk in this population. © 2015 S. Karger AG, Basel
Introduction
Hepatitis virus (HV) infections are the most common cause of chronic liver disease in the world. Patients with end-stage kidney disease (ESKD), and those hemodialyzed (HD) in particular, have a higher prevalence of hepatitis virus infections, ranging from 2 to 25% for C virus (HCV) [1] and from 0 to 22% for B virus (HBV) infection [2]. In 1999 in Romania, 2648 ESKD patients were treated by HD in 63 public centers [3]. During 1999 and 2000, two epidemiological studies reported on the HBV and HCV infection prevalence in HD populations, from two historical regions of Romania (Moldavia and Transylvania) [4, 5]. In Moldavia (Eastern Romania), HBV infection was detected in 17% and HCV in 75% of the HDtreated patients [4], while in Transylvania (Central and Western part of Romania), HBV infection was identified Prof. Adrian Covic Department of Nephrology ‘Gr. T. Popa’ University of Medicine and Pharmacy RO–6600 Iasi (Romania) E-Mail accovic @ gmail.com
Downloaded by: University of Birmingham 149.126.76.1 - 1/27/2016 8:33:05 AM
Key Words Hepatitis B infection · Hepatitis C infection · Hemodialysis · End-stage kidney disease · Mortality
Subjects and Methods Patients and Study Design 600 ESKD patients (332 men and 268 women) treated with chronic HD in seven HD centers from all the historical regions of Romania (Moldavia 184 patients, Muntenia 121 patients, Transylvania 295 patients) have been assigned to this prospective observational study on 1st of November 2010. At inclusion, patient’s data have been retrieved from their medical records: personal data (age, gender), anthropometric data (height, weight, BMI), medical history (etiology of CKD, coronary artery disease – CAD, peripheral vascular disease – PVD, stroke, diabetes mellitus – DM, blood and blood product transfusion), dialysis-related data (duration of dialysis therapy, previous 6 months average eKt/V, duration and number of dialysis sessions/week, type of dialyzer, Qb). The initial laboratory work-up included hemoglobin, ferritin, transferrin saturation, albumin, calcium, phosphorus, serum bicarbonate, intact parathyroid hormone (iPTH), 25-OH vitamin D, alanine aminotransferase (ALT), aspartate aminotransferase (AST). HBV and HCV infection status was detected by CmIA (Abbot) using Architect CI 8200 analyzers. HBV vaccination of HD staff and patients was performed according to the guidelines. All patients have been followed-up for 2 years or until death. Patients were censored if they were transplanted, switched to peritoneal dialysis or transferred to another dialysis unit. All patients were treated with high-flux, high-surface, polysulfone filters (not
Hepatitis Virus Infection in a HD Population from Romania
reused) and ready-to-use dialysis fluid (B. Braun acidic bicarbonate hemodialysis concentrate). HD therapy was performed on permanent tunneled catheters in 10.8% of the patients and using an arteriovenous fistula for the rest of the patients. Catheter-handling protocols are currently applied in all centers. Standard heparin (multi-dose ampoules) was used in 64.1% of the patients and LMWH in the rest. Surface sterilization after each HD session was applied routinely as per protocol. Patients in whom the hepatitis virus was positive were treated in isolated rooms and with separated dialysis machines for B, C and B+C infected patients. All HD staff members were negative for HBV and HCV markers. Statistical Analysis Data were collected and analyzed using the SPSS v.15 software suite (SPSS Inc., Chicago, Ill., USA). Data are presented as mean ± standard deviations for continuous variables with Gaussian distribution, median (interquartile range) for continuous variables without Gaussian distribution or percentages for categorical variables. The lower and upper limits of the 95% confidence intervals (CI), used to estimate the prevalence, were calculated according to Wilson’s procedure for variables with Poisson distribution. Moreover, the 95% CI for odds ratio (OR) was calculated according to the mid-p method for binomial distributions. To assess the significance of the differences between groups, the Student t-test (means, Gaussian populations), Mann-Whitney-U test (medians, non-Gaussian populations), Chi-square for trend (proportions) and log-rank test (differences between survival curves and hazard ratio) were used. Continuous variable distributions were tested for normality using the Shapiro-Wilk test, and for equality of variances using Levene’s test. Correlations and regression strength were evaluated using Pearson’s correlation coefficient, and its statistical significance was assessed using t-distribution’s test. For evaluating the involvement of more confounding factors in the survival prognosis, Cox proportional hazard regression models using the backward stepwise method and a removal probability of 0.05 were built. We included in the model all univariate predictors for mortality and the HV infection status. A p value of
