Effectiveness of a hepatitis B vaccination program at two tertiary hemodialysis centers

Introduction: Hemodialysis (HD) patients are at increased risk of hepatitis B infection in comparison to the general population. Despite a more intensified hepatitis vaccination regimen, response rates in HD patients are typically low. The study was conducted to quantify response rate to a new hepatitis B vaccination protocol initiated in late 2015, determine risk factors affecting response rate, and assess adherence to protocol. Methods: This retrospective chart review evaluated all HD patients eligible for hepatitis B vaccination in two large dialysis clinics from initiation of the hepatitis B protocol to July 2017. Recombinant hepatitis vaccine (Recombivax® HB) 40 μg was administered in a 3‐dose regimen at months 0, 1, and 6 to patients with hepatitis B surface antibodies (anti‐HBs) <10 mIU/mL. A repeat series was given if anti‐HBs levels remained below 10 mIU/mL after the first series. A booster dose was given if anti‐HBs titers fell below 10 mIU/mL after initial response to a second series vaccination. Findings: Of 411 patients at the two HD centers, 142 patients received hepatitis B vaccination with a total of 168 vaccine courses given, series 1: n = 86, series 2: n = 60 and booster: n = 22. Response rates to vaccination were 61.4%, 58.3%, and 81.8%, respectively. In univariate analysis, adherence to protocol significantly affected response rate (P = 0.035). A multivariate analysis assessing response rates to series 1, 2 or booster confirmed that adherence was a significant risk factor (OR = 2.2; 95% CI 1.4–3.4; P = 0.0005). Discussion: This was the first study to examine adherence to regimen and identified adherence as an important predictor of vaccine response. Adherence is one of the few modifiable risk factors that can be optimized in an effort to improve response to hepatitis B vaccination.     

Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease

Recombivax-HB (REC) and Engerix-B (ENG) are FDA-approved vaccines for hepatitis B virus (HBV) in end-stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 mug dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer>or=10 IU/mL) were tracked for 1 year. A supplemental analysis of a one-to-one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine-related antigenemia. The difference in conversion response favoring ENG persisted in a one-to-one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23-47% of patients 1 year later, validating CDC recommendations to re-test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial.     

Occult hepatitis B virus infection of hemodialysis patients: A cross‐sectional study in a hepatitis B virus‐endemic region

Occult hepatitis B virus (HBV) infection is defined as the presence of HBV DNA in the liver tissue and/or serum of subjects seronegative for hepatitis B surface antigen (HBsAg). Occult HBV infection of hemodialysis (HD) patients is informative in terms of virus transmission, reactivation after kidney transplantation, and the progression of liver disease. However, there is little detailed information about occult HBV infection in the context of virus endemicity. We tried to investigate the seroprevalence and clinical features of occult HBV infection in HD patients in HBV‐endemic regions. We enrolled a total of 159 HD patients and 121 apparently healthy subjects at Dankook University Hospital and Jeju National University Hospital in Korea. HBsAg, anti‐HBs, anti‐HBc, and anti‐hepatitis C virus (HCV) antibody levels were measured by radioimmunoassay. Serum levels of HBV DNA were measured by real‐time polymerase chain reaction. The seroprevalence of occult HBV infection was 1.3% in HD patients and 2.5% in the healthy controls. This difference was not significant. The HBV load in all subjects with occult infection was <116 copies/mL, and all were positive for IgG anti‐HBc, regardless of the presence of anti‐HBs. None of the occult HBV‐infected subjects were co‐infected with HCV. One of the 2 HD patients with occult HBV infection had no history of blood transfusion. In this HBV‐endemic region, the seroprevalence of occult HBV infection in HD patients with a very low viral load was not significantly different from that in apparently healthy subjects.     

Hepatitis B Virus Vaccine Response in Hemodialysis: Baseline Patient Characteristics

Background: Hepatitis B virus (HBV) vaccination is recommended for all individuals with renal failure. Nevertheless, the response rate for this vaccine in hemodialysis (HD) patients is low, ranging from 50% to 80%. The goal of this study was to determine patient characteristics at the initiation of HD that influence HBV vaccine response. Methods: Patients new to HD in an urban population in the United States were retrospectively examined. Analyzed patients were HBV antibody and antigen negative and hepatitis C virus antibody negative at the start of HD, who received HBV recombinant vaccine. Nonresponse was defined as failure to seroconvert (>10 UI/L) after six deltoid intramuscular injections of vaccine. Response was defined as a lasting seroconversion (at least two consecutive positive titers) with ≤6 injections. Demographic, laboratory, and kinetic modeling data were examined. Results: A total of 33 nonresponders and 64 responders were identified. Univariate analysis demonstrated that nonresponders were older (59 vs. 51 years), had a higher prevalence of diabetes mellitus (DM) (70 vs. 39%), had lower serum albumin levels (3.2 vs. 3.3 g/dL), and had higher dry weights (84 vs. 71 kg) than responders at HD start. In addition, nonresponders had lower normalized protein catabolic rates (0.74 vs. 0.85 g/kg/day) and lower (single‐pool) spKt/V _urea values (0.95 vs. 1.19). Nonresponders had lower serum creatinine levels than responders, despite the greater dry weights. In a multiple logistic analysis model, the presence of DM, age ≥ 55 years, body weight ≥80 kg, and normalized protein catabolic rate ≤0.75 g/kg/day were associated with HBV vaccination nonresponse. At the end of the vaccination period, nonresponders versus responders continued to have lower serum albumin (3.5 vs. 3.8 g/dL) and creatinine levels (7.8 vs. 10.0 mg/dL) and spKt/V _urea (1.27 vs. 1.39). Conclusion: Hepatitis B vaccine nonresponders on HD are older, are more likely to have DM, are more malnourished, and have lower spKt/V_urea than responders. Nonresponders may also have a different body composition with a lower ratio of lean to total body mass.     

Occult hepatitis B infection in a hemodialysis population in Guilan province, northern Iran

Hemodialysis (HD) patients are vulnerable to transfusion-transmitted infections such as hepatitis B virus (HBV). HBV infection with undetectable hepatitis B surface antigens (HBsAg) is described as occult HBV and can lead to serious complications. The aim of this study was to evaluate the prevalence of occult HBV and concomitant factors in HD patients. Using a cross-sectional design, clinical and epidemiological data were obtained from May to September 2009 in 11 different HD units in Guilan province in northern Iran. After serological testing for HBV surface antigens in 514 HD patients using a third-generation enzyme-linked immunosorbent assay kit (Diapro, Milano, Italy), HBsAg-negative patients were tested for HBV DNA using a Qiagen PCR kit (Artus Qiagen GmbH, Hilden, Germany). After omission of seven HBsAg-positive patients, 507 patients were included in the study, 280 (55.2%) of whom were male and 227 (44.8%) were female. Patients ranged in age from 16 to 66 years (mean 53.2 years). No HBV DNA was detected in HBsAg-negative patients. Some 59 patients (11.6%) were anti-hepatitis C virus positive and 32 (6.3%) were hepatitis C virus positive according to polymerase chain reaction. The study results indicate that occult HBV infection is not a significant health problem in HD patients in Guilan province.     

Role of T‐regulatory cells in the response to hepatitis B vaccine in hemodialysis patients

Human disease elicits a complex array of biological processes that results in long‐term protective immunological memory to infectious agents. Chronic kidney disease is known to impair induction of sustained immunological memory to hepatitis B vaccine (HBVax) antigens. We asked the question: Does end‐stage renal disease promote changes in subtypes of regulatory T (Treg) cells that correlate with diminished amnestic response to HBVax antigen compared to healthy controls? The study design and setting was a prospective observational cohort at a veterans affairs medical center. End‐stage renal disease patients on hemodialysis (HD) were compared with individuals with self‐reported normal kidney function. All subjects received HBVax. Peripheral blood was sampled for assessment for Treg cells pre and post vaccination. CD4+ FOXP3 Treg numbers were similar between HD and healthy subjects during a 14‐day time period post vaccination. HD subjcts had lower anti‐HBSag antibody than CON (control) subjects (330 ± 108.7 vs. 663.1 ± 129.7 IU/mL; P = 0.063). Hemodialysis subjects with resting Tregs higher than the median value in our cohort demonstrated a significantly lower change in HBsAB at 30 days post booster vaccination (P = 0.030). No such relationship was found for the activated Treg subset among HD subjects, or either subset among CON subsets. In our limited comparison study of 11 HD and 8 CON subjects, Treg subsets did not differ between the two groups; but differences in the suppressive Treg numbers in the HD group could explain the altered antibody response to HBVax and is worthy of further study.     

Incidence of hepatitis C virus infection in patients on hemodialysis: A systematic review and meta‐analysis

Hepatitis C virus infection is a perennial concern for hemodialysis units because the prevalence of hepatitis C is significantly higher there than in the general population. Through a systematic review and meta‐analysis, we aim to assess the incidence rate of hepatitis C virus infection in hemodialysis units and explore its potential risk factors. Five electronic databases were used to search articles from 1990 to 2012, including PubMed, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang. A random‐effects analysis was used to estimate the overall incidence rate of hepatitis C virus infection. A subgroup analysis and meta‐regression analysis were conducted to explore factors associated with heterogeneity between studies. Twenty‐two eligible articles were found, including 23 incidence rate estimates. The overall incidence rate of hepatitis C virus infection was 1.47 per 100 patient‐years (95% confidence interval [CI] 1.14 to 1.80). In the subgroup analysis, the pooled incidence rate was 4.44 (CI 2.65, 6.23) per 100 patient‐years in the developing world and 0.99 (CI 0.66, 1.29) per 100 patient‐years in the developed world. [Correction added on 2 November 2012, after first online publication: Pooled incidence rate in the developed world has been changed.] In addition, in hemodialysis units with higher prevalence, the incidence rate of hepatitis C virus infection also tended to be higher. Meta‐regression analysis showed that the country's development level and initial HCV prevalence combined could explain 67.91% of the observed heterogeneity. The incidence rate of hepatitis C virus infection among patients on hemodialysis was significantly high. Efforts should be taken to control hepatitis C virus infection in hemodialysis units, especially in developing countries.     

Hepatitis B and C in dialysis units in Iran: changing the epidemiology

Hepatitis B (HBV) and C (HCV) viruses are the most important infections transmitted by the parenteral route in patients receiving maintenance dialysis. The prevalence varies markedly from country to country. The aim of this study is to review the efficacy of the strategies to reduce the incidence of these infections and the trend of results in Iran. As a routine, all hemodialysis patients in Iran have biannual blood samples for assessment of serum HBSAg, HBS Abs, and HCV Abs. The data are collected in the Ministry of Health. For statistical analysis, prevalence, and incidence were calculated. There is an increasing prevalence/incidence of end-stage renal disease (ESRD) in Iran, from 238/49.9 pmp in 2000 to 357/63.8 pmp in 2006. The prevalence of positive HBSAg and HCV Abs decreased from 3.8% and 14.4% in 1999 to 2.6% and 4.5% in 2006, respectively. Regarding the genotype distribution in Iran, no one was found with genotype 2. On the subject of decreasing HBV infection, our next strategy should be mandatory vaccination in dialysis centers and in the pre-ESRD period. Concerning HCV infection prevention, 2 approaches may be recommended: the first is decrease of duration of the hemodialysis period by possible early transplantation of suitable patients. The next is a strictly enforced isolation policy for HCV-positive patients, which may play a role in limiting HCV transmission in HD units, and universal precaution in dialysis units should be under constant close surveillance.     

Nightly home hemodialysis: Five and one-half years of experience in Lynchburg, Virginia

Background: Lynchburg Nephrology Dialysis Incorporated initiated a nightly home hemodialysis (NHHD) program in September 1997. As of April 30, 2003, 40 patients had completed training; 28 patients were at home and 2 patients were in training. The average age of the patients at the initiation of the home‐based therapy was 50 years, with a range of 23 to 81 years. There have been 24,239 treatments at home with a total of 84.86 patient‐years on NHHD, the longest patient for 66.7 months and the shortest for 1 month. Methods: Patients dialyzed using the Fresenius 2008H machine, 6 to 10 hr, 5 to 6 nights per week. Treatment parameters included a blood flow rate of 200 to 250 mL/min; a dialysis flow rate of 200 to 300 mL/min; and a standard dialysis solution with 2.0 mEq/L potassium, 3.0 to 3.5 mEq/L calcium concentrations, 35 mEq/L HCO₃, and 140 mEq/L sodium. The longitudinal data of each patient in the program for 1, 2, 3, 4, and 5 years were compared to the same patient's pre‐NHHD data. There were 25 patients in the program for 1 year, 19 patients for 2 years, 14 patients for 3 years, 6 patients for 4 years, and 4 patients for 5 years. Results: Statistically significant improvement occurred in all five groups' need for antihypertensive medications and phosphate binders, SF36 scores, calcium/phosphorus product, blood pressure, number of hospital admissions, and number of days of stay in the hospital. The mortality rate was 2.4% deaths per patient‐year with a 95% confidence interval of 0.9% to 9.4%. Conclusions: In a longitudinal study, NHHD showed significant improvements in patient secondary outcomes. The improvement in these secondary outcomes was associated with an improvement in mortality rate.     

Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.     

Glucose variability in maintenance hemodialysis patients with type 2 diabetes: Comparison of dialysis and nondialysis days

Introduction

Hemodialysis (HD) induces several physiological changes that can affect plasma glucose levels in patients with diabetes and in turn their glycemic control. Studies using continuous glucose monitoring (CGM) to assess glucose variations on dialysis days compared with nondialysis days report conflicting results. Here, we used CGM to examine glucose variations induced by HD in patients with type 2 diabetes.

Methods

Patients with type 2 diabetes undergoing maintenance HD were included. CGM (Ipro2®, Medtronic) was performed at baseline and Week 4, 8, 12, and 16 for up to 7 days at each visit. CGM profiles on days where participants received HD were compared with days without HD using a linear mixed model.

Findings

Twenty-seven patients were included. The median number of CGM days performed was 8 (interquartile range [IQR] 6–10) for dialysis days and 16 (IQR 12–17) for nondialysis days. The median sensor glucose was 9.4 (95% confidence interval [CI] 8.8–10.2) mmol/L on dialysis days compared with 9.5 (95% CI 8.9–10.2) mmol/L on nondialysis days (p = 0.58). Nocturnal mean sensor glucose was higher on dialysis days compared with nondialysis days: 8.8 (95% CI 8.0–9.6) mmol/L versus 8.4 (95% CI 7.7–9.2) mmol/L (p = 0.029).

Discussion

Similar median sensor glucose values were found for days on and off HD. Nocturnal glucose levels were modestly increased on dialysis days. Our findings indicate that antidiabetic treatment does not need to be differentiated on dialysis versus nondialysis days in patients with type 2 diabetes undergoing maintenance HD.     

Renal cell carcinoma sharply captured by imaging technology at an early stage in a hemodialysis patient: Usefulness of noninvasive monochrome superb microvascular imaging

It has been drawing much attention that type 2 diabetes mellitus is closely associated with increased incidence of numerous cancers and their poor prognosis. Consequently, malignancy has been recently recognized as one of diabetic complications in addition to various conventional complications. Furthermore, it is well known that the prevalence of renal cell carcinoma (RCC) is drastically increased in hemodialysis (HD) patients. Therefore, screening of RCCs in HD patients is a very important and urgent issue as there are no highly sensitive tumor markers for RCCs. Monochrome superb microvascular imaging (mSMI) is a relatively new Doppler ultrasound technique and is useful especially when evaluating very slow blood flow state, because this allows for imaging microvessels with low velocity in the absence of a contrast agent. Thus, mSMI might be also useful when contrast enhancement is not obvious on CT and/or contrast-enhanced ultrasonography using perflubutane or contrast agents are contraindicated. Moreover, it has been reported that mSMI could effectively detect vascularity of renal malignant tumor than benign renal mass in nondialysis patients. We propose that mSMI of ultrasonography could become one of the very useful methods for detecting RCCs at an early stage with high sensitivity in HD patients.     

Structure of point defects in B2 Fe-Al alloys: An atomistic study by semi-empirical simulation

We present the first results of a simulation study of point-defect properties in B2 ordered Fe-Al alloys (34% < x_Al < 52%). After examining the T = 0 K energetics of simple defects, we turn to complexes and discuss the usual hypothesis of independent elementary defects. Almost all complex defects involving an Al vacancy and an Al antisite atom in nearest neighbour position are shown to be unstable, confirming that Al vacancies are rare in these alloys. Small deviations from stoichiometry induce a change in the nature of defects: whereas on the Al-rich side, isolated Al antisite atoms dominate, Fe antisite atoms have a strong trend towards clustering on the Fe-rich side, leading to the formation of local DO₃ order.     

Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation,in vitro and in vivo evaluation

Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.     

Effect of boron concentration in Y2O3:(Eu,B) phosphor on luminescence property

Y₂O₃:(Eu,B) red phosphor was obtained by a thermal decomposition technique of a mixture of yttrium–ethylenediaminetetraacetic acid (Y–EDTA), Eu–EDTA and boric acid. The doping ratio of boron, [B]/([Y]C[Eu]), in the starting material was varied from 0 to 1. The properties of morphology, crystallization behavior, metal composition and photoluminescence of resulting Y₂O₃:(Eu,B) powder were examined. The Y₂O₃:(Eu,B) powder had spherical shape with a diameter of 1–5 mm with some hollows on the surface. No secondary cohesive particles were seen. X-ray diffractometry revealed that although the crystallinity of powder was improved with addition of small amounts of boron, it decreased with excess amounts of boron. Several peaks indexed as the impurity phases of Y₃BO₆ and YBO₃ were observed on the samples obtained under condition of excess amounts of boron. The photoluminescence intensity observed at 611 nm was dependent upon crystallinity of the sample.