A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis.

BACKGROUND: Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients. METHODS: We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks. RESULTS: Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P < .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4-2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5-409.3) mIU/mL and 7.2 (2.0-26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P < .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16-11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent. CONCLUSIONS: Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients. CLINICAL TRIALS REGISTRATION: NCT02621112.

Vaccination in patients with chronic kidney disease-Review of current recommendations and recent advances.

Hepatitis B virus (HBV), influenza, pneumococcus and herpes zoster are important infections which could result in significant morbidity and mortality in patients with chronic kidney disease (CKD). While seroconversion rates after vaccination are often lower in CKD patients compared with healthy adults due to impaired innate and adaptive immunity, vaccinations for HBV, influenza, pneumococcus and herpes zoster are generally effective in reducing the transmission and/or severity of these infections. Practical issues that have an impact on the efficacy of vaccination in the CKD population include the timing, dose, schedule of vaccination, the route of administration, and adjuncts applied at time of vaccination. This review discusses the vaccination regimens and the efficacy of HBV, influenza, pneumococcus and zoster vaccines in CKD patients, and highlights recent advances in enhancing vaccine seroconversion rates.

Management of hepatitis B reactivation in patients with lupus nephritis.

Hepatitis B is endemic in many Asian countries and immunosuppression may precipitate hepatitic flare. There is little data on the treatment of hepatitis B in patients with systemic lupus erythematosus. We monitored serial transaminase and HBV DNA levels in our HBsAg-positive patients with a history of lupus nephritis and instituted anti-viral treatment in patients who showed virological reactivation. This retrospective pilot study reports the data with this pre-emptive management strategy. Amongst 228 patients with lupus nephritis, eight (3.51%) were HBsAg-positive and five had received Lamivudine treatment for hepatitis B. In two patients the virological flares were preceded by lupus flares that necessitated an increase in immunosuppressive treatment. Median HBV DNA level was 1.9 x 10(7) copies/mL (range 1.2 x 10(4)-1.0 x 10(9) copies/mL) at baseline, and it decreased by 2-5 logs after treatment. Four patients had abnormal transaminase levels at baseline, with mean alanine aminotransferase at 125.0 +/- 67.4 U/L, and all achieved normalisation after 3-24 months (median 13 months) of treatment. Discontinuation of Lamivudine treatment was attempted in three patients after 9-15 months. In one patient treatment was recommenced because of virological flare. For the remaining two patients in whom treatment was not interrupted, one showed sustained viral suppression and one developed drug resistance. All antiviral treatments were well-tolerated. These results indicate the importance of serial monitoring of HBV DNA and transaminase levels, and prompt anti-viral therapy, in the management of HBsAg-positive lupus patients. Also, it may be feasible to discontinue treatment in stable patients to avoid the selection of drug-resistant variants.

A cluster of rapidly growing mycobacterial peritoneal dialysis catheter exit-site infections.

In this case series, a cluster of 5 consecutive peritoneal dialysis patients with atypical mycobacterial exit-site infections in a single center within 20 months are described. Clinical features, treatment, and outcomes are discussed. Most patients had been treated with prolonged systemic antibiotic therapy for recurrent bacterial exit-site infections in the preceding months, and all had used topical gentamicin ointment for exit-site infection treatment or prophylaxis. It is postulated that this might have predisposed them to atypical mycobacterial exit-site infection as a result of selection pressure on uncommon organisms.

Cystatin C assay for the detection of renal dysfunction in Chinese renal transplant recipients.

BACKGROUND: Accurate and rapid assessment of kidney function in patients after renal transplantation is of major significance. We investigated whether cystatin C can accurately reflect creatinine clearance over the entire range of kidney graft function. The performance of serum cystatin C as a screening marker of reduced creatinine clearance in renal transplantation was evaluated and compared to serum creatinine. METHODS: Serum cystatin C, serum creatinine and creatinine clearance were measured in 103 adult renal transplant recipients. The cystatin C assay was performed using particle-enhanced immunonephelometry. RESULTS: We demonstrated a significant linear correlation between 1/cystatin C and creatinine clearance over the entire range of transplant function, comparable to that of creatinine. Cystatin C detected reduced creatinine clearance with higher sensitivity of 92.9% (95% CI 80.5-98.4%) than serum creatinine, 71.4% (95% CI 55.4-84.3%). From the receiver operating characteristic (ROC) plots, serum cystatin C is superior to serum creatinine at 90% and 95% sensitivity. CONCLUSIONS: Serum cystatin C accurately reflects creatinine clearance over the entire range of transplant kidney function and is more efficacious than serum creatinine to detect reduced creatinine clearance in renal transplant recipients.

Risk factors and outcome of contamination in patients on peritoneal dialysis--a single-center experience of 15 years.

OBJECTIVE: Contamination is an important risk factor for peritoneal dialysis (PD)-related peritonitis. The present study outlines the clinical characteristics and outcomes of PD patients experiencing touch contamination. METHODS: We reviewed the case records of PD patients from 1995 to 2010. Patients who experienced contamination of their PD system were identified and stratified into "dry" and "wet" contamination groups. Risk factors, microbiology, and clinical outcomes were compared. RESULTS: Of 548 episodes of touch contamination, 246 involved dry contamination, and 302, wet contamination. After contamination, 17 episodes of peritonitis (3.1%) developed; all episodes occurred in the wet contamination group (p < 0.001). The incidence of peritonitis after wet contamination was 5.63%. Prophylactic antibiotics significantly reduced the risk of peritonitis (1 of 182 episodes, p < 0.001). Half the patients experiencing peritonitis had either culture-negative or staphylococcal episodes, and most of those episodes responded to intraperitoneal antibiotics. In 2 patients, peritonitis was attributable to Pseudomonas, and in 3, to Acinetobacter. In these latter patients, outcomes were less favorable, with catheter removal being required in 4 of the 5 episodes. CONCLUSIONS: The overall rate of peritonitis was low after contamination. Wet contamination was associated with a much higher risk of peritonitis. Prophylactic antibiotics after wet contamination were effective in preventing peritonitis.

Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients.

Cytokine dysregulation is an important factor underlying the immune unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients. This study investigated the relationship between monocyte-derived interleukin-6 (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using flow cytometry (cytoflow) after whole blood culture. According to their previous response to hepatitis B vaccination, 40 renal transplant recipients were divided into two groups of 20 patients. The percentage of CD 14+ monocytes stained positive for intracellular IL-6 or IL-10 was measured using flow cytometry after 4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The percentage of CD 14+/IL-6+ cells after incubation in vitro for 4 h was lower in the responders compared to the non-responders and controls (27.15+/-8.93 vs 35.47+/-9.95, P=NS; and 37.06+/-10.89, P<0.05 respectively). The staining intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h, there were a significantly higher percentage of CD 14+/IL-10+ positive cells in the responders compared to the non-responders (41.87+/-18.39 vs 27.55+/-17.25, P<0.05). These results indicate that alteration of intracellular cytokine profile in activated monocytes distinguishes the HBV vaccination responders from the non-responders among renal transplant recipients. The capacity to upregulate monocyte IL-10 production in this subset of patients may modulate the immune responsiveness and effectively assists in mounting a positive response to HBV vaccination.

Prevalence and significance of hepatitis GB virus-c/hepatitis G virus viremia in a large cohort of patients with chronic hepatitis B infection, with chronic hepatitis C infection, and on renal replacement therapy in Hong Kong.

A total of 455 patients were recruited to study the prevalence of hepatitis GB virus-C/hepatitis G virus viremia in Hong Kong. There was no significant increase in the prevalence of hepatitis GB virus-C viremia in asymptomatic hepatitis B virus- and hepatitis C virus-infected patients compared to that of controls (1.56% and 7.14%, respectively, vs 3.85%, both P = NS). Renal patients as a whole had a significantly higher prevalence of hepatitis GB virus-C viremia compared to that of controls (13.95% vs 3.85%, P = 0.0271). The duration of the replacement therapy, especially for patients with peritoneal dialysis was associated with a higher chance of hepatitis GB virus-C viremia. Among renal patients, renal transplanted patients had the highest prevalence of hepatitis GB virus-C viraemia (19.1%) probably because of a higher susceptibility as a result of immunosuppression. However, hepatitis GB virus-C viraemia did not cause liver biochemistry derangement in renal transplanted patients.