La infección por VHB es un factor de riesgo de enfermedad renal crónica: revisión sistemática y metaanálisis / HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis

Antecedentes El papel del virus de la hepatitis B (VHB) como factor de riesgo en la incidencia y progresión de la enfermedad renal crónica (ERC) no ha sido clarificado. Objetivo Evaluamos el impacto producido por la infección con el VHB sobre el riesgo de la ERC en la población general. Material y métodos Llevamos a cabo una revisión sistemática de la literatura médica publicada a fin de evaluar si existe, en la población adulta general, una relación entre la infección por el VHB y un aumento del riesgo de ERC. Adoptamos el modelo de efectos aleatorios de DerSimonian y Laird para proporcionar una estimación resumida del riesgo de ERC (definida por una tasa de filtración glomerular reducida y/o una proteinuria detectable) por infección con el VHB en los estudios publicados. También se realizaron metarregresiones y análisis estratificados. Resultados Recogimos 33 estudios (n=7.849.849 pacientes) publicados en 26 artículos y se realizó un metaanálisis por separado conforme a los resultados. La agrupación de los resultados de los estudios de cohortes (11 estudios, n=1.056.645 pacientes) demostró una relación entre un estatus serológico VHB positivo y el aumento de la incidencia de la ERC, con una estimación resumida para la HR ajustada con VHB en todas las encuestas del 1,40 (IC 95% 1,16-1,69; p<0,001). Se observó heterogeneidad entre estudios (valor Q: 49,5; p<0,0001). En el subconjunto de estudios transversales no se detectó relación entre el VHB y la prevalencia de la ERC (10 estudios; n=3.222.545 pacientes; OR ajustada 1,04; IC 95% 0,90-1,218; p=0,5). Los análisis de metarregresión informaron de una relación entre el estatus HBcAg positivo y la incidencia de ERC en la población general (p<0,015). Conclusiones Parece que la exposición a la infección por VHB está asociada con un aumento en el riesgo de desarrollar ERC en la población adulta general. Se están realizando estudios destinados a comprender los mecanismos responsables de dicha asociación (AU)

Background The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. Aim We evaluated the impact of infection with HBV on the risk of CKD in the general population. Material and methods We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. Results We retrieved 33 studies (n=7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n=1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P<.001). Between-study heterogeneity was noted (Q value, 49.5, P<.0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n=3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P=.5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P<.015). Conclusions It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way (AU)

HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis.

BACKGROUND: The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. AIM: We evaluated the impact of infection with HBV on the risk of CKD in the general population. MATERIAL AND METHODS: We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. RESULTS: We retrieved 33 studies (n = 7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n = 1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P < .001). Between-study heterogeneity was noted (Q value, 49.5, P < .0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n = 3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P = .5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P < .015). CONCLUSIONS: It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way.

HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis. / La infección por VHB es un factor de riesgo de enfermedad renal crónica: revisión sistemática y metaanálisis.

BACKGROUND: The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. AIM: We evaluated the impact of infection with HBV on the risk of CKD in the general population. MATERIAL AND METHODS: We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. RESULTS: We retrieved 33 studies (n=7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n=1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P<.001). Between-study heterogeneity was noted (Q value, 49.5, P<.0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n=3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P=.5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P<.015). CONCLUSIONS: It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way.

On the possibility of using X-ray Compton scattering to study magnetoelectrical properties of crystals.

This paper discusses the possibility of using Compton scattering--an inelastic X-ray scattering process that yields a projection of the electron momentum density--to probe magnetoelectrical properties. It is shown that an antisymmetric component of the momentum density is a unique fingerprint of such time- and parity-odd physics. It is argued that polar ferromagnets are ideal candidates to demonstrate this phenomenon and the first experimental results are shown, on a single-domain crystal of GaFeO3. The measured antisymmetric Compton profile is very small (≃ 10(-5) of the symmetric part) and of the same order of magnitude as the statistical errors. Relativistic first-principles simulations of the antisymmetric Compton profile are presented and it is shown that, while the effect is indeed predicted by theory, and scales with the size of the valence spin-orbit interaction, its magnitude is significantly overestimated. The paper outlines some important constraints on the properties of the antisymmetric Compton profile arising from the underlying crystallographic symmetry of the sample.

Diffuse multiple scattering.

A new form of diffraction lines has been identified, similar to Rutherford, Kikuchi and Kossel lines. This paper highlights some of the properties of these lines and shows how they can be used to eliminate the need for sample/source matching in Lonsdale's triple convergent line method in lattice-parameter determination.

Antiviral therapy (pegylated interferon and ribavirin) of hepatitis C in dialysis patients: meta-analysis of clinical studies.

Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long-term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long-term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta-regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long-term dialysis; such approach should be considered the current standard of care for HCV-infected individuals on regular dialysis.

Hepatitis C virus infection and glomerular disease.

The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) is well established and remains an area of intense research. HCV infection is associated with a large spectrum of histo-pathological lesions in both native and transplanted kidneys. The frequency of kidney damage in HCV-infected patients appears low even if is not fully detailed. The most frequent HCV-associated renal lesion is type I membrano-proliferative glomerulonephritis, usually in the context of type II mixed cryoglobulinemia. Various approaches have been tried for the treatment of HCV-related glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Antiviral treatment of HCV-associated glomerulonephritis has shown encouraging results. Immunosuppressive therapy is particularly recommended for cryoglobulinemic kidney disease. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. Some evidence on rituximab therapy for HCV-related cryoglobulinemic glomerulonephritis exists but several questions related to its use need to be addressed.

Meta-analysis of observational studies: hepatitis C and survival after renal transplant.

Recent evidence has shown that anti-HCV-positive serologic status is significantly linked to lower patient and graft survival after renal transplant, but conflicting results have been given on this point. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on all-cause mortality and graft loss after RT. The relative risk of all-cause mortality and graft loss was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effect pooled estimates for mortality and graft loss with HCV across the published studies. We identified eighteen observational studies involving 133 530 unique renal transplant recipients. The summary estimate for adjusted relative risk (aRR) of all-cause mortality was 1.85 with a 95% confidence interval (CI) of 1.49; 2.31 (P < 0.0001); heterogeneity statistics, Ri = 0.87 (P-value by Q-test = 0.001). The overall estimate for adjusted RR of all-cause graft loss was 1.76 (95% CI, 1.46; 2.11) (P < 0.0001), heterogeneity statistics, Ri = 0.65 (P-value by Q-test = 0.001). Stratified analysis did not change meaningfully these results. Meta-regression showed that living donor rate had a favourable influence on patient (P = 0.031) and graft survival (P = 0.01), whilst diabetes mellitus having a detrimental role on patient survival (P = 0.001). This meta-analysis of observational studies supports the notion that HCV-positive patients after RT have an increased risk of mortality and graft loss. Further studies are in progress to understand better the mechanisms underlying the relationship between HCV and mortality or graft dysfunction after renal transplant.

MnSb2O6: a polar magnet with a chiral crystal structure.

Structural and magnetic chiralities are found to coexist in a small group of materials in which they produce intriguing phenomenologies such as the recently discovered Skyrmion phases. Here, we describe a previously unknown manifestation of this interplay in MnSb(2)O(6), a trigonal oxide with a chiral crystal structure. Unlike all other known cases, the MnSb(2)O(6) magnetic structure is based on corotating cycloids rather than helices. The coupling to the structural chirality is provided by a magnetic axial vector, related to the so-called vector chirality. We show that this unique arrangement is the magnetic ground state of the symmetric-exchange Hamiltonian, based on ab initio theoretical calculations of the Heisenberg exchange interactions, and is stabilized by out-of-plane anisotropy. MnSb(2)O(6) is predicted to be multiferroic with a unique ferroelectric switching mechanism.

Lamivudine treatment for hepatitis B in dialysis population : case reports and literature review.

It is well known that chronic hepatitis B plays a detrimental role on survival in patients on long-term dialysis and after kidney transplantation. The advent of nucleos(t)ide analogues offers the opportunity to change the natural history of hepatitis B in patients with chronic kidney disease. We report our experience on lamivudine use in two patients with HBV-related liver disease on long-term dialysis. At the beginning, both the patients were HBsAg positive and HBeAg positive with high viral load; after long-term lamivudine therapy, clearance of HBV viremia from serum was observed in both. Raised aminotransferase levels fell into the normal range and one patient experienced clearance of HBsAg by anti-HBV therapy. Tolerance to lamivudine was satisfactory and lamivudine resistance was not detected. Information on antiviral therapy with lamivudine in HBsAg positive patients on regular dialysis is extremely limited; we identified by an extensive review of the literature five studies with a total of 38 unique patients, most of them being renal transplant candidates. Lamivudine proved to be effective as the clearance of HBV viraemia from serum ranged between 56% and 100% ; the clearance of HBeAg from serum was less evident (between 37.5% and 100%). No significant side-effects due to lamivudine were observed and emergence of lamivudine-resistant strains was observed in two (5%) patients. Only a minority of patients experienced HBsAg loss (13%). We conclude that anti-HBV treatment with a nucleoside analogue such as lamivudine gives satisfactory results in some patients on long-term dialysis. Clinical trials are in progress to assess efficacy and safety of last-generation nucleos(t)ide analogues for anti-HBV therapy in dialysis population.

Interferon therapy of acute hepatitis C in dialysis patients: meta-analysis.

The efficacy and safety of antiviral therapy in patients with acute hepatitis C on long-term dialysis remains unclear, although a number of small clinical studies have been published addressing this issue. We evaluated the efficacy and safety of interferon therapy in chronic dialysis patients with acute hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR, as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eight clinical studies (173 unique patients), three (37.5%) being controlled clinical trials (CCTs). Among CCTs, the viral response was much more common in study (patients on antiviral therapy) than control (patients who did not receive therapy) groups; the pooled odds ratio of SVR being 27.06, 95% Confidence Intervals (95% CI), 9.26; 79.1 (P = 0.00001). No difference in the dropout rate between study and control patients was shown, odds ratio = 0.920 (95% CI, 0.367; 1.92), NS. Pooling all study results (n = 8 studies) demonstrated that the summary estimate for SVR and dropout rate was 58% (95% CI, 38; 77) and 9% (95% CI, 4; 14), respectively. The most frequent side-effects requiring interruption of the treatment were flu-like symptoms (n = 4, 18%), followed by haematological changes and loss to follow-up. A strong relationship between increasing age and reported dropout rate was recognized (P = 0.001). The studies were heterogeneous with regard to SVR but not to dropout rate. Our meta-analysis of CCTs showed that the viral response after antiviral therapy was more common than the spontaneous viral clearance in dialysis patients with acute hepatitis C. Pooled analysis demonstrated that IFN-based therapy of acute hepatitis C in dialysis populations gives SVR in around one half of patients. These results support IFN-based therapy for acute hepatitis C in patients on maintenance dialysis.

Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality?

Recent evidence has been accumulated showing that anti-HCV-positive serologic status is significantly associated with lower survival in dialysis populations, but the mechanisms underlying this negative relationship are still unclear. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus (HCV) infection on all-cause and disease-specific mortality of patients on regular dialysis. The relative risk of all-cause, cardiovascular and liver disease-related mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random effect pooled estimates for mortality with HCV across the published studies. We identified fourteen observational studies involving 145 608 unique patients on long-term dialysis. Pooling of study results demonstrated that anti-HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all-cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25-1.47. Stratified analysis showed that the adjusted RR for liver disease-related death was 3.82 (95% CI, 1.92; 7.61); heterogeneity statistics, R(i) = 0.58 (P-value by Q-test = 0.087). The adjusted RR for cardiovascular mortality was 1.26 (95% CI, 1.10; 1.45); no heterogeneity was found (NS). This meta-analysis of observational studies indicates that anti-HCV-positive patients on dialysis have an increased risk of either liver or cardiovascular disease-related mortality compared with anti-HCV-negative patients. Further studies are in progress to understand better the link between HCV and cardiovascular risk among patients on maintenance dialysis.

Hepatitis C virus and the immunological response to hepatitis B virus vaccine in dialysis patients: meta-analysis of clinical studies.

It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection.

Femtoscale magnetically induced lattice distortions in multiferroic TbMnO3.

Magneto-electric multiferroics exemplified by TbMnO(3) possess both magnetic and ferroelectric long-range order. The magnetic order is mostly understood, whereas the nature of the ferroelectricity has remained more elusive. Competing models proposed to explain the ferroelectricity are associated respectively with charge transfer and ionic displacements. Exploiting the magneto-electric coupling, we used an electric field to produce a single magnetic domain state, and a magnetic field to induce ionic displacements. Under these conditions, interference between charge and magnetic x-ray scattering arose, encoding the amplitude and phase of the displacements. When combined with a theoretical analysis, our data allow us to resolve the ionic displacements at the femtoscale, and show that such displacements make a substantial contribution to the zero-field ferroelectric moment.

Viral hepatitis in renal transplantation.

Chronic viral hepatitis remains common in the hemodialysis (HD) and renal transplantation population although measures to limit spread of hepatitis infection in HD units have markedly reduced its prevalence. Our review focuses on the current management of hepatitis B and C infections in renal transplant candidates before and after renal transplantation.

Meta-analysis: the impact of diabetes mellitus on the immunological response to hepatitis B virus vaccine in dialysis patients.

BACKGROUND: Patients on maintenance dialysis typically show a suboptimal immune response to hepatitis B virus vaccine compared with the non-uraemic population. A variety of inherited or acquired factors have been implicated in this diminished response. It is well known that patients with diabetes mellitus have a compromised immune system, and diabetic nephropathy is an important cause of chronic kidney disease. However, the impact of diabetes mellitus on the immune response to HBV vaccine in patients receiving long-term dialysis remains unclear. AIM: To evaluate the influence of diabetes mellitus on the immune response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies. METHODS: We used the random effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective antibody against hepatitis B surface antigen at completion of vaccine schedule in the diabetic vs. the nondiabetic dialysis individuals. RESULTS: We identified 12 studies involving 1002 unique patients on long-term dialysis. Aggregation of study results showed a significant decrease in response rates among the diabetic vs. the nondiabetic patients [pooled odds ratio=0.52 (95% CI 0.38-0.71)]. The P-value was 0.29 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. CONCLUSIONS: Our meta-analysis showed a clear association between diabetes mellitus and impaired response to hepatitis B virus vaccine in individuals on long-term dialysis. Such a relationship is biologically plausible. Vaccination schedules with adapted vaccine doses and frequent serum testing for loss of immunity against hepatitis B virus should be considered in patients on maintenance dialysis with diabetes mellitus.

Combined antiviral therapy of hepatitis C virus in dialysis patients: meta-analysis of clinical trials.

The efficacy and safety of combined interferon (IFN) plus ribavirin in patients on long-term dialysis and chronic hepatitis C remains unclear, although a number of small clinical trials have addressed this issue. We evaluated the efficacy and safety of combination antiviral therapy (conventional or pegylated interferon plus ribavirin) 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); 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 10 clinical studies (151 unique patients), one (10%) of which was a controlled clinical trial. Most (97.4%) patients were on long-term haemodialysis. The summary estimate for SVR and drop-out rate was 56% [95% Confidence Intervals (95% CI) 28-84] and 25% (95% CI, 10-40), respectively. The most frequent side effects requiring interruption of treatment were anaemia (26%) and heart failure (9%). These results occurred irrespective of type of interferon (conventional or peg-IFN, peg-IFNalfa-2a or alfa-2b), trial design (controlled or cohort study), or clinical characteristics of patients (naïve, nonresponders or relapsers). The studies were heterogeneous with regard to SVR and drop-out rate. Combination antiviral therapy (interferon plus ribavirin) gives encouraging results in terms of efficacy and safety among dialysis patients even if the limited number of patients enrolled in our meta-analysis hampers definitive conclusions.

Intradermal vs intramuscular vaccine against hepatitis B infection in dialysis patients: a meta-analysis of randomized trials.

Chronic dialysis patients are at risk of contracting hepatitis B virus infection and have a diminished immune response to hepatitis B virus vaccine. Recent reports support intradermal administration of hepatitis B virus vaccine in patients on regular dialysis but the efficacy and safety of this approach remain unclear. We conducted a meta-analysis of randomized, controlled clinical trials to compare seroprotection achieved by intradermal vs intramuscular hepatitis B vaccine, in patients on maintenance dialysis. Meta-analysis of data from 718 adults (14 trials) on long-term dialysis demonstrated that intramuscular hepatitis B vaccination was less likely to achieve seroprotection than intradermal vaccination, the pooled odds ratio was 0.454 (95% CI, 0.3; 0.67), P = 0.001. The test of study heterogeneity was not significant. This difference did not persist during follow-up (6-60 months after completing vaccine schedule), the pooled odds ratio being 0.718 (95% CI, 0.36; 1.47), NS. Some evidence of significant heterogeneity including publication bias was present but stratified analysis in various subgroups showed that this issue did not meaningfully change our results. Intradermal hepatitis B vaccine was safe and well tolerated. We conclude that intradermal hepatitis B vaccine induces a superior response rate compared to intramuscular route at completion of vaccine cycle, despite a lower vaccine dose. No significant advantage was found over longer follow-up. It remains unclear whether the higher seroprotection rate achieved with intradermal route translates into a lower frequency of de novo hepatitis B among patients on maintenance dialysis.