V. Dixit

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

Summary.u2002 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 145u2003608 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, Riu2003=u20030.58 (P‐value by Q‐testu2003=u20030.087). 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.

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.

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

Summary.u2002 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.

Pegylated interferon monotherapy of chronic hepatitis C in dialysis patients: Meta-analysis of clinical trials

The efficacy and safety of pegylated interferon monotherapy in patients with chronic renal failure and chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. A systematic review of the literature with a meta‐analysis of clinical trials was performed in order to assess efficacy and safety of initial pegylated interferon monotherapy in chronic renal failure patients with chronic hepatitis C. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop‐out rate (as a measure of tolerability). The random effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Sixteen clinical trials (254 unique patients) were identified, five (31%) being controlled studies; the majority (15/16u2009=u200994%) regarded patients on long‐term dialysis. The summary estimate for sustained virological response and drop‐out rate was 33% [95% Confidence Intervals (95%CI) 24–43] and 23% (95%CI, 14–33), respectively. The most frequent side‐effects requiring interruption of treatment were haematological (18%) and gastrointestinal (14%). In the group of controlled clinical trials, the summary estimate for sustained viral response and drop‐out rate was 38% (95% CI, 18–59), and 15% (95% CI, 3–26), respectively. The studies were heterogeneous with regard to sustained virological response and drop‐out rate. Pegylated IFN does not provide an added benefit in terms of virological response in comparison with standard IFN monotherapy. Tolerance to pegylated‐IFN monotherapy was unsatisfactory. Prospective trials are in progress to assess the optimal antiviral therapy for chronic hepatitis C in dialysis patients. J. Med. Virol.

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.

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

Aliment Pharmacol Ther 2011; 33: 815–821

Meta-analysis: levamisole improves the immune response to hepatitis B vaccine in dialysis patients

Backgroundu2002 Patients undergoing maintenance dialysis often fail to mount protective antibodies to hepatitis B virus surface antigen (HBsAg) following vaccination against hepatitis B virus (HBV). Some authors have suggested that levamisole improves immune response to HBV vaccine in dialysis population. However, consistent information on this issue does not exist.

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

Summary.u2002 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), Pu2003=u20030.001. The test of study heterogeneity was not significant. This difference did not persist during follow‐up (6–60u2003months 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.

Meta-Analysis: The Impact of Nutritional Status on the Immune Response to Hepatitis B Virus Vaccine in Chronic Kidney Disease

BackgroundPatients with chronic kidney disease (CKD) typically show a diminished immune response to hepatitis B virus (HBV) vaccine compared with individuals with intact kidney function. A number of inherited or acquired factors have been implicated in this suboptimal response. Patients with chronic kidney disease frequently have a compromised nutritional status; however, the impact of malnutrition on the immune response to hepatitis B virus vaccine in chronic kidney disease patients remains unclear.AimTo evaluate the influence of nutrition status on the immune response to HBV vaccine in CKD population by performing a systematic review of the literature with a meta-analysis of clinical studies.MethodsStudy-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates of impaired vaccine response across the published studies. The risk of poor serological response to HBV vaccine in chronic kidney disease population according to nutritional parameters was regarded as the most reliable outcome end-point. Only studies performing multivariate analysis in order to make adjustments for potential confounders were included.ResultsWe identified seven studies (15,172 unique patients with CKD). The serum protection rate after a full course of recombinant or plasma-derived vaccine towards HBV ranged between 40 and 86%. Aggregation of study results showed an independent and adverse effect of poor nutrition status, as mostly detected by serum albumin levels, on the protection rate after HBV vaccine course; the summary estimate for adjusted RR was 1.50 with a 95% confidence interval (CI) of 1.02, 2.21; Rixa0=xa00.01 (random-effects model). The P value for study heterogeneity was significant (Qxa0=xa00.0001). In the subgroup of patients who received HBV recombinant vaccine, the relative risk of impaired serological response after HBV vaccination was 1.63 (95% CI, 1.08, 2.45), Rixa0=xa00.90, Qxa0=xa00.00001, with poor nutritional parameters at baseline.ConclusionsAn increased risk exists of impaired serologic response to HBV vaccine response among chronic kidney disease patients having poor nutrition status. Additional studies are needed to understand better the mechanisms underlying the relationship between nutritional status and serological response to HBV vaccine among patients with CKD.

Hepatitis B virus vaccine in chronic kidney disease: Improved immunogenicity by adjuvants? A meta-analysis of randomized trials

BACKGROUNDnPatients with chronic kidney disease typically show an impaired immune response to hepatitis B virus vaccine compared with healthy individuals. A variety of inherited or acquired factors have been implicated in this diminished response. Some authors suggested a benefit with adjuvantation to improve the immunogenicity of existing HBV vaccines.nnnAIMnTo evaluate the efficacy and safety of adjuvantation for hepatitis B virus vaccine in patients with chronic kidney disease.nnnMETHODSnOnly prospective, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird with heterogeneity and subgroups analyses. The primary end-point of interest was the seroprotection rate after HBV vaccination with recombinant vaccine plus adjuvants (study group) versus recombinant vaccine alone (control group).nnnRESULTSnWe identified ten studies involving 1228 unique patients with chronic kidney disease. Pooling of study results did not show a significant increase in seroprotection rate among study (HBV recombinant vaccine plus adjuvants) versus control (HBV recombinant alone) patients; the pooled odds ratio of seroprotection rate was 1.47 (95% CI: 0.88; 2.46, NS). The pooled OR for seroresponse rate after HBV vaccine (adjuvanted recombinant vaccine versus recombinant vaccine alone) did not change in the subgroup of studies based on novel adjuvant systems (i.e., HBV-AS04 or HBV-AS02), the pooled OR was 2.22 (95% CI, 0.72; 6.78), NS. Q-test for heterogeneity being 10.819 (P=0.004).nnnCONCLUSIONSnOur meta-analysis showed that adjuvanted hepatitis B vaccine did not significantly improve the seroprotection rate in patients with renal insufficiency. These results do not support adjuvantation as an approach to increase the immunogenicity of existing recombinant vaccines towards HBV in this high-risk population.