联合抗病毒治疗透析HCV的meta(2011)

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

F.Fabrizi,1,2V.Dixit,2P.Martin2and P.Messa11Division of Nephrology and Dialysis,Maggiore Hospital,IRCCS Foundation,Milano,Italy;and2Division of Hepatology,School of Medicine,University of Miami,Miami,FL,USA

Received August2010;accepted for publication September2010

SUMMARY.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 virologi-cal 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 identified10 clinical studies(151unique 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 was56%[95%Confidence Intervals(95% CI)28–84]and25%(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(naı¨ve, nonresponders or relapsers).The studies were heterogeneous with regard to SVR and drop-out http://www.mianfeiwendang.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.

Keywords:dialysis,hepatitis C,interferon,meta-analysis, ribavirin.

INTRODUCTION

Chronic hepatitis C virus(HCV)infection remains prevalent in the haemodialysis population despite elimination of HCV from the blood supply,reflecting,in part,nosocomial spread within haemodialysis units[1,2].Although there is increasing concern about the detrimental effect of HCV infection on survival in patients with chronic kidney disease (CKD),therapy of hepatitis C in this population remains challenging.

The treatment of HCV in patients on chronic haemodial-ysis is predicated on the premise that HCV is associated with decreased patient survival.The association between anti-HCV positive serologic status and diminished survival in the dialysis population is already established[3]even if an accurate assessment of the natural history of HCV in these patients is difficult[1].A recent meta-analysis(seven observational studies enrolling11589patients on mainte-nance dialysis)showed that the summary estimate for adjusted relative risk(RR)of all-cause mortality with anti-HCV was1.34with a95%confidence interval of1.13–1.59 [3].Liver dysfunction has been implicated in a lower sur-vival of seropositive patients;the summary estimate for RR of liver-related mortality with anti-HCV was3.75(95%CI, 1.93;17.99)[3].These results are consistent with evidence from other sources.A large survey of patients on dialysis in three continents reported an association between anti-HCV positive serologic status and increased mortality(RR,1.17; P£0.02)[reviewed in ref.4].

It had been suggested that mono-therapy with conven-tional or peg-IFN yields inferior responses in dialysis patients with chronic hepatitis C[4,5].Experience with combined antiviral therapy[interferon(IFN)plus ribavirin]in patients with CKD and hepatitis C is limited.The primary goal of our study was to synthesize the available evidence on the toler-ability and efficacy of combined antiviral therapy(conven-tional or peg-IFN plus ribavirin)in CKD patients with

Abbreviations:CKD,chronic kidney disease;EBR,end-of-treatment

biochemical response;HCV,hepatitis C virus;IFN,interferon;OTR,

on-treatment response;PCR,polymerase chain reaction;RR,relative

risk;SBR,sustained biochemical response;SVR,sustained virologi-

cal response.

Correspondence:Dr Fabrizio Fabrizi,Divisione Nefrologica,Ospedale

Maggiore,Pad.Croff,Via Commenda15,20122,Milano,Italy.

E-mail:fabrizi@policlinico.mi.it

Journal of Viral Hepatitis,2011,18,e263–e269doi:10.1111/j.1365-2893.2010.01405.x Ó2010Blackwell Publishing Ltd

联合抗病毒治疗透析HCV的meta(2011)相关文档

最新文档

返回顶部