| Objectives:To compare the efficacy and safety of sofosbuvir plus ledipasvir with and without RBV in treating patients with genotype 1 chronic hepatitis C by a meta-analysis.Methods:We searched pubmed,SpringerLink,EMBASE,The Cochrane Library,Medline,Science Direct databases for RCTs,which comparing sofosbuvir plus ledipasvir with and without RBV in treating CHC genotype 1 patients from December 2013 to November 2016.Then we extracted data,assessed methodology quality,and analyzed the data by meta-analysis with RevMan 5.0 software.The primary outcomes was sustained virological response at 12 weeks post-treatment(SVR12)and adverse events.The secondary outcomes included virologic relapse and breakthrough,discontinuation caused by adverse events,and five common adverse events.Results:Seven studies involving 2626 patients with genotype 1 chronic hepatitis C were included in the meta-analysis.1.There was no significant difference in SVR12 between the LED+SOF group and the LED+SOF+RBV group(RR=1.00,95%CI 0.99～1.01,P=0.99).In the subgroup analysis,SVR12 in the LED+SOF+RBV group was not statistically superior to the LED+SOF group at 8 weeks(RR=1.00,95%CI 0.96～1.05,P=0.87),12 weeks(RR=0.99,95%CI 0.97～1.01,P=0.53)and 24 weeks(RR=0.99,95%CI 0.97～1.01,P=0.49).The addition of RBV did not significantly increase the SVR12 in naive treatment patients without cirrhosis(RR=1.03,95%CI 0.99～1.07,P=0.20)and previously treated patients with cirrhosis(RR=0.99,95%CI 0.93～1.05,P=0.66).2.There was no significant difference in virologic breakthrough and relapse rate between the LED+SOF group and the LED+SOF+RBV group(RR=1.35,95%CI 0.81-2.25,P=0.25).In the subgroup analysis,virologic breakthrough and relapse rate in the LED+SOF+RBV group was not statistically superior to the LED+SOF group at 8 weeks(RR=1.33,95%CI 0.58～3.02,P=0.50)and 24 weeks(RR=1.51,95%CI 0.25～9.05,P=0.65),but significantly lower virologic breakthrough and relapse rate can be found in the therapy with RBV for the patients who received 12 weeks treatment(RR=2.32,95%CI 1.02～5.25,P=0.04).The addition of RBV did not significantly increase the virologic breakthrough and relapse rate in naive treatment patients without cirrhosis(RR=0.87,95%CI 0.40～1.91,P=0.93)and previously treated patients with cirrhosis(RR=1.23,95%CI 0.50-3.03,P=0.66).3.Compared to LED+SOF,LED+SOF+RBV therapy had significantly higher occurrence rate of all adverse events(RR=0.88,95%CI 0.84-0.92,P<0.00001).4.There was no significant difference in the incidence of discontinuation between the LED+SOF group and the LED+SOF+RBV group(RR=0.67,95%CI 0.26～1.70,P=0.40).5.The meta-analysis showed a statistically significant higher occurrence rate of fatigue(RR=0.60,95%CI 0.41-0.86,P = 0.006),nausea(RR=0.51,95%CI 0.41～0.62,P<0.00001),insomnia(RR=0.43,95%CI 0.30～0.60,P<0.00001)and rash(RR=0.36,95%CI 0.27～0.49,P<0.00001)for the LED+SOF+RBV therapy,but there was no significant difference in the occurrence rate of headache between the LED+SOF group and the LED+SOF+RBV group(RR=0.77,95%CI 0.59～1.02,P＝0.07).Conclusion:1.The efficacy of LED+SOF is not inferior to LED+SOF+RBV in patients with genotype 1 chronic hepatitis C regardless of different treatment time and history,but the addition with RBV reduced virologic breakthrough and relapse rate for 12 week.2.Compared to LED+SOF,LED+SOF+RBV therapy had significantly higher occurrence rate of all adverse events. |
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