| Objective:The effectiveness and safety of different treatments for type I hepatorenal syndrome were analyzed by network meta-analysis,and the best treatments were obtained.Methods:According to Cochrane’s search strategy,the literatures collected from 1998 to 2021 in major Chinese and English databases were searched,including Cochrane Library,Embase,Pub Med,Science Direct,CBM,CNKI,WANFANG MED ONLINE,VIP Paper Check System,Baidu Academic,Google Academic,etc.According to the established inclusion and exclusion criteria,clinic randomized controlled trials and case-control studies were accepted in searches of several drug therapy for hepatorenal syndrome,and the literatures were searched and screened,and then the final included literatures were evaluated for quality and data extraction.Clinic randomized controlled trial were evaluted by Cochrane collaboration’s tool for assessing risk of bias version 5.1.0.And the Newcastle-Ottawa Scale which was for assessing the quality of nonrandomised studies was carried out.Reviews Manger 5.4.1software,R language software 4.1.3 and R Studio 1.1.463 were used in statistical complement each other,and the pairwise,internal,inter-group and overall statistical heterogeneity were analized,while network meta-analysis were operated by ADDIS 1.16.8software.Results:A total of 18 randomized controlled studies and 3 case-control studies were included,all of which were HRS-I,with a total of 1560 patients.There were 7 articles about terlipressin+albumin compared with(placebo+albumin)/albumin,6 articles about terlipressin+albumin compared with norepinephrine+albumin,2 articles about octreotide+midodrine+albumin compared with terlipressin+albumin,and 2 articles about octreotide+midodrine+albumin compared with norepinephrine+albumin,albumin and octreotide+albumin respectively.The research baselines were basically consistent.The results of heterogeneity test showed that the pairwise heterogeneity test of each index was satisfactory,and there was heterogeneity in the closed-loop part of the network diagram,but the overall consistency was well.Meta-analysis results of direct comparison of schemes: in terms of the effective rate of creatinine reduction,mean creatinine reduction,mean urine output increase,mean arterial pressure increase,mean serum sodium increase and incidence of adver se events,terlipressin + albumin scheme was superior to(placebo + albumin)or al bumin scheme[(OR:3.16,95% CI:2.20-4,P<0.00001),(MD:193.29,95%CI:28.39-358.18,P=0.02),(MD:803.18,95%CI:454.05-1152.30,P<0.00001),(MD:3.35,95%CI:2.01-4.68,P<0.00001),(MD:2.12,95%CI:0.22-4.01,P=0.03),(OR:3.71,95%CI:2.00-6.91,P<0.00001),r espectively].Survival rate of terlipressin + albumin scheme similar to(placebo + al bumin)/albumin scheme(OR:1.17,95%CI: 0.87-1.57,P=0.45).Sensitivity analysis was ca rried out on the literature with high heterogeneity.In the regimen of terlipressin +albumin and(placebo+albumin)or albumi-n alone,Neri 2007 literature was exclude d from the comparison of the average cre-atinine decrease and Solanki 2003 literatu re was excluded from the average arterial pressure increase.In terms of the effective rate of creatinine reduction,average creatinine reducti on,average urine output increase,average arterial pressure increase and average ser um sodium increase,the efficacy of terlipressin + albumin compared with norepineph rine + albumin [(OR:1.43,95%CI:0.93-2.2,P<0.00001),(MD :-12.18,95% CI:-35.27-10.92,P=0.03),(MD:803.18,95%CI:454.05-1152.30,P<0.00001),(MD:3.35,95%CI:2.01-4.68,P<0.00001),(MD:-82.7,95%CI:-200.28-34.88,P=0.03),respectively].In terms of incide nce of adverse events and survival rate,the efficacy of terlipressin+albumin was hi gher than that of norepinephrine+albumin[(OR:1.67,95%CI :1.08-2.58,P=0.02),(OR:3.37,95% CI:1.51-7.41,P<0.03),respectively].Among them,the literature on the co mparative survival rate of terlipressin+albumin and norepinephrine+albumin were het erogeneous and would not be merged.Compared with terlipressin+albumin and octreotide+midodrine+albumin,its OR and95%CI of creatinine reduction was 5.49(2.18,13.78),and P value <0.05,its OR and 95%CI of survival rate was 2.41(0.55,10.46),and P value=0.24.Compared with octreotide +midodrine + albumin,its OR and 95%CI of creatinine reduction was 4.669(1.51,14.32),and P value < 0.05;its OR and 95%CI of survival rate was 1.48(0.54,4.10),and P value = 0.44;its MD and 95%CI of mean creatinine reduction was-245.84(-476.86,-14.83),and P value=0.04;its OR and 95%CI of mean urine volume was 266.94(-33.53,567.40),and P value =0.08.its OR and 95%CI of increasing mean arterial pressure was 3.58(-1.85,9.02),P value =0.20.Creatinine reduction were significantly higher with octreotide+midodrine+albumin than with(placebo+albumin)or albumin alone(OR: 6.33,95%CI :1.35-29.72).There were no heterogeneity among the above documents,so they should be merged.In the mixed analysis,in terms of creatinine reduction efficiency,the efficacy of terlipressin+albumin and norepinephrine+albumin regimen were similar,and its O R and 95%CI was 1.00(0.52,1.82);Norepinephrine+albumin was superior to octreotide+midodrine+albumin,and its OR and 95%CI was 4.08(1.29,13.11);Norepinephr ine+albumin was superior to octreotide+midodrine+albumin,and its OR and 95%CI is 6.17(2.23,17.11).In terms of survival rate and average creatinine decrease,there were no statistical difference among the schemes involved.In the indirect compari son scheme,dopamine+furosemide+albumin was better than octreotide+albumin in th e average creatinine decrease,and its MD and 95%CI was 599.56(453.97,744.46);Norepinephrine+albumin was superior to octreotide+albumin,and its MD and 95%CIwas 561.88(457.59,665.30);Octreotide+albumin was superior to placebo+albumin/al bumin,and its MD and 95%CI was 505.49(371.13,637.14);In the average increase of urine volume,norepinephrine+albumin was better than placebo+albumin/albumin alone,and its MD and 95%CI was 615.70(184.36,1128.01),with statistical differe nces.There were no statistical difference between the schemes that can be indirectl y compared in creatinine reduction efficiency,survival rate,average arterial pressure increase and serum sodium increase.Conclusion:Terlipressin or norepinephrine combined with albumin treatment for type I hepatorenal syndrome are the most effective treatments for creatinine decrease rate in ranking,which is significantly superior to the triple regimen of octreotide combined with midodrine and albumin.As creatinine decrease average value and survival rate,the ranking of curative effect of norepinephrine combined with albumin or terlipressin combined with albumin are better than that of the triple regimen of octreotide combined with midodrine and albumin. |
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