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Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: A network meta-analysis

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Background Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome. Objectives To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis. Search methods We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis. Selection criteria We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. Data collection and analysis Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events.We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. Main results We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to sixmonths. Overall, 59%of participants died during this period and about 35%of participants recovered fromhepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone. Therewas no evidence of a difference inmortality (22 trials; 1153 participants) atmaximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation atmaximal follow-up (four trials; 342 participants), or other features of decompensation atmaximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.




Best, L. M. J., Freeman, S. C., Sutton, A. J., Cooper, N. J., Tng, E. L., Csenar, M., … Gurusamy, K. S. (2019, September 12). Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: A network meta-analysis. Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd.

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