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Lise Lotte Gluud - One of the best experts on this subject based on the ideXlab platform.
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terlipressin versus other vasoactive drugs for Hepatorenal Syndrome
Cochrane Database of Systematic Reviews, 2017Co-Authors: Mads Israelsen, Aleksander Krag, Andrew S Allegretti, Manol Jovani, Alison Goldin, Rachel W Winter, Lise Lotte GluudAbstract:Background Hepatorenal Syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that, compared with placebo, terlipressin may reduce mortality and improve renal function in people with Hepatorenal Syndrome, but we need current evidence from systematic reviews on the benefits and harms of terlipressin versus other vasoactive drugs. Objectives To evaluate the beneficial and harmful effects of terlipressin versus other vasoactive drugs for people with Hepatorenal Syndrome. Search methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and Science Citation Index Expanded; conducted manual searches of references in relevant literature; and wrote to experts and pharmaceutical companies (date of last search November 2016). Selection criteria Randomised clinical trials comparing terlipressin versus any other type of vasoactive drugs for Hepatorenal Syndrome. We allowed albumin and other cointerventions if provided equally in the comparison groups. Data collection and analysis Three authors independently extracted data. The primary outcomes were mortality, Hepatorenal Syndrome (persistent Hepatorenal Syndrome despite treatment), and serious adverse events. We conducted meta-analyses and present the results as risk ratios (RR) with 95% confidence intervals (CI). We performed sensitivity, subgroup, and Trial Sequential Analyses and evaluated bias control based on the Cochrane Hepato-Biliary Group domains. Main results We included 10 randomised clinical trials with 474 participants. The trials compared terlipressin versus noradrenaline (seven trials), octreotide (one trial), midodrine and octreotide (one trial), or dopamine (one trial). All participants in both groups received albumin as cointervention. We classified two trials at low risk of bias and eight trials at high risk of bias in the assessment of mortality and all trials at high risk of bias for remaining outcomes. In five trials, investigators specifically stated that they did not receive funding from for-profit organisations. We had no information about the funding source from the remaining five trials. Terlipressin was not superior or inferior compared with other vasoactive drugs in regard to mortality when including the two trials with a low risk of bias (RR 0.92, 95% CI 0.63 to 1.36; 94 participants, very low quality evidence) or when including all 10 trials (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). One meta-analysis including nine trials suggested a beneficial effect of terlipressin on Hepatorenal Syndrome (RR 0.79, 95% CI 0.63 to 0.99; 394 participants; I² = 26%; very low quality evidence). Due to the high mortality of Hepatorenal Syndrome, the registration of other serious adverse events is uncertain, but comparing terlipressin and other vasoactive drugs we found no significant difference (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). Several trials did not report systematically of adverse events, but terlipressin seemed to increase the risks of diarrhoea or abdominal pain, or both (RR 3.50, 95% CI 1.19 to 10.27; 221 participants; 5 trials, I² = 0%). However, Trial Sequential Analyses found insufficient evidence to support or refute any differences between interventions for all outcomes. Considering reversal of Hepatorenal Syndrome, subgroup analyses on the type of other vasoactive drugs found that terlipressin was superior compared with midodrine and octreotide (RR 0.47, 95% CI 0.30 to 0.72) or octreotide alone (RR 0.56, 95% CI 0.33 to 0.96), but each subgroup only included one small trial. None of the remaining subgroup or sensitivity analyses found differences between terlipressin and other vasoactive drugs. We downgraded the evidence to very low quality because of the high risk of bias, imprecision, and the results of the Trial Sequential Analyses. Authors' conclusions This review found insufficient evidence to support or refute beneficial or harmful effects of terlipressin and albumin versus other vasoactive drugs and albumin. Additional research is needed to evaluate if clinically meaningful differences exist between interventions.
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terlipressin for Hepatorenal Syndrome
Cochrane Database of Systematic Reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that terlipressin improves renal function in Hepatorenal Syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for Hepatorenal Syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 Hepatorenal Syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of Hepatorenal Syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 Hepatorenal Syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of Hepatorenal Syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 Hepatorenal Syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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The Cochrane Library - Terlipressin for Hepatorenal Syndrome
The Cochrane database of systematic reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that terlipressin improves renal function in Hepatorenal Syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for Hepatorenal Syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 Hepatorenal Syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of Hepatorenal Syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 Hepatorenal Syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of Hepatorenal Syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 Hepatorenal Syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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Terlipressin for Hepatorenal Syndrome.
The Cochrane database of systematic reviews, 2006Co-Authors: Lise Lotte Gluud, M S Kjaer, Erik ChristensenAbstract:Terlipressin may reverse some of the circulatory changes associated with Hepatorenal Syndrome. To assess the beneficial and harmful effects of terlipressin for Hepatorenal Syndrome. Electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Renal Group Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE were combined with scanning of bibliographies and conference proceedings, and correspondence with experts and pharmaceutical companies. Last search update was July 2006. Randomised clinical trials were included irrespective of dose or treatment duration. Included patients had type 1 or type 2 Hepatorenal Syndrome. Co-interventions were allowed if administered equally to both treatment and control groups. Data were retrieved from trial reports and correspondence with the authors of included trials. Mortality was the primary outcome. Meta-analyses were performed to calculate risk differences (RD) for binary outcomes and weighted mean differences (WMD) for continuous outcomes. Both were presented with 95% confidence intervals (CI). Due to the limited number of trials, no subgroup analyses were performed. The initial searches identified 645 potentially relevant references. Six randomised trials were eligible for inclusion. Three trials are still ongoing. Three trials with a total of 51 patients assessed terlipressin 1 mg bid for 2 to 15 days. Co-interventions included albumin, fresh frozen plasma, and cimetidine 800 mg daily. One trial reported adequate bias control assessed by randomisation and blinding. All trials reported mortality. Terlipressin reduced mortality rates by 34% (RD -0.34, 95% CI -0.56 to -0.12). The control group mortality rate was 65%. Terlipressin improved renal function assessed by creatinine clearance (WMD 21 ml/min, 95% CI 17 to 26), serum creatinine (WMD -219 micromol/l, 95% CI -244 to -194), and urine output (WMD 707 ml/day, 95% CI -212 to 1625). Adverse events included headache, abdominal pain, cardiac arrhythmia, and hypertension. Additional evidence on terlipressin for Hepatorenal Syndrome is needed before reliable treatment recommendations can be made. The dose and duration of therapy, and the influence of co-interventions remain to be established.
Paul Martin - One of the best experts on this subject based on the ideXlab platform.
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Meta-analysis: terlipressin therapy for the Hepatorenal Syndrome
Alimentary pharmacology & therapeutics, 2006Co-Authors: F Fabrizi, Vivek Dixit, Paul MartinAbstract:Summary Background The Hepatorenal Syndrome is a severe and well-known complication of end-stage liver disease, but its management is controversial. Recent reports have shown the efficacy of terlipressin therapy, a vasopressin analogue, in Hepatorenal Syndrome patients. Aim To evaluate the efficacy and safety of terlipressin in the treatment of Hepatorenal Syndrome. Methods We performed a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome (as a measure of efficacy) was the rate of responder patients (i.e. patients who had Hepatorenal Syndrome reversal after terlipressin therapy). The secondary outcomes were the rate of responders who had Hepatorenal Syndrome recurrence after terlipressin withdrawal, and the drop-out rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird with heterogeneity and sensitivity analysis. Results We identified 10 clinical trials (154 unique patients); two (20.0%) were randomized, controlled trials. The pooled rate of patients who reversed Hepatorenal Syndrome after terlipressin therapy was 0.52 (95% CI, 0.42; 0.61), P = 0.0001; I2 = 24.6%. The pooled frequency of responder patients who showed Hepatorenal Syndrome recurrence after terlipressin withdrawal was 0.55 (95% CI, 0.40; 0.69), P = 0.00001; I2 = 44.3%. The pooled rate of patients who showed side-effects to terlipressin therapy was 0.29 (95% CI, 0.17; 0.42), P
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meta analysis terlipressin therapy for the Hepatorenal Syndrome
Alimentary Pharmacology & Therapeutics, 2006Co-Authors: F Fabrizi, Vivek Dixit, Paul MartinAbstract:Summary Background The Hepatorenal Syndrome is a severe and well-known complication of end-stage liver disease, but its management is controversial. Recent reports have shown the efficacy of terlipressin therapy, a vasopressin analogue, in Hepatorenal Syndrome patients. Aim To evaluate the efficacy and safety of terlipressin in the treatment of Hepatorenal Syndrome. Methods We performed a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome (as a measure of efficacy) was the rate of responder patients (i.e. patients who had Hepatorenal Syndrome reversal after terlipressin therapy). The secondary outcomes were the rate of responders who had Hepatorenal Syndrome recurrence after terlipressin withdrawal, and the drop-out rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird with heterogeneity and sensitivity analysis. Results We identified 10 clinical trials (154 unique patients); two (20.0%) were randomized, controlled trials. The pooled rate of patients who reversed Hepatorenal Syndrome after terlipressin therapy was 0.52 (95% CI, 0.42; 0.61), P = 0.0001; I2 = 24.6%. The pooled frequency of responder patients who showed Hepatorenal Syndrome recurrence after terlipressin withdrawal was 0.55 (95% CI, 0.40; 0.69), P = 0.00001; I2 = 44.3%. The pooled rate of patients who showed side-effects to terlipressin therapy was 0.29 (95% CI, 0.17; 0.42), P < 0.0001, I2 = 66.6%. The drop-out rate was 0%. The pooled OR for mortality rate in Hepatorenal Syndrome patients who were not responders to terlipressin vs. responder patients was 5.746 (95% CI, 1.5; 21.9). We did not find any predictive factor of response to terlipressin therapy. Conclusions This meta-analysis shows efficacy and safety of terlipressin in the treatment of Hepatorenal Syndrome. However, a significant number of responder patients relapsed after terlipressin withdrawal. Further studies are in progress to address the link between terlipressin and survival in Hepatorenal Syndrome patients.
Aleksander Krag - One of the best experts on this subject based on the ideXlab platform.
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terlipressin versus other vasoactive drugs for Hepatorenal Syndrome
Cochrane Database of Systematic Reviews, 2017Co-Authors: Mads Israelsen, Aleksander Krag, Andrew S Allegretti, Manol Jovani, Alison Goldin, Rachel W Winter, Lise Lotte GluudAbstract:Background Hepatorenal Syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that, compared with placebo, terlipressin may reduce mortality and improve renal function in people with Hepatorenal Syndrome, but we need current evidence from systematic reviews on the benefits and harms of terlipressin versus other vasoactive drugs. Objectives To evaluate the beneficial and harmful effects of terlipressin versus other vasoactive drugs for people with Hepatorenal Syndrome. Search methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and Science Citation Index Expanded; conducted manual searches of references in relevant literature; and wrote to experts and pharmaceutical companies (date of last search November 2016). Selection criteria Randomised clinical trials comparing terlipressin versus any other type of vasoactive drugs for Hepatorenal Syndrome. We allowed albumin and other cointerventions if provided equally in the comparison groups. Data collection and analysis Three authors independently extracted data. The primary outcomes were mortality, Hepatorenal Syndrome (persistent Hepatorenal Syndrome despite treatment), and serious adverse events. We conducted meta-analyses and present the results as risk ratios (RR) with 95% confidence intervals (CI). We performed sensitivity, subgroup, and Trial Sequential Analyses and evaluated bias control based on the Cochrane Hepato-Biliary Group domains. Main results We included 10 randomised clinical trials with 474 participants. The trials compared terlipressin versus noradrenaline (seven trials), octreotide (one trial), midodrine and octreotide (one trial), or dopamine (one trial). All participants in both groups received albumin as cointervention. We classified two trials at low risk of bias and eight trials at high risk of bias in the assessment of mortality and all trials at high risk of bias for remaining outcomes. In five trials, investigators specifically stated that they did not receive funding from for-profit organisations. We had no information about the funding source from the remaining five trials. Terlipressin was not superior or inferior compared with other vasoactive drugs in regard to mortality when including the two trials with a low risk of bias (RR 0.92, 95% CI 0.63 to 1.36; 94 participants, very low quality evidence) or when including all 10 trials (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). One meta-analysis including nine trials suggested a beneficial effect of terlipressin on Hepatorenal Syndrome (RR 0.79, 95% CI 0.63 to 0.99; 394 participants; I² = 26%; very low quality evidence). Due to the high mortality of Hepatorenal Syndrome, the registration of other serious adverse events is uncertain, but comparing terlipressin and other vasoactive drugs we found no significant difference (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). Several trials did not report systematically of adverse events, but terlipressin seemed to increase the risks of diarrhoea or abdominal pain, or both (RR 3.50, 95% CI 1.19 to 10.27; 221 participants; 5 trials, I² = 0%). However, Trial Sequential Analyses found insufficient evidence to support or refute any differences between interventions for all outcomes. Considering reversal of Hepatorenal Syndrome, subgroup analyses on the type of other vasoactive drugs found that terlipressin was superior compared with midodrine and octreotide (RR 0.47, 95% CI 0.30 to 0.72) or octreotide alone (RR 0.56, 95% CI 0.33 to 0.96), but each subgroup only included one small trial. None of the remaining subgroup or sensitivity analyses found differences between terlipressin and other vasoactive drugs. We downgraded the evidence to very low quality because of the high risk of bias, imprecision, and the results of the Trial Sequential Analyses. Authors' conclusions This review found insufficient evidence to support or refute beneficial or harmful effects of terlipressin and albumin versus other vasoactive drugs and albumin. Additional research is needed to evaluate if clinically meaningful differences exist between interventions.
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terlipressin for Hepatorenal Syndrome
Cochrane Database of Systematic Reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that terlipressin improves renal function in Hepatorenal Syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for Hepatorenal Syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 Hepatorenal Syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of Hepatorenal Syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 Hepatorenal Syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of Hepatorenal Syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 Hepatorenal Syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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The Cochrane Library - Terlipressin for Hepatorenal Syndrome
The Cochrane database of systematic reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that terlipressin improves renal function in Hepatorenal Syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for Hepatorenal Syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 Hepatorenal Syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of Hepatorenal Syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 Hepatorenal Syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of Hepatorenal Syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 Hepatorenal Syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
Erik Christensen - One of the best experts on this subject based on the ideXlab platform.
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terlipressin for Hepatorenal Syndrome
Cochrane Database of Systematic Reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that terlipressin improves renal function in Hepatorenal Syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for Hepatorenal Syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 Hepatorenal Syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of Hepatorenal Syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 Hepatorenal Syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of Hepatorenal Syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 Hepatorenal Syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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The Cochrane Library - Terlipressin for Hepatorenal Syndrome
The Cochrane database of systematic reviews, 2012Co-Authors: Lise Lotte Gluud, Kurt Christensen, Erik Christensen, Aleksander KragAbstract:Background Clinical trials suggest that terlipressin improves renal function in Hepatorenal Syndrome, but the evidence concerning mortality is equivocal. Objectives To assess the beneficial and harmful effects of terlipressin alone or with albumin versus placebo, no intervention or albumin for Hepatorenal Syndrome. Search methods Eligible trials were identified through electronic (The Cochrane Library, MEDLINE, EMBASE and Science Citation Index databases) and manual searches until January 2012. Selection criteria Randomised clinical trials involving patients with type 1 or type 2 Hepatorenal Syndrome were included irrespective of publication status or language. Data collection and analysis The review authors independently extracted data from trial reports and undertook correspondence with the authors. Primary outcome measures included mortality, reversal of Hepatorenal Syndrome and adverse events. Intention-to-treat, random-effects model meta-analyses were performed and results were expressed as risk ratios (RR) with 95% confidence intervals (CI), and the I2 statistic provided a measure of intertrial heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed. Main results We identified six randomised clinical trials. All had high risk of bias. Five trials assessed terlipressin (with albumin in three trials) versus no intervention (with albumin in three trials) and one trial assessed terlipressin versus albumin. Data from five randomised trials on terlipressin alone (one trial) or terlipressin and albumin (four trials) were included in the review. In total, 74 of 155 (47.7%) patients randomised to terlipressin alone or terlipressin with albumin versus 98 of 154 (63.6%) patients randomised to no intervention, placebo or albumin died. Random-effects model meta-analysis found that terlipressin reduced mortality (RR 0.76, 95% CI 0.61 to 0.95). The results were stable when repeated with trials on terlipressin plus albumin, trials on patients with type 2 Hepatorenal Syndrome, and trials with a low risk of selection bias. No evidence of bias or small study effects were identified in regression analyses. In a trial sequential analysis on mortality, the cumulative Z curve approached but did not cross the monitoring boundary suggesting that the results were not stable to adjustment for sparse data and multiple comparisons. Analyses of the remaining outcome measures found that terlipressin and albumin increased the number of patients with reversal of Hepatorenal Syndrome as well as adverse events, including cardiovascular and gastrointestinal symptoms. Authors' conclusions Terlipressin may reduce mortality and improve renal function in patients with type 1 Hepatorenal Syndrome. Whether the evidence is strong enough to support the intervention for clinical practice could be debated due to the results of the trial sequential analyses. However, the outcome measures assessed are objective, which reduces the risk of bias.
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Terlipressin for Hepatorenal Syndrome.
The Cochrane database of systematic reviews, 2006Co-Authors: Lise Lotte Gluud, M S Kjaer, Erik ChristensenAbstract:Terlipressin may reverse some of the circulatory changes associated with Hepatorenal Syndrome. To assess the beneficial and harmful effects of terlipressin for Hepatorenal Syndrome. Electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Renal Group Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, and EMBASE were combined with scanning of bibliographies and conference proceedings, and correspondence with experts and pharmaceutical companies. Last search update was July 2006. Randomised clinical trials were included irrespective of dose or treatment duration. Included patients had type 1 or type 2 Hepatorenal Syndrome. Co-interventions were allowed if administered equally to both treatment and control groups. Data were retrieved from trial reports and correspondence with the authors of included trials. Mortality was the primary outcome. Meta-analyses were performed to calculate risk differences (RD) for binary outcomes and weighted mean differences (WMD) for continuous outcomes. Both were presented with 95% confidence intervals (CI). Due to the limited number of trials, no subgroup analyses were performed. The initial searches identified 645 potentially relevant references. Six randomised trials were eligible for inclusion. Three trials are still ongoing. Three trials with a total of 51 patients assessed terlipressin 1 mg bid for 2 to 15 days. Co-interventions included albumin, fresh frozen plasma, and cimetidine 800 mg daily. One trial reported adequate bias control assessed by randomisation and blinding. All trials reported mortality. Terlipressin reduced mortality rates by 34% (RD -0.34, 95% CI -0.56 to -0.12). The control group mortality rate was 65%. Terlipressin improved renal function assessed by creatinine clearance (WMD 21 ml/min, 95% CI 17 to 26), serum creatinine (WMD -219 micromol/l, 95% CI -244 to -194), and urine output (WMD 707 ml/day, 95% CI -212 to 1625). Adverse events included headache, abdominal pain, cardiac arrhythmia, and hypertension. Additional evidence on terlipressin for Hepatorenal Syndrome is needed before reliable treatment recommendations can be made. The dose and duration of therapy, and the influence of co-interventions remain to be established.
Pere Ginès - One of the best experts on this subject based on the ideXlab platform.
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Hepatorenal Syndrome: pathophysiology, diagnosis, and management
BMJ (Clinical research ed.), 2020Co-Authors: Douglas A. Simonetto, Pere Ginès, Patrick S. KamathAbstract:Hepatorenal Syndrome (HRS), the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduction in renal blood flow and glomerular filtration rate. Hepatorenal Syndrome is diagnosed when kidney function is reduced but evidence of intrinsic kidney disease, such as hematuria, proteinuria, or abnormal kidney ultrasonography, is absent. Unlike other causes of acute kidney injury (AKI), Hepatorenal Syndrome results from functional changes in the renal circulation and is potentially reversible with liver transplantation or vasoconstrictor drugs. Two forms of Hepatorenal Syndrome are recognized depending on the acuity and progression of kidney injury. The first represents an acute impairment of kidney function, HRS-AKI, whereas the second represents a more chronic kidney dysfunction, HRS-CKD (chronic kidney disease). In this review, we provide critical insight into the definition, pathophysiology, diagnosis, and management of Hepatorenal Syndrome.
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Hepatorenal Syndrome
Nature Reviews Disease Primers, 2018Co-Authors: Pere Ginès, Paolo Angeli, Mitra K Nadim, Elsa Solà, Florence Wong, Patrick S. KamathAbstract:Hepatorenal Syndrome (HRS) is a form of kidney function impairment that characteristically occurs in cirrhosis. Recent changes in terminology have led to acute HRS being referred to as acute kidney injury (AKI)-HRS and chronic HRS as chronic kidney disease (CKD)-HRS. AKI-HRS is characterized by a severe impairment of kidney function owing to vasoconstriction of the renal arteries in the absence of substantial abnormalities in kidney histology. Pathogenetic mechanisms involve disturbances in circulatory function due to a marked splanchnic arterial vasodilation, which triggers the activation of vasoconstrictor factors. An intense systemic inflammatory reaction that is characteristic of advanced cirrhosis may also be involved. The main triggering factors of AKI-HRS are bacterial infections, particularly spontaneous bacterial peritonitis. The diagnosis of AKI-HRS is a challenge because of a lack of specific diagnostic tools and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The prognosis of patients with AKI-HRS is poor, with a median survival of ≤3 months. The ideal treatment for AKI-HRS is liver transplantation in patients without contraindications. Medical therapy consists of vasoconstrictor drugs to counteract splanchnic arterial vasodilation together with volume expansion with albumin. Effective measures to prevent AKI-HRS include early identification and treatment of bacterial infections and the administration of albumin in patients with spontaneous bacterial peritonitis. Hepatorenal Syndrome (HRS) is defined as severe kidney functional impairment that occurs in patients with liver cirrhosis. This Primer discusses new diagnostic criteria of acute kidney injury in the context of HRS and also covers pathophysiology and management of this serious disorder.
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Terlipressin for Hepatorenal Syndrome: Predictors of Response
Frontiers of Gastrointestinal Research, 2010Co-Authors: Andrés Cárdenas, Pere GinèsAbstract:Hepatorenal Syndrome (HRS) is a reversible cause of renal impairment that occurs in patients with cirrhosis and ascites. The best available therapy for HRS, other than liver transplantation, is the us
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Circulatory function and Hepatorenal Syndrome in cirrhosis.
Hepatology (Baltimore Md.), 2005Co-Authors: Luis Ruiz-del-arbol, Pere Ginès, Alberto Monescillo, Carlos Arocena, Paz Valer, Víctor Moreira, José María Milicua, Wladimiro Jiménez, Vicente ArroyoAbstract:The pathogenic mechanism of Hepatorenal Syndrome is not well established. We investigated the circulatory function in cirrhosis before and after the development of Hepatorenal Syndrome. Systemic and hepatic hemodynamics and the activity of endogenous vasoactive systems were measured in 66 patients who had cirrhosis with tense ascites and normal serum creatinine levels; measurements were repeated at follow-up in 27 cases in whom Hepatorenal Syndrome had developed. At baseline, mean arterial pressure and cardiac output were significantly higher, and hepatic venous pressure gradient, plasma renin activity, and norepinephrine concentration were significantly lower in patients who did not develop Hepatorenal Syndrome compared with those presenting with this complication. Peripheral vascular resistance was decreased to the same extent in the two groups. Plasma renin activity and cardiac output were the only independent predictors of Hepatorenal Syndrome. Hepatorenal Syndrome occurred in the setting of a significant reduction in mean arterial pressure (83 +/- 9 to 75 +/- 7 mmHg; P < .001), cardiac output (6.0 +/- 1.2 to 5.4 +/- 1.5 L/min; P < .01), and wedged pulmonary pressure (9.2 +/- 2.6 to 7.5 +/- 2.6 mmHg; P < .001) and an increase in plasma renin activity (9.9 +/- 5.2 to 17.5 +/- 11.4 ng/mL . hr; P < .001), norepinephrine concentration (571 +/- 241 to 965 +/- 502 pg/mL; P < .001), and hepatic venous pressure gradient. No changes were observed in peripheral vascular resistance. In conclusion, these data indicate that Hepatorenal Syndrome is the result of a decrease in cardiac output in the setting of a severe arterial vasodilation.
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terlipressin plus albumin infusion an effective and safe therapy of Hepatorenal Syndrome
Journal of Hepatology, 2000Co-Authors: Juan Uriz, Pere Ginès, Wladimiro Jiménez, Andrés Cárdenas, Pau Sort, J Salmeron, Ramon Bataller, A Mas, M Navasa, Vicente ArroyoAbstract:Abstract Background/Aim: Ornipressin, a vasopressin analog with potent splanchnic vasoconstrictor action, has been shown to reverse Hepatorenal Syndrome. However, its usefulness in clinical practice is limited by frequent ischemic complications. The aim of this study was to assess the efficacy of terlipressin, an analog of vasopressin with a low profile of side effects, plus albumin in this condition. Methods: Nine consecutive patients with cirrhosis and Hepatorenal Syndrome were included in a pilot study of terlipressin (0.5–2 mg/4 h iv) therapy associated with iv albumin. Results: Treatment (9 days, range 5–15) was associated with a marked reduction of serum creatinine (3.9±0.7 to 1.3±0.1 mg/dl, p p p Conclusions: Terlipressin associated with albumin appears to be a safe and effective treatment of Hepatorenal Syndrome.