Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome

Allegretti, Andrew S.; Israelsen, Mads; Krag, Aleksander; Jovani, Manol; Goldin, Alison; Schulman, Allison R.; Winter, Rachel; Gluud, Lise Lotte

doi:10.1002/14651858.cd005162.pub4

Cited by 45 publications

(52 citation statements)

References 46 publications

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“…Moreover, patients who responded to treatment with terlipressin plus albumin showed better survival than nonresponders to treatment; 65,66 moreover, in three meta-analyses of randomised trials, the use of terlipressin was associated with a significant improvement in short-term survival in all patients. 22,73,74 However, it should be noted that all these studies were performed in patients with HRS-1, defined according to the old classification of ICA, that is, a baseline sCr >2.5 mg/dl. Finding that a higher baseline value of sCr is definitively an independent predictor of no response to the vasoconstrictor treatment 34,35 was one of the main reasons that led the ICA to introduce the new definition of ''HRS-AKI" (Box 1).…”

Section: What Is New In the Treatment Of Hepatorenal Syndrome?mentioning

confidence: 99%

“…[18][19][20][21] The favourable response of half of patients with HRS to the administration of systemic vasoconstrictors plus intravenous albumin has been considered proof of this pathophysiological mechanism. 21,22 In recent years, many concepts have been changed in the setting of HRS. First, the Hepatology community has abandoned the traditional definition of AKI in favour of the new one, defining it as an absolute increase in sCr of ≥0.3 mg/dl from baseline or a percentage increase of ≥50% from baseline.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document

Angeli

García–Tsao

Nadim

et al. 2019

Journal of Hepatology

321

299

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Renal dysfunction is a common, life-threatening complication occurring in patients with liver disease. Hepatorenal syndrome (HRS) has been defined as a purely ''functional" type of renal failure that often occurs in patients with cirrhosis in the setting of marked abnormalities in arterial circulation, as well as overactivity of the endogenous vasoactive systems. 4,5 In 2007, the International Club of Ascites (ICA) classified HRS into types 1 and 2 (HRS-1 and HRS-2). 5 HRS-1 is characterised by a rapid deterioration of renal function that often occurs because of a precipitating event, while HRS-2 is a moderate and stable or slowly progressive renal dysfunction that often occurs without an obvious precipitant. Clinically, HRS-1 is characterised by acute renal failure while HRS-2 is mainly characterised by refractory ascites. Nevertheless, after these two entities were first described, new concepts, definitions, and diagnostic criteria have been developed by nephrologists for renal dysfunction in the general population and hospitalised patients. In particular, the definitions and characterisation of acute kidney injury (AKI), acute kidney disease and chronic kidney disease have been introduced/refined. 6 Accordingly, a debate among hepatologists of the ICA led to a complete revision of the nomenclature and diagnosistic criteria for HRS-1, which was renamed HRS-AKI. 7 Additionally, over recent years, greater granularity has been gained regarding the pathogenesis of HRS; it is now increasingly recognised that it is not a purely ''functional" entity with haemodynamic derangements, but that systemic inflammation, oxidative stress and bile salt-related tubular damage may contribute significantly to its development. That is, HRS has an additional structural component that would not only make traditional diagnostic criteria less reliable, but would explain the lack of response to pharmacological treatment with vasoconstrictors plus albumin that correlates with a progressive increase in inflammation. Because classification, nomenclature, diagnostic criteria and pathogenic theories have evolved over the years since the traditional classification of HRS-1 and HRS-2 was first described, it was considered that all these novel aspects be reviewed and summarised in a position paper. The aim of this position paper authored by two hepatologists (members of ICA) and two nephrologists involved in the study of renal dysfunction in cirrhosis, is to complete the re-classification of HRS initiated by the ICA in 2012 and to provide an update on the definition, classification, diagnosis, pathophysiology and treatment of HRS.

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Section: What Is New In the Treatment Of Hepatorenal Syndrome?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document

Angeli

García–Tsao

Nadim

et al. 2019

Journal of Hepatology

321

299

View full text Add to dashboard Cite

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“…However, the cumulative responders (irrespective of treatment) had improved survival compared with non‐responders in both studies, which is unsurprising given reversal of HRS is associated with reduced mortality. Reduction in mortality in patients treated with terlipressin for HRS was recently addressed in a Cochrane review published in 2017 with data included from nine large high‐quality RCTs and an analysis of 534 participants—this demonstrated a reduction in mortality in patients with HRS treated with terlipressin compared with placebo/no intervention with a risk ration of 0.85 (95% confidence interval 0.73 to 0.98) and a number needed to treat for an additional beneficial outcome to prevent one death of 10.…”

Section: Terlipressin For Hepatorenal Syndromementioning

confidence: 99%

Terlipressin: Current and emerging indications in chronic liver disease

Papaluca

Gow

2018

J of Gastro and Hepatol

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Terlipressin is an analogue of vasopressin that has potent vasoactive properties and has been available for use in most countries for nearly two decades. It has both established roles and emerging indications in the management of complications of decompensated chronic liver disease. We explore historic and emerging literature regarding the use of terlipressin for a range of indications including hepatorenal syndrome, portal hypertensive bleeding, and disruptions in sodium homeostasis. Novel methods of infusion-based terlipressin administration including the beneficial effect in reduction of adverse events are explored, in addition to new indications for the use of terlipressin in decompensated cirrhosis in an outpatient setting.Terlipressin is an analogue of vasopressin that has potent vasoactive properties and has been available for use in most countries worldwide for nearly two decades. Terlipressin acts through the V1a receptors, which are located predominately on vascular smooth muscle within the splanchnic circulation, resulting in splanchnic vasoconstriction.1 The terlipressin-induced splanchnic vasoconstriction gives rise to increased renal blood flow and has beneficial effects on hepatorenal syndrome (HRS) while at the same time reducing portal pressure and playing a role in reducing the risk of portal hypertensive bleeding.These unique effects of the drug have translated into terlipressin playing a crucial role in the management of HRS and variceal bleeding for many years. Over more recent times, there has been an expansion of the indications for terlipressin usage and a broadening in the methods available for drug delivery. Its established roles and emerging indications will be examined in this review.

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“…Recently, only 52% of HRS patients have responded to therapy with terlipressin (Møller et al, 2000;Fabrizi et al, 2006;Gluud et al, 2010;Allegretti et al, 2017). Furthermore, few researches have reported some predictors of response to treatment in HRS patients treated with this regimen.…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome

et al. 2020

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Background and Purpose: Predictors of response to type-1 hepatorenal syndrome (HRS) therapy are urgently needed. This study's purpose is to evaluate the proposed predictors in these patients.Methods: Forty-two type-1 HRS patients with cirrhosis were treated with albumin and terlipressin. Clinical, biochemical, and demographic parameters taken at the onset of therapy and changes in endothelin-1/nitric oxide (ET-1/NO) ratio during therapy were analyzed to check their predictive value.Results: Response to treatment (serum creatinine level <1.5 mg/dL at the end of therapy) was shown in 20 patients (48%). Independent predictive variables of response to therapy were early reduction of ET-1/NO ratio ≥0.15 at day 3 of therapy and serum bilirubin baseline <8 mg/dL (area under the receiver operating characteristic curve, 0.751; P < 0.001; specificity, 55%; sensitivity, 85%). Response rates in patients with serum bilirubin level <8 and ≥8 mg/dL were 63% and 20%, respectively (P = 0.008). The corresponding values in patients with an early reduction of ET-1/NO ratio ≥0.15 and <0.15 on day 3 were 85% and 13.6%, respectively (P < 0.001).Conclusions: Early reduction of ET-1/NO ratio and lower serum bilirubin baseline can predict response to type-1 HRS therapy with albumin and terlipressin. Alternative therapy should be investigated for nonresponder type-1 HRS patients.Abbreviations: HRS, hepatorenal syndrome; ET-1/NO ratio, endothelin-1/nitric oxide ratio; GFR, glomerular filtration rate; PMN, polymorphonuclear; SBP, spontaneous bacterial peritonitis; IVCCI, inferior vena cava collapsibility index; CBC, complete blood count; MELD, Model for End-Stage Liver Disease.Abdel-Razik et al.ET-1/NO Ratio in HRS Frontiers in Pharmacology | www.frontiersin.org January 2020 | Volume 11 | Article 9

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Terlipressin versus placebo or no intervention for people with cirrhosis and hepatorenal syndrome

Cited by 45 publications

References 46 publications

News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document

News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document

Terlipressin: Current and emerging indications in chronic liver disease

Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome

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