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Unlabelled: Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival., Conclusion: Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS., (© 2015 by the American Association for the Study of Liver Diseases.)

Hepatorenal syndrome (HRS) is a severe complication that often occurs in patients with cirrhosis and ascites. HRS is a functional renal failure that develops mainly as a consequence of a severe cardiovascular dysfunction which is characterized by an extreme splanchnic arterial vasodilation and a reduction of cardiac output. HRS may develop in two clinical types: as an acute and rapidly progressive renal failure (AKI-HRS) or as chronic and not progressive renal failure (CKD-HRS). Several small studies and some randomized control studies have been published on the use of terlipressin plus albumin in the treatment of HRS, mainly on AKI-HRS. Terlipressin plus albumin was shown to improve renal function in almost 35-45% of patients with AKI-HRS, as well as to improve short-term survival in these patients. Terlipressin was most commonly used by intravenous boluses moving from an initial dose of 0.5-1 mg every 4 h to 3 mg every 4 h in the case of a nonresponse. In other studies, terlipressin was also given by continuous intravenous infusion. Thus, the best way to administer terlipressin in the treatment of HRS has not yet been defined. α-Adrenergic drugs, such as intravenous norepinephrine or oral midodrine plus subcutaneous octreotide, administered with albumin have also been used in the treatment of AKI-HRS, with promising results. However, we need further studies in order to define whether they can represent a real therapeutic alternative. In conclusion, available data are sufficient to state that the use of terlipressin plus albumin has really changed the management of HRS. Nevertheless, some crucial unsolved issues still exist, in particular: (a) how to predict nonresponse to treatment, (b) how to manage nonresponse to treatment and (c) how to consider the response in those patients who are candidates for liver transplant in the priority allocation process., (© 2015 S. Karger AG, Basel.)

Unlabelled: The aim of this study was to evaluate the effect and molecular mechanism of albumin infusion on cardiac contractility in experimental cirrhosis with ascites. Cardiac contractility was recorded ex vivo in rats with cirrhosis and ascites and in control rats after the injection in the caudal vein of albumin, saline, or hydroxyethyl starch (HES). Gene and protein expression of β-receptors and pathways involved in their intracellular signaling such as Gα(i2) protein (Gα(i2)), adenylate cyclase 3 (Adcy3), protein expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS), were evaluated in cardiac tissue in both groups. Phosphorylation and membrane-translocation of the cytosolic components of nicotinamide adenine dinucleotide phosphate (NAD(P)H)-oxidase and translocation of nuclear factor kappa B (NF-κB) were also evaluated. After saline intravenous injection, cardiac contractility was significantly reduced in rats with cirrhosis as compared to control rats (P < 0.01). This was associated with: (1) increased expression of protein Gα(i2) (P < 0.05), TNF-α (P < 0.05), iNOS (P < 0.05); (2) increased NAD(P)H-oxidase activity (P < 0.05); (3) increased nuclear translocation of NF-κB (P < 0.05); and (4) lower expression of Adcy 3 (P < 0.05) in cardiac tissue of rats with cirrhosis. After albumin injection cardiac contractility (P < 0.01), protein expression of TNF-α, iNOS, Gα(i2), and Adcy3, NAD(P)H-oxidase activity and nuclear translocation of NF-κB in cardiac tissue of rats with cirrhosis were reversed to control levels (P < 0.05). HES injection did not modify cardiac contractility and nuclear translocation of NF-κB in cardiac tissue of rats with cirrhosis., Conclusion: Albumin exerts a positive cardiac inotropic effect in rats with cirrhosis and ascites counteracting the negative effects of oxidative stress- and TNF-α-induced activation of NF-κB-iNOS pathway and oxidative stress-induced alteration of β-receptor signaling., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background & Aims: The recurrence of type 1 hepatorenal syndrome has been described in up to 20% of responders to terlipressin and albumin after the discontinuation of the treatment. Subsequent recurrence of type 1 hepatorenal syndrome may require long-term treatment with terlipressin and albumin., Methods: We describe our experience of long-term administration of terlipressin as a bridge to LT in three patients with cirrhosis and recurrent type 1 hepatorenal syndrome. For all three patients we requested an "early transplant" which is an option recognized in our country to reduce waiting times for liver transplantation., Results: All three patients were transplanted within 2 months of onset of hepatorenal syndrome. All patients are still alive and none of them have developed chronic kidney disease., Conclusions: The outcomes of these patients suggest that long-term treatment with terlipressin and albumin is effective and well tolerated in patients with continuous recurrence of type 1 hepatorenal syndrome and, therefore, should be considered an absolute priority criterion in the allocation system for liver transplantation., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: In patients with cirrhosis, the clinical benefit of the treatment with human albumin for ascites is debated, and no data are available regarding refractory ascites. In this study, in patients with cirrhosis and refractory ascites, we assessed the effect of long‐term albumin administration on emergent hospitalization and mortality. Methods: Seventy patients with cirrhosis and refractory ascites, followed at the Unit of Internal Medicine and Hepatology, University and General Hospital of Padova, Italy, were included into the study. Forty‐five patients were non‐randomly assigned to receive long‐term administration of human albumin at the doses of 20 g twice per week (n = 45), in addition to standard medical of care (SOC), and compared to those followed according to SOC. Patients were followed up to the end of the study, liver transplantation or death. Results: The cumulative incidence of 24‐month mortality was significantly lower in patients treated with albumin than in the group of patients treated with SOC (41.6% vs 65.5%; P = 0.032). The period free of emergent hospitalization was significantly longer in patients treated with long‐term administration of albumin (P = 0.008). Analysing separately the causes of inpatient admission, patients treated with albumin showed a reduction in the incidence of overt hepatic encephalopathy, ascites, spontaneous bacterial peritonitis (SBP) and non‐SBP infections. In addition, a non‐significant trend towards a reduced probability of hepatorenal syndrome was observed. Conclusion: In patients with cirrhosis and refractory ascites, long‐term treatment with albumin improves survival and reduces the probability of emergent hospitalizations. See Editorial on Page 45 [ABSTRACT FROM AUTHOR]