Original article
Pancreas, biliary tract, and liver
Association Between Grade of Acute on Chronic Liver Failure and Response to Terlipressin and Albumin in Patients With Hepatorenal Syndrome

https://doi.org/10.1016/j.cgh.2018.01.035Get rights and content

Background & Aims

Type 1 hepatorenal syndrome (HRS) is the most high-risk type of renal failure in patients with cirrhosis. Terlipressin and albumin are effective treatments for type 1 HRS. However, the effects of acute on chronic liver failure (ACLF) grade on response to treatment are not clear. We aimed to identify factors associated with response to treatment with terlipressin and albumin in patients with type 1 HRS (reduction in serum level of creatinine to below 1.5 mg/dL at the end of treatment) and factors associated with death within 90 days of HRS diagnosis (90-day mortality).

Methods

We performed a retrospective analysis of 4 different cohorts of consecutive patients with HRS treated with terlipressin and albumin from February 2007 through January 2016 at medical centers in Europe (total, 298 patients). We analyzed demographic, clinical, and laboratory data collected before and during treatment; patients were followed until death, liver transplantation, or 90 days after HRS diagnosis.

Results

Response to treatment was observed in 53% of patients. Of patients with grade 1 ACLF, 60% responded to treatment; among those with grade 2 ACLF, 48% responded, and among those with grade 3 ACLF, 29% responded (P < .001 for comparison between grades). In multivariate analysis, baseline serum level of creatinine (odds ratio, 0.23; P = .001) and ACLF grade (odds ratio, 0.63; P = .01) were independently associated with response to treatment. Patient age (hazard ratio [HR], 1.05; P < .001), white blood cell count (HR, 1.51; P = .006), ACLF grade (HR, 2.06; P < .001), and no response to treatment (HR, 0.41; P < .001) associated with 90-day mortality.

Conclusion

In a retrospective analysis of data from 4 cohorts of patients treated for type 1 HRS, we found ACLF grade to be the largest determinant of response to terlipressin and albumin. ACLF grade affects survival independently of response to treatment. New therapeutic strategies should be developed for patients with type 1 HRS and extrarenal organ failure.

Section snippets

Patients

The study includes 4 different cohorts of consecutive patients with HRS treated with terlipressin and albumin. Some patients were included in prospective investigations already published.4, 5, 10, 13 The first cohort includes patients evaluated from February 2007 to January 2016 at the University Hospital of Padova (Italy), the second cohort includes patients evaluated from July 2009 to December 2015 at the Liver Unit, Hospital Clinic of Barcelona (Spain), the third cohort includes patients

Study Population

Two-hundred and ninety-eight patients with cirrhosis and HRS were included in the study. Supplementary Table 1 illustrates the clinical characteristics of the patients. HRS was associated with bacterial infections in 169 patients (68 with SBP). The most common extrarenal organ failure was liver failure (27%), followed by coagulation failure (13%), brain failure (7%), and respiratory failure (2%). A total of 179 patients (60%) had ACLF-1, 91 (31%) ACLF-2, and 28 (9%) ACLF-3. The characteristics

Discussion

Our study, which represents the largest investigation on the pharmacological treatment of HRS, confirms the 2 major findings so far described. The first is that the combination of terlipressin and albumin is effective resolving HRS in approximately 50% of patients. The second is that baseline sCr or early improvement in sCr are accurate predictors of treatment response and patient survival. It has been proposed that once severe HRS develops, ischemic tubular lesions or renal hypoperfusion

References (21)

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Conflicts of interest These authors disclose the following: Mauro Bernardi: CLS consultant and speaker for Behring GmbH and Baxter Healthcare SA; speaker for PPTA Europe, Grifols SA, Octpharma AG, Gilead Sciences and AbbVie Italia. Alexander Gerbes: Advisor and speaker for CSL Behring GmbH and Grifols SA. Bernhard Scheiner: travel support from Gilead. Pere Ginès: research funding from Ferring Pharmaceuticals, Grifols SA, and Sequana Medical. Advisory Boards for Noorik, Ikaria, Ferring Pharmaceuticals, Promethera and Sequana Medical. Paolo Angeli: Advisory Board for Sequana Medical AG and BioVie Inc. Research funding from Grifols SA. The other Authors have nothing to disclose. The remaining authors disclose no conflicts.

Funding Elsa Solà is a recipient of a grant “Joan Rodés” from Asociación Española para el Estudio del Higado (AEEH) and a grant from Scietat Catalana de Digestologia. Jonel Trebicka is supported by grants from the Deutsche Forschungsgemeinschaft (SFB TRR57), European Union’s Horizon 2020 Research and Innovation Programme (No 668031) and Cellex Foundation. Pere Gines is a recipient of an ICREA Academia Award. The EASL CLIF Consortium is supported by an unrestricted grant from Grifols.

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