Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: Relationship of serum creatinine to hemodynamics

Abstract

Background & Aims Administration of terlipressin plus albumin is effective in reversing type 1 HRS as compared to albumin alone. However, only about 1/3 of patients respond to treatment, therefore, predictors of response and survival would help identify the patients most likely to benefit from treatment. Methods We analyzed our controlled trial of terlipressin vs. placebo (Gastroenterology 2008;134:1360) to define factors predictive of a response and to correlate hemodynamic changes to changes in renal function. Results Single variant analysis showed treatment with terlipressin, MELD score, and baseline serum creatinine to be predictive of HRS reversal. Alcoholic hepatitis, baseline serum creatinine, and MELD score were predictive of survival. When treatment was not considered as a variable, only baseline serum creatinine predicted HRS reversal. Baseline serum creatinine, presence of alcoholic hepatitis, and Child-Pugh score were also predictive of survival on multivariate analysis. The rise in mean arterial pressure (MAP) following terlipressin administration was not predictive of HRS reversal. However, in those who achieved HRS reversal from terlipressin, there was a significant rise in MAP from beginning to end of treatment. Conclusions The most consistent predictor of response to terlipressin and of survival is the baseline serum creatinine. Patients most likely to benefit from terlipressin have earlier onset renal failure (i.e. serum creatinine <5.0 mg/dl). A sustained rise in MAP is required for HRS reversal. As MAP is a surrogate marker for the hyperdynamic circulation, it is only with improvement in the hyperdynamic circulation that HRS reversal is observed.

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies

“…Our observations regarding factors predictive of HRS reversal and survival essentially confirm what has been observed in previous studies,22, 23, 24, 25, 26, 27 with the exception of the absence of a precipitating cause for HRS‐1, absence of prior rifaximin use in the terlipressin group, and male sex in the placebo group – all new observations. The absence of prior rifaximin use as a factor predictive of HRS reversal in the terlipressin group is of interest; it is possible that patients without prior rifaximin exposure are less ill than those receiving rifaximin.…”

“…For the placebo group, only the absence of alcoholic hepatitis and male sex were predictive of both longer transplant‐free survival and longer overall survival. While absence of alcoholic hepatitis is a known predictive factor for better survival,22 the finding of male sex as a predictor should be examined further. Overall survival at day 90 was significantly lower in females than in males; however, females receiving terlipressin showed a trend towards improved survival compared with those receiving placebo, and the survival estimate was similar to that for males.…”

Keeping high model for end‐stage liver disease score liver transplantation candidates alive

“…Overall, approximately one-third of HRS type 1 patients in 2 large controlled clinical trials responded to terlipressin. 43 Although overall survival was not changed, improved renal function before transplant makes peritransplant and posttransplant management easier, 44 and improved renal function before transplant improves posttransplant renal function and decreases mortality. 45 Dialysis is used in patients with HRS but usually as a bridge to LT.…”

Acute kidney injury in patients with chronic liver disease

“…This leads to ignore patients with less increased SCr though they are already presenting HRS and could receive early treatment and benefit from improved outcomes. In 2011, a study by Boyer et al [26] found that in cirrhotic patients with HRS, initial SCr was an independent predictor of the probability to get a response to terlipressin, and also to survive at 3 mo. In this study, every 1 mg/dL of increase of SCr was associated with an increase of 50% of the risk of death.…”