A MERICAN A SSOCIATION FOR

T HE STUDY OF LIVER D I S E ASES

CORRESPONDENCE HEPATOLOGY, July 2016



FIG. 1. Portal venogram of a 72-year-old man with cirrhosis and SPSS, who undergoes a TIPS procedure with subsequent antegrade
SPSS embolization. Besides, the Amplatzer plugging device is employed for post-TIPS refractory HE. (A) A TIPS stent (black arrow)
is shown; (b) a TIPS stent (black arrow) and Amplatzer plugging device (white arrow) are shown.


available by making use of the antegrade or retrograde

approach. Therefore, more researches concerning SPSS
and post-HE are warranted.
Wenbin Wu, M.D.
Guohong Han, M.D.
Department of Liver Disease and Digestive
Interventional Radiology
Xijing Hospital of Digestive Diseases
Fourth Military Medical University
Xi’an, China
with cirrhosis and variceal bleeding. HEPATOLOGY 2015;61:1761-
1762.
2) Laleman W, Simon-Talero M, Maleux G, Perez M, Ameloot
K, Soriano G, et al. Embolization of large spontaneous porto-
systemic shunts for refractory hepatic encephalopathy: a multi-
center survey on safety and efficacy. HEPATOLOGY 2013;57:
2448-2457.
3) Kumamoto M, Toyonaga A, Inoue H, Miyakoda K, Morita Y,
Emori K, et al. Long-term results of balloon-occluded retrograde
transvenous obliteration for gastric fundal varices: hepatic deterio-
ration links to portosystemic shunt syndrome. J Gastroenterol
Hepatol 2010,25:1129-1135.

C 2015 by the American Association for the Study of Liver Diseases.

REFERENCES
1) Wu W, He C, Han G. Embolization of spontaneous splenore-
nal shunt for after-TIPS hepatic encephalopathy in a patient
Copyright V
View this article online at wileyonlinelibrary.com.
DOI 10.1002/hep.28346
Potential conflict of interest: Nothing to report.



Efficacy of Outpatient Continuous Terlipressin Infusions for

Hepatorenal Syndrome
TO THE EDITOR:
We read with interest the article by Cavallin
et al.(1) demonstrating the efficacy of continuous terli-
pressin infusions in patients with hepatorenal syn-
drome (HRS). The renal response rates obtained
were higher than those reported by Sanyal et al. with
bolus administration of terlipressin.(2) As highlighted
by Cavallin et al., a past pharmacodynamic study of
bolus terlipressin demonstrated that its effect on por-
tal pressure lasted less than 4 hours.(3) Extrapolating
these data over a 24-hour period, with standard 6-
hourly bolus dosing there may be 8 hours or more
where there is no effect of terlipressin on portal pres-
sure or renal perfusion; and this may explain the
higher renal response rates observed with continuous
infusion of the drug.

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HEPATOLOGY, Vol. 64, No. 1, 2016 CORRESPONDENCE


TABLE 1. Six Patients Treated With an Outpatient
Continuous Terlipressin Infusion
Parameter Median (Range)
Age (years) 64 (56-70)
Gender Male, n 5 6
Etiology of liver disease Alcohol, n 5 3
Hepatitis C virus, n 5 2
Primary sclerosing
cholangitis, n 5 1
MELD (at commencement of infusion) 18 (12-27)
Infusion length (days) 13 (1-50)
Creatinine at the commencement of
bolus terlipressin
Micromoles per liter 225 (175-306)
Milligrams per deciliter 2.55 (1.98-3.46)
Creatinine at the commencement of
terlipressin infusion
FIG. 1. Creatinine values before, during, and after terlipressin
Micromoles per liter 135 (106-200)
infusion. Abbreviation: Cr, creatinine.
Milligrams per deciliter 1.53 (1.20-2.26) 
Change in creatinine during infusion
Micromoles per liter 214 (210 to 238)
Milligrams per deciliter 20.16 (20.11 to 20.43) stable after successful hepatitis C treatment. The
Time to nadir creatinine on 8 (1-36) remaining two patients had the infusions ceased: one
terlipressin infusion (days) after 4 days due to bleeding from the catheter site and
Abbreviation: MELD, Model for End-Stage Liver Disease. the other after 5 days due to being deemed not suitable
for OLT. Transferring care from the hospital to the
home resulted in a cost reduction from A$1200
(US$843) to A$281 (US$197) per patient per day.
We have described the novel use of outpatient con- Our experience suggests that outpatient continuous
tinuous terlipressin infusion as a bridge to orthotopic terlipressin infusion, when used in the appropriate
liver transplantation (OLT).(4) We have now success- clinical scenario and under close supervision, is a safe,
fully used outpatient infusions in six patients with efficacious, and cost-effective means of preserving renal
HRS (Table 1 and Fig. 1). In the past these patients function in patients with terlipressin-dependent HRS
would have remained in hospital. All patients fulfilled who are awaiting OLT.
the diagnostic criteria for HRS and acute kidney injury
as defined by the International Ascites Club.(5) Due to
concerns over the upward trajectory of the creatinine, Abhinav Vasudevan, M.B.B.S.
patients were commenced on terlipressin before they Zaid Ardalan, M.B.B.S.
met the strict definition of HRS type 1. All patients Paul Gow, M.B.B.S., M.D.
initially received bolus administration of terlipressin Peter Angus, M.B.B.S., M.D.
(0.85 mg intravenously 6-hourly) to confirm efficacy Adam Testro, M.B.B.S., Ph.D.
and tolerability for a median of 6 days (range 1-21), Liver Transplant Unit Victoria
following which they were discharged home on a con- Austin Health
tinuous infusion. All patients initially received 3.4 mg Melbourne, Australia
of terlipressin per 24-hour period, with two patients
tolerating a dose reduction to 1.7 mg over 24 hours.
The reduction in dose was to achieve the lowest infu-
sion dose that maintained renal function. There were REFERENCES
no adverse events reported with the infusion. Three
1) Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P,
patients were bridged to OLT at a median of 21 days Salerno F, et al. Terlipressin plus albumin versus midodrine and
(range 1-37) from commencement of the infusion. octreotide plus albumin in the treatment of hepatorenal syndrome:
Renal function remained stable in the post-OLT a randomized trial. HEPATOLOGY 2015;62:567-574.
2) Sanyal AJ, Boyer T, Garcia-Tsao G, Regenstein F, Rossaro L,
period with a median creatinine at 3 months post-
Appenrodt B, et al. A randomized, prospective, double-blind, placebo-
OLT of 140 lmol/L (range 80-189) or 1.58 mg/dL controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroen-
(range 0.90-2.14). One patient reversed the HRS after terology 2008;134:1360-1368.
27 days of terlipressin and has subsequently remained

317
CORRESPONDENCE
3) Escorsell A, Bandi JC, Moitinho E, Feu F, Garcıa-Pagan
JF, Bosch J, et al. Time profile of the haemodynamic effects
of terlipressin in portal hypertension. J Hepatol 1997;26:621-
627.
4) Robertson M, Majumdar A, Garrett K, Rumler G, Gow P, Testro A.
Continuous outpatient terlipressin infusion for hepatorenal syndrome
as a bridge to successful liver transplantation. HEPATOLOGY 2014;60:
2125-2126.
5) Wong F, Nadim MK, Kellum JA, Salerno F, Bellomo R, Gerbes
A, et al. Working party proposal for a revised classification system
of renal dysfunction in patients with cirrhosis. Gut 2011;60:702-
709.
C 2015 by the American Association for the Study of Liver Diseases.
Copyright V
View this article online at wileyonlinelibrary.com.
DOI 10.1002/hep.28325
Potential conflict of interest: Nothing to report.
REPLY:
We appreciate the interest of Vasudevan et al. in
our article recently published in HEPATOLOGY(1) on
the use of terlipressin by continuous infusion, a
schedule we introduced in 2006 in the treatment of
hepatorenal syndrome (HRS).(2) We read with inter-
est their experience with the outpatient continuous
infusion of terlipressin in patients with HRS on the
liver transplant (LT) waiting list. However, we want
to point out some aspects regarding the applicability
of this strategy. First of all, in our experience, a
median of 6 days seems a too short period to consider
a safe discharge of patients with type 1 HRS, which
frequently presents bacterial infections and/or other
organ failures. Second, a long-term intravenous con-
tinuous infusion of terlipressin is not needed in most
responders because of the achievement of a sustained
response after withdrawal of terlipressin and albumin.
It may be suitable for patients with continuous recur-
rence of HRS after any attempt to discontinue terli-
pressin, a condition we defined in 2011 and that
occurs in 13% of HRS episodes.(3) The long-term
continuous infusion of terlipressin in outpatients may
significantly reduce the hospital stay and the cost of
management in these patients, particularly if it is
combined with a dedicated LT allocation policy.
Otherwise, effective treatment with terlipressin and
albumin, by reducing Model for End-Stage Liver
Disease score,(3) may affect the position of patients on
the waiting list, delaying LT. This is the reason we
proposed, in the setting of exceptions to Model for
318
HEPATOLOGY, July 2016
End-Stage Liver Disease score in patients with HRS,
to include long-term treatment with terlipressin and
albumin in the calculation of Model for End-Stage
Liver Disease score, as already provided for renal
replacement therapy.(4) Our proposal was accepted by
the Italian board of experts in LT and adopted in the
Italian allocation program for LT.(5) Finally, we sug-
gest a note of caution about the outpatient infusion of
terlipressin: it has potentially serious side effects.
Thus, nowadays, we think that it should be used in
hospital, under medical supervision. Waiting for the
results of larger prospective studies on the use of terli-
pressin in outpatients, possibly with an analogue
available for intramuscular or subcutaneous adminis-
tration, continuous infusion of terlipressin should be
reserved for very select outpatients with continuous
recurrence of HRS.
Marta Cavallin, M.D.
Salvatore Piano, M.D.
Paolo Angeli, M.D., Ph.D.
Unit of Hepatic Emergencies and Liver Transplantation
Department of Medicine
University of Padua
Padua, Italy
REFERENCES
1) Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P,
Salerno F, et al. Terlipressin plus albumin versus midodrine and
octreotide plus albumin in the treatment of hepatorenal syndrome:
a randomized trial. HEPATOLOGY 2015;62:567-574.
2) Angeli P, Guarda S, Fasolato S, Miola E, Craighero R, Piccolo
F, et al. Switch therapy with ciprofloxacin vs. intravenous cefta-
zidime in the treatment of spontaneous bacterial peritonitis in
patients with cirrhosis: similar efficacy at lower cost. Aliment
Pharmacol Ther 2006;23:75-84.
3) Piano S, Morando F, Fasolato S, Cavallin M, Boscato N, Boccagni P,
et al. Continuous recurrence of type 1 hepatorenal syndrome and
long-term treatment with terlipressin and albumin: a new exception to
MELD score in the allocation system to liver transplantation?
J Hepatol 2011;55:491-496.
4) Angeli P, Gines P. Hepatorenal syndrome, MELD score and liver
transplantation: an evolving issue with relevant implications for
clinical practice. J Hepatol 2012;57:1135-1140.
5) Cillo U, Burra P, Mazzaferro V, Belli L, Pinna AD, Spada M, et al. A
multistep, consensus-based approach to organ allocation in liver trans-
plantation: toward a “blended principle model.” Am J Transplant 2015;
15:2552-2561.
Copyright V
C 2015 by the American Association for the Study of Liver Diseases.
View this article online at wileyonlinelibrary.com.
DOI 10.1002/hep.28324
Potential conflict of interest: Nothing to report.