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Cheung et al. Hepatorenal syndrome before liver transplantation

and obstructive uropathy. Urinary output, sodium, the use of vasopressor plus volume expansion with
[6]
osmolality and red blood cells, and serum sodium were intravenous albumin improves prognosis of HRS. A
included as minor criteria [Table 1]. These criteria were significant proportion of patients was successfully
subsequently revised in 2007 to improve accuracy and bridged to liver transplantation. [9,13-16] Human serum
applicability. Minor criteria were excluded. Ongoing albumin has been introduced as a plasma expander
[7]
bacterial infection without septic shock was no longer since 1940 and it has been proved useful in the
an exclusion criterion [Table 1]. management of HRS. The additive effects provided
[17]
by vasoconstrictors and albumin infusion improve
Two types of HRS have been described. Type-1 HRS is outcome compared to monotherapy with either agent.
[18]
characterized by acute onset and rapidly progressing A meta-analysis has demonstrated that increments of
kidney failure with a doubling of serum creatinine 100 g in cumulative albumin dose were associated
(corresponding to a 50% reduction of creatinine with a significantly increased survival, which provides
clearance) in less than 2 weeks. The prognosis is evidence on the important role of albumin in improving
poor, with only 10% of patients surviving longer than outcome of treating HRS. [19]
90 days. Type-2 HRS presents as a less severe and
more gradual decline in renal function associated with The most commonly used vasopressor is terlipressin.
refractory ascites. The differential diagnosis between Terlipressin is a prohormone of lysine-vasopressin
the two types is based on the rate of progression and (three glycyl residues and lysine-vasopressin). The
extent of renal impairment. [3,8] In this review, we mainly glycyl residues are cleaved from the prohormone by
focus on type-1 HRS as it is more clinically relevant endothelial peptidases, allowing prolonged release
in terms of strategies bridging to liver transplantation. of lysine-vasopressin. [20,21] This mechanism enables
Treatment of type-2 HRS with terlipressin and divided-dose administration by prolonging the half-life
albumin does not appear to have beneficial effects of terlipressin, in contrast to the need for continuous
either in pretransplantation or in posttransplantation infusion as with vasopressin. Terlipressin acts on the V1
outcomes. [9] receptors expressed on vascular smooth muscle cells
in the splanchnic circulation. The vasoconstrictive
[22]
According to the IAC criteria, acute renal failure is effect corrects the circulatory dysfunction and
defined as an increase in serum creatinine (sCr) of ≥ intrarenal vasoconstriction, which lowers the levels
50% from baseline to a final value > 1.5 mg/dL (133 mol/L). of renin and serum creatinine and improves the urine
However, the threshold value of 1.5 mg/dL has been output. As a result of breaking the vicious cycle, the
challenged. Meanwhile, new definition of acute renal kidney regains its normal self-regulatory function.
[15]
failure, now termed acute kidney injury (AKI), has been Gluud et al. performed a meta-analysis in 2012
developed and validated in patients without cirrhosis. involving 6 randomized controlled trials of terlipressin
Combining the emerging evidence and consensus (with or without albumin) vs. placebo, with a total of
of the experts, the IAC revised the criteria of AKI in 309 patients. Use of terlipressin was associated with
patients with cirrhosis (type-1 HRS) in 2015. In the reduced mortality with a relative risk of 0.76 (95% CI
[10]
0.61-0.95). Concurrent use of terlipressin and albumin
new definition, AKI is defined as a sCr increase of ≥ increased the number of patients with reversal of HRS.
0.3 mg/dL (26.5 umol/L) within 48 h or of ≥ 50% from
baseline within 7 days [Table 1]. Three stages of AKI Side-effects of terlipressin include abdominal cramps
and responses to treatment were also defined. The and diarrhea, cardiac tachyarrhythmia and chest pain,
implementation of the new criteria is to allow earlier as well as cyanosis and livedo reticularis. Ischemia
treatment of patients with type-1 HRS, which may lead of bowel or skin and extremities is one of the rare
to a better outcome instead of having to wait until the complications. The adverse effects of terlipressin may
[23]
sCr reaches ≥ 2.5 mg/dL. [11] be minimized by means of intravenous infusion rather
than bolus injections as shown in a recent randomized
STRATEGIES TO BRIDGE TO LIVER controlled study in Italy. Although most commonly
[24]
TRANSPLANTATION used and studied, terlipressin is expensive and
unavailable in many countries. Other vasoconstrictive
Medical treatment aims to stabilize the patients agents are used as well. An association between
until liver transplantation and to optimize their pre- increase in arterial pressure and therapeutic response
transplant clinical conditions. Treatment strategies has been found. [25]
[4]
target the underlying pathophysiological mechanism
of HRS, including exerting splanchnic vasoconstriction Noradrenaline, a catecholamine with predominantly
and renal vasodilatation in combination with volume alpha-adrenergic activity, is widely available and
expansion. [12,13] Many studies have suggested that inexpensive and has been used for the treatment of
68 Hepatoma Research ¦ Volume 3 ¦ April 12, 2017