Chin Med J 2011;124(10):1458-1464
Alternatives to albumin administration in hepatocellular
carcinoma patients undergoing hepatectomy: an open,
randomized clinical trial of efficacy and safety
YANG Jian, WANG Wen-tao, YAN Lü-nan, XU Ming-qing and YANG Jia-yin
Keywords: artificial colloids; hepatectomy; hepatocellular carcinoma; inflammatory response; volume replacement
Background The value of artificial colloids in treating patients with liver disease is controversial. The effects of
intravascular volume replacement regimens on liver function secondary to alteration of the postoperative inflammatory
response are not known. In this study, we evaluated the effects of different volume replacement regimens in
hepatocellular carcinoma patients undergoing hepatectomy to clarify whether albumin administration can be replaced by
other volume replacement products.
Methods Ninety consecutive hepatocellular carcinoma patients scheduled for hepatectomy were prospectively
randomized to receive 20% human albumin (HA), 6% hydroxyethyl starch (HES) or lactated Ringer’s solution (LR) for
postoperative volume replacement. Hemodynamic, liver function and inflammatory response parameters were recorded
on postoperative days one, three, and five throughout the investigation period.
Results Significantly less volume was required in the HA and the HES groups. Although patients in all groups had
similar baseline values, the plasma osmolality was significantly higher in the HA and HES groups. Total bilirubin (TB),
alanine aminotransferase (ALT), and aspartate aminotransferase (AST) increased from baseline in all groups, and did not
differ significantly between groups. C-reactive protein (CRP) was significantly lower in the HES group compared with the
Conclusions In hepatocellular carcinoma patients undergoing hepatectomy, HA can be replaced by HES or LR in well
selected patients. Hemodynamic stability, liver function, and postoperative clinical outcomes could be equivalently
achieved in the HES group; also, HES may exert more favorable effects on the acute phase response. (Registered in the
Chinese Clinical Trial Registry, ChiCTR-TRC-10000790)
Chin Med J 2011;124(10):1458-1464
emodynamic stability is a prerequisite for adequate
tissue perfusion and energy metabolism and is
essential in the management of patients undergoing major
surgery. Different intravascular volume replacement
regimens have been proposed for volume replacement
therapy. A novel 6% hydroxyethyl starch (HES) with an
intermediate molecular weight (MW, 130 000 Dalton)
and a very low degree of substitution (Ds 0.4) (HES
130/0.4; Voluven®, Fresenius AG, Bad Homburg,
Germany) has been approved in several countries for
routine volume replacement. HES 130/0.4 has been
reported to have significant pharmacokinetic and
pharmacodynamic advantages such as a stable volume
effect, decreased tissue storage, rapid plasma elimination
and a low impact on coagulation.1,2 In addition to the
effect on maintenance and stability of hemodynamic
parameters, some studies in vitro and in vivo have shown
that HES may even exert anti-inflammatory effects.3,4
The effects may result in less endothelial cell damage and
an improved microcirculation.
In patients undergoing major hepatic resection,
intravascular volume depletion is often seen after surgery
for several reasons. The consequence of hypovolemia is
the inexorable development of complex pathophysio-
logical processes including progressive liver failure,
which is a major contributor to postoperative mortality.
Following liver resection, the disturbance of the balance
between immediate and ongoing loss of hepatocytes and
liver regeneration explains the nature of evolving liver
failure. We know that in liver resection, inflow occlusion
and subsequent restoration of blood supply causes
reperfusion injury, termed ischemia-reperfusion injury
(IRI). This can lead to ongoing loss of hepatocytes and
postoperative liver insufficiency, particularly in patients
with cirrhosis. However, the remnant liver has a strong
ability to regenerate after partial hepatectomy. It is well
known that some inflammatory mediators are important
in the mechanisms of both IRI and liver regeneration.
During liver resection, the liver is exposed to variable
Division of Liver Transplantation, West China Hospital, West
China Medical School of Sichuan University, Chengdu, Sichuan
610041, China (Yang J, Wang WT, Yan LN, Xu MQ and Yang JY)
Correspondence to: Dr. WANG Wen-tao, Division of Liver
Transplantation, West China Hospital, West China School of
Medicine, Sichuan University, Chengdu, Sichuan 610041, China
(Tel: 86-28-85422476. Fax:
This work was supported by a grant from the National Science and
Technology Major Project of China (No. 2008ZX10002-025).
Chin Med J 2011;124(10):1458-1464
LR groups. Patients in the HES and LR groups
experienced more severe hypoalbuminemia compared
with those in the HA group. However, compared to HA,
infusion of HES had equivalent outcomes in terms of
hemodynamic stability, liver function and postoperative
clinical outcomes. In addition, HES may exert more
favorable effects on the acute phase response. Therefore,
we conclude that in patients with hepatocellular
carcinoma undergoing hepatic resection, when the serum
albumin concentration is >25 g/L, HA cannot be routinely
used, can be replaced by HES or LR.
Acknowledgments: We thank Dr. SHAO Zheng-yong for his
technical assistance and CHEN Pei-xian for her assistance in
Wu Y, Wu AS, Wang J, Tian M, Jia XY, Rui Y, et al. Effects of
the novel 6% hydroxyethyl starch 130/0.4 on renal function of
recipients in living-related kidney transplantation. Chin Med J
2010; 123: 3079-3083.
Felfernig M, Franz A, Braunlich P, Fohringer C,
Kozek-Langenecker SA. The effects of hydroxyethyl starch
solutions on thromboelastography in preoperative male
patients. Acta Anaesthesiol Scand 2003; 47: 70-73.
Feng X, Liu J, Yu M, Zhu S, Xu J. Protective roles of
hydroxyethyl starch 130/0.4 in intestinal inflammatory
response and survival in rats challenged with polymicrobial
sepsis. Clin Chim Acta 2007; 376: 60-67.
Wang P, Li Y, Li J. Protective roles of hydroxyethyl starch
130/0.4 in intestinal inflammatory response and oxidative
stress after hemorrhagic shock and resuscitation in rats.
Inflammation 2009; 32: 71-82.
Wang H, Li ZY, Wu HS, Wang Y, Jiang CF, Zheng QC, et al.
4/nuclear factor-kappa B pathway. Chin Med J 2007; 120:
Shirasugi N, Wakabayashi G, Shimazu M, Oshima A, Shito M,
Kawachi S, et al. Up-regulation of oxygen-derived free
radicals by interleukin-1 in hepatic ischemia/reperfusion injury.
Transplantation 1997; 64: 1398-1403.
Zhai ST, Liu GY, Xue F, Sun GP, Liang L, Chen W, et al.
Changes of sphingolipids profiles after ischemia-reperfusion
injury in the rat liver. Chin Med J 2009; 122: 3025-3031.
Webber EM, Bruix J, Pierce RH, Fausto N. Tumor necrosis
factor primes hepatocytes for DNA replication in the rat.
Hepatology 1998; 28: 1226-1234.
Iwai M, Cui TX, Kitamura H, Saito M, Shimazu T. Increased
secretion of tumour necrosis factor and interleukin 6 from
isolated, perfused liver of rats after partial hepatectomy.
Cytokine 2001; 13: 60-64.
10. Tiberio GA, Tiberio L, Benetti A, Cervi E, Montani N, Dreano
M, et al. IL-6 Promotes compensatory liver regeneration in
cirrhotic rat after partial hepatectomy. Cytokine 2008; 42:
11. Menger MD, Vollmar B. Surgical trauma: hyperinflammation
versus immunosuppression? Langenbecks Arch Surg 2004;
12. Christidis C, Mal F, Ramos J, Senejoux A, Callard P, Navarro
R, et al. Worsening of hepatic dysfunction as a consequence of
repeated hydroxyethylstarch infusions. J Hepatol 2001; 35:
13. Du B, Pan J, Chen D, Li Y. Serum procalcitonin and
interleukin-6 levels may help to differentiate systemic
inflammatory response of infectious and non-infectious origin.
Chin Med J 2003; 116: 538-542.
14. Li AM, Quan Y, Guo YP, Li WZ, Cui XG. Effects of
therapeutic hypercapnia on inflammation and apoptosis after
hepatic ischemia-reperfusion injury in rats. Chin Med J 2010;
15. Lang JD, Jr., Figueroa M, Chumley P, Aslan M, Hurt J, Tarpey
MM, et al. Albumin and hydroxyethyl starch modulate
oxidative inflammatory injury to vascular endothelium.
Anesthesiology 2004; 100: 51-58.
16. Wiedermann CJ. Colloidal and pharmacological activity of
albumin in clinical fluid management: recent developments.
Curr Drug Ther 2006; 1: 319-328.
17. Xie J, Lv R, Yu L, Huang W. Hydroxyethyl starch 130/0.4
exerts its anti-inflammatory effect in endotoxemic rats by
inhibiting the TLR4/NF-kappaB signaling pathway. Ann Clin
Lab Sci 2010; 40: 240-246.
18. Tsuchihashi S, Tamaki T, Tanaka M, Kawamura A, Kaizu T,
Ikeda A, et al. Pyrrolidine dithiocarbamate provides protection
against hypothermic preservation and transplantation injury in
the rat liver: the role of heme oxygenase-1. Surgery 2003; 133:
19. Kim YI, Song KE, Ryeon HK, Hwang YJ, Yun YK, Lee JW, et
al. Enhanced inflammatory
Hepatogastroenterology 2002; 49: 1077-1082.
20. Dierssen U, Beraza N, Lutz HH, Liedtke C, Ernst M,
Wasmuth HE, et al. Molecular dissection of gp130-dependent
pathways in hepatocytes during liver regeneration. J Biol
Chem 2008; 283: 9886-9895.
21. Kunduzova OR, Bianchi P, Pizzinat N, Escourrou G, Seguelas
MH, Parini A, et al. Regulation of JNK/ERK activation, cell
apoptosis, and tissue regeneration by monoamine oxidases
after renal ischemia-reperfusion. FASEB J 2002; 16:
22. Haynes GR, Navickis RJ,
administration--what is the evidence of clinical benefit? A
systematic review of randomized controlled trials. Eur J
Anaesthesiol 2003; 20: 771-793.
Wilkes MM. Albumin
(Received November 22, 2010)
Edited by HAO Xiu-yuan