Elsevier

Journal of Hepatology

Volume 35, Issue 6, December 2001, Pages 726-732
Journal of Hepatology

Worsening of hepatic dysfunction as a consequence of repeated hydroxyethylstarch infusions

https://doi.org/10.1016/S0168-8278(01)00200-8Get rights and content

Abstract

Background/Aims: Due to its apparent safety and low cost, hydroxyethylstarch (HES) is increasingly used as a volume expander. The aim of this retrospective study was to highlight the risk of hepatic dysfunction after iterative HES infusions.

Methods: Between April 1996 and April 1998, nine patients were referred for worsening of their clinical condition after repeated HES infusions. Six patients had previous chronic liver disease, cirrhosis in four cases. All patients underwent a liver biopsy.

Results: All post-HES liver biopsies showed diffuse microvacuolization of Kupffer cells, which was associated with focal hepatocyte vacuolization in seven cases. The vacuoles contained periodic acid Schiff positive material at their margins and were lysosomal by electron microscopy. The clinical symptoms of hepatic disease, although difficult to interpret in cirrhotic patients, worsened after HES infusions. Portal hypertension was noted in three non-cirrhotic patients. Serum alkaline phosphatase and gammaglutamyl transferase activities were increased when compared with previous values. Eight patients died, six of them within 1–4 weeks of hepatic failure or septic shock. In the only living patient, symptoms improved after HES withdrawal.

Conclusions: Repeated administration of HES could favour severe portal hypertension, liver failure and sepsis, particularly in the setting of chronic liver disease. The basis of these adverse effects is the lysosomal storage of HES in Kupffer cells and hepatocytes.

Introduction

Hydroxyethylstarch (HES) is an effective colloid for intravascular volume expansion. It is extensively used in the acute treatment of shock or severe haemorrhage, but also repeatedly as a plasma expander after large volume paracentesis, haemodialysis and plasma exchanges [1]. HES is widely recognized as a good alternative to albumin because of the reduced cost and the absence of infectious risk. Adverse effects of HES are reported to be infrequent, at least after acute treatment, and to depend in part on the physicochemical characteristics of the starch. High molecular weight (MW) starch may induce coagulation disorders due to an acquired von Willebrand syndrome [2]. Cases of allergic reactions, headaches, probably due to rapid volume shifts, and peripheral oedema have also been reported [1]. With lower MW starch, the main adverse effects of HES are persistent pruritus related to HES deposition in skin histiocytes and nerves [3], [4], and impairment of immediate renal function in kidney transplant recipients [5]. HES accumulation in the liver has been occasionally reported after repetitive infusions [6], [7], [8], but little, if nothing, is known about the clinical consequences of this accumulation.

We report nine cases of patients for whom liver storage of HES after repetitive infusions was followed by worsening of hepatic dysfunction and portal hypertension.

Section snippets

Patients

Clinical and biological data are listed in Table 1. Between April 1996 and April 1998, nine patients (seven men, two women; mean age, 54 years) were referred in two hospital units (seven patients in Jean Verdier hospital and two patients in Saint-Eloi hospital) for refractory ascites (n=6; cases 1, 2, 5, 6, 8 and 9) or anicteric cholestasis (n=3; cases 3, 4 and 7) after repeated intravenous infusions of HES 6% (Elohes 6%, Fresenius France Pharma; Table 1).

Four patients had cirrhosis. Cirrhosis

Histological results

Histological results are summarized in Table 2. All post-HES liver biopsies showed diffuse microvacuolization and hyperplasia of CD68 positive Kupffer cells (Fig. 1; Table 2). The vacuoles were irregular in size; they appeared empty on H&E, were exceptionally positive for Oil-Red-O, but contained few positive granules with PAS and argentic staining of Gordon-Sweet. Hyperplasia of Kupffer cells was marked in eight cases, with a pattern of sinusoidal obstruction by clusters of foamy cells.

Discussion

HES is reputed to be a safe alternative to albumin. Our report suggests that it may not be the case in patients with chronic liver disease and for high cumulative doses of HES; the adverse effects are likely to be a direct consequence of HES tissue storage. Previous experimental studies [9], [10] and clinical reports [6], [7], [8] have shown that after massive infusions, HES accumulates in various organs, including the liver, spleen, lymph nodes, small intestine, striated muscle and skin.

Acknowledgements

The authors thank Dr Frédéric Charlotte and Dr Jean-Philippe Brouland for the supply of histological documents and to Dr Isabelle REACH for her clinical contribution.

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