LIVER TRANSPLANTATION 13:1614-1615, 2007
LETTER TO THE EDITORS
Pretransplant Albumin Dialysis in Erythropoietic Protoporphyria: A Costly Detour Received June 7, 2007; accepted June 10, 2007.
TO THE EDITORS: We read with great interest the recent article by Eefsen et al.,1 which describes the latest of more than 40 cases of liver transplantation in erythropoietic protoporphyria (EPP) that have been done to date.2 To optimize for liver transplantation, albumin dialysis was used to reduce the amount of circulating protoporphyrin IX (PPIX). The erythrocyte protoporphyrin IX (Erc-PPIX) concentration was studied before and after albumin dialysis and compared to plasmapheresis, which fell short by comparison. Albumin dialysis has never previously been described in EPP, and thus this report is of great interest. Unfortunately, we still do not know what the effects are. At least 80% of protoporphyrin originates from bone marrow3 and enters circulation in red blood cells, where it diffuses across the red cell membrane and binds to albumin, hemopexin, and lipoproteins, predominantly low-density lipoprotein (LDL).4 Because of pronounced hydrophobicity, PPIX is not present as an active monomer in an aqueous solution. Albumin dialysis removes water-soluble and albumin-bound substances.5 In EPP, the treatment target is subsequently to reduce the circulating amount of PPIX bound to albumin. The intra-erythrocyte concentration of PPIX is at least 10 times higher than that of plasma,6 but hepatic uptake is mainly from the plasma compartment.7 Transfer in both directions between erythrocytes and plasma takes place,6 and an individual balance between compartments has been described8 that is influenced by conditions related to EPP liver disease.9 To reduce the burden of circulating PPIX for a liver already injured by the PPIX load in EPP, several methods have been described. Marrow production can be reduced via feedback inhibition by erythrocyte hypertransfusion, and circulating amounts of PPIX can be reduced by plasmapheresis or erythrocyte apheresis (see the references in Wahlin et al.9). Lipoprotein apheresis, such as LDL apheresis, is also an alternative to consider but has not been described before. In a recent case of EPP liver failure in our own cen-
ter,9 we employed erythrocyte hypertransfusion, plasmapheresis, erythrocyte apheresis, and LDL apheresis to reduce the PPIX burden on the liver. Giving 6 units of erythrocytes over 3 days reduced the Erc-PPIX concentration by 46%, probably because of dilution, whereas the plasma protoporphyrin IX (P-PPIX) concentration decreased by 10%, probably reflecting absorption by transfused erythrocytes. Three plasmaphereses over 7 days caused a 40% reduction in P-PPIX and a 6% reduction in Erc-PPIX. Erythrocyte apheresis replacing one-half of the erythrocyte mass led to a 51% reduction in Erc-PPIX and an 11% reduction in P-PPIX. LDL apheresis led to a 53% reduction in the plasma LDL concentration and a 25% reduction of P-PPIX, and this reflected the major importance of LDL as a plasma protoporphyrin carrier. Eefsen et al.1 show a 5.9%-9.1% reduction of ErcPPIX with 2 different methods of extracorporeal albumin dialysis versus a 0.8% reduction by plasmapheresis. Unfortunately, the effects on P-PPIX were not investigated. If the main treatment effect is reduction of plasma concentration, measuring the erythrocyte concentration is plausibly studying a slow secondary effect to changes in the plasma compartment. Whether the reduction in Erc-PPIX reflects a reduction in P-PPIX or rather an increase in the binding capacity of albumin after removal of other albumin-bound substances is not known. The possible presence or concentration of protoporphyrin in the dialysate was not investigated. Both effects and costs are interesting when methods for reduction of circulating protoporphyrin in EPP are compared. Although erythrocyte hypertransfusion reduces production, erythrocyte apheresis removes the most substantial total amount of protoporphyrin, and plasmapheresis and LDL apheresis produce the quickest reduction in the amount of protoporphyrin that is immediately available for hepatic uptake. Average costs of different procedures in our own institution are shown in Table 1. The molecular adsorbent recirculating system, the method for extracorporeal albumin regenerating liver support that we use, is considerably more costly than the other methods. Acute-on-chronic liver failure, such as the EPP case
Address reprint requests to Staffan Wahlin, Karolinska University Hospital, Huddinge K63, Stockholm 141 86, Sweden. Telephone: ⫹46858587984; FAX: ⫹46858582335; E-mail:
[email protected] DOI 10.1002/lt.21259 Published online in Wiley InterScience (www.interscience.wiley.com).
© 2007 American Association for the Study of Liver Diseases.
LETTER TO THE EDITORS 1615
TABLE 1. Mechanisms and Effects Associated with Different Procedures To Reduce Circulating Protoporphyrin in Erythropoietic Protoporphyria Cost per Procedure Patient in Wahlin et al.9 Erc transfusion (6 units) Erc apheresis
Mechanism
Effects
US Dollars
Euros
Reduction of PPIX production
Erc-PPIX: ⫺46% P-PPIX: ⫺10% Erc-PPIX: ⫺51% P-PPIX: ⫺11% P-PPIX: ⫺40%† Erc-PPIX: ⫺6% P-LDL: ⫺53% P-PPIX: ⫺25%
900
700*
2600
2000
1600
1200
1400
1100
7100
5500
Reduction of Erc-PPXI
Plasmapheresis
Reduction of P-PPIX
LDL apheresis
Reduction of P-PPIX
Patient in Eefsen et al.1 MARS
Reduction of P-PPIX ?
P-PPIX: unknown Erc-PPIX: ⫺9.1%
NOTE: Average costs are stated as debited within Karolinska University Hospital (overhead costs are not included). Abbreviations: Erc, erythrocyte; Erc-PPIX, erythrocyte protoporphyrin IX; LDL, low-density lipoprotein; MARS, molecular adsorbent recirculating system; P-LDL, plasma low-density lipoprotein; P-PPIX, plasma protoporphyrin IX; PPIX, protoporphyrin IX. *Six Erc units. † Three procedures in 7 days.
that Eefsen et al.1 describe, is an accepted indication for albumin dialysis. However, Eefsen et al. fail to show any effect on P-PPIX and only a marginal effect on ErcPPIX. Whether albumin dialysis should be considered a treatment option to alleviate the protoporphyrin burden in EPP liver failure or merely a costly detour is unfortunately still not clear. Staffan Wahlin1 Pauline Harper2 1 Department of Gastroenterology and Hepatology Karolinska University Hospital Stockholm, Sweden 2 Porphyria Centre Sweden Karolinska University Hospital Stockholm, Sweden
REFERENCES 1. Eefsen M, Rasmussen A, Wulf HC, Brock A, Hansen BA. Erythropoietic protoporphyria and pretransplantation treatment with nonbiological liver assist devices. Liver Transpl 2007;13:655-657. 2. Anstey AV, Hift RJ. Liver disease in erythropoietic proto-
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LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
