Treatment of Split-Liver Recipients with Poor Graft Function by Albumin-Dialysis (Mars)

In the face of donor shortage, split-liver transplantation plays an increasing role in organ supply for patients in terminal chronic liver disease. However, occasionally grafts may be small for size or function uptake is delayed. In these critical situations, liver support is warranted to compensate for the not yet adequate graft function. A new treatment based dialysis against an albumin-containing dialysate (Molecular Adsorbents Recirculating System, MARS) was developed to selectively remove albumin-bound and water-soluble endogenous toxins from the patients, while plasma proteins themselves and substances bound to proteins other than albumin remain in the blood [1] [2]. The albumin solution is cleaned on-line by charcoal and resin perfusion, water-soluble substances are cleared by an integrated low-flux dialysis. Previously, beneficial effects of this treatment have been reported in acute-on-chronic hepatic failure as well as in hepatorenal syndrome [3] [4] [5].

We report on four split-liver recipients with poor graft function in the early postoperative phase who were treated with MARS at a total of 10 single treatments (Table 1).

Table 1 Split-liver recipients with postoperative dysfunction of the grafted organ, that received MARS treatments Nr. Patient Initials Gender, Age Main diagnosis Concomitant kidney failure 1 C.J. Female, 43 Liver metastases, primary tumor resected + 2 G.A. Male, 60 Chronic hepatitis B and hepato-cellular Ca. + 3 Z.M. Female, 41 Cryptogenic liver cirrhosis + 4 G.M. Male, 62 Chronic hepatitis C +

Dialysis duration was 4,5-6 hours daily. Each treatment resulted in a substantial reduction of serum bilirubin levels. The average decrease for total bilirubin was 29,5 %, for direct bilirubin 38,3 %. Average pre-treatment levels were 30,5 (range 16,6-59,0) and 22,7 (range 12,1-45,6) mg/dl, respectively. Consecutive treatments were accompanied by an increased degree of alertness as well as by improved subjective well-being of the patients. Adverse effects were not observed. One patient was listed for high-urgency re-transplantation at the same time of MARS initiation and was transplanted the following day. Graft function of the other three improved during the treatment phase, as shown in a spontaneous further decline or stabilization of serum bilirubin levels at markedly lower values after discontinuation of MARS (Fig. 1). This was accompanied by an ongoing improvement of clinical status of the patients. However, patient #2 after being transferred to peripheral surgical ward service developed a severe pneumonia one week after MARS treatment was halted and later died in septic multi-organ failure. The other three patients survived and could be discharged from the hospital in good clinical condition.

In conclusion, albumin-dialysis (MARS) may be an additional therapeutic means in the support of split-liver recipients in the early postoperative phase. Diminishing the toxic load of the patients may be favourable for liver regeneration and improvement of graft function. However, more cases are needed for a deeper evaluation of both the potential and safety of this new treatment modality.

Fig. 1 Course of serum bilirubin concentration [mg/dl] in patient # 2. MARS treatment was started as an additional therapeutic means due to progressive decline of graft function with severe cholestasis and kidney failure. After three single treatments of approximately 5 hours duration each, serum bilirubin level stabilized at values about 50 % lower than at the time of start of treatment.

Reference

• 1 Stange J, Ramlow W, Mitzner S, Schmidt R, Klinkmann H. Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins.  Artif. Org. 1993;  17 809-813
• 2 Stange J, Mitzner S, Ramlow W, Gliesche H, Hickstein H, Schmidt R. A new procedure for the removal of protein bound drugs and toxins.  ASAIO J. (1993);  39 M621-M625
• 3 Stange J, Mitzner S R, Risler T, Erley C M, Lauchart W, Goehl H, Klammt S, Peszynski P, Freytag J, Hickstein H, Löhr M, Liebe S, Schareck W, Hopt U T, Schmidt R. Molecular Adsorbent Recirculating System (MARS): Clinical results of a new membrane-based blood purification system for bioartificial liver support.  Artificial Organs. (1999);  23 319-330
• 4 Mitzner S, Stange J, Klammt S, Risler T, Erley C M, Bader B M, Berger E D, Lauchardt W, Peszynski P, Freytag J, Hickstein H, Loock J, Löhr J M, Liebe S, Emmrich J, Korten G, Schmidt R. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.  Liver Transplantation. (2000);  6 277-286
• 5 Stange J, Mitzner S R, Klammt S, Freytag J, Peszynski P, Loock J, Hickstein H, Korten G, Schmidt R, Hentschel J, Schulz M, Lohr M, Liebe S, Schareck W, Hopt U T. Liver support by extracorporeal blood purification: a clinical observation.  Liver Transplantation. (2000);  6 603-613