Which types of graft to use in patients with acute liver failure?
(A) Auxiliary liver transplant (B) Living donor liver transplantation (C) The whole liver (A) I prefer auxiliary liver transplant
Article Outline
Abbreviations: ALF, acute liver failure, OLT, orthotopic liver transplantation, HALT, heterotopic auxiliary liver transplantation, APOLT, auxiliary partial orthotopic liver transplantation
1. Introduction
Acute liver failure (ALF) is associated with a high mortality rate [1] and the main aims of medical treatment are to avoid cerebral edema and infections, which often are responsible for patient death. Orthotopic liver transplantation (OLT) improves the 1-year survival over 60% [2], [3]. However, in selected cases ALT can be controlled by medical treatment until regeneration and recovery of the native liver may occur. For this reason, the indication for liver transplantation to treat ALT still remains controversial owing to the risk related to the operative procedure and to the lifelong need for immunosuppression. Moreover, spontaneous recovery from ALF can occur in approximately 25% of the patients with intensive medical care alone [4]. Therefore, considering the possibility that the patient’s own liver may recover, auxiliary partial liver transplantation has been developed to bridge these patients until the native liver may recover. This procedure preserves a part of the native liver leaving a chance for the liver to regenerate. When the diseased native liver is regenerated with its function fully restored, a gradual withdrawal of immunosuppressive therapy is undertaken. This strategy decreases the incidence of drug-related side effects and of monitoring requirements.
Theoretically, there are two methods to perform auxiliary liver transplantation. One is heterotopic auxiliary liver transplantation (HALT), where the graft (usually partial) is placed below the unresected native liver (Fig. 1) [5]. The other method is auxiliary partial orthotopic liver transplantation (APOLT), in which the left or the right hemiliver is resected and replaced by a partial liver graft (Fig. 2) [6]. HALT is technically easier because native hepatectomy is avoided. However, HALT requires the implantation of the graft on the infrahepatic vena cava: an area with higher caval pressure inducing a risk of venous outflow obstruction. In addition, this technique requires sufficient space in the abdomen, and there is competition for portal venous flow between the graft and the native liver. Liver regeneration after HALT may be slower than after APOLT probably due to the presence of the total remaining necrotic native liver, responsible for the release of cytokines. The results of HALT are poorer than those obtained with APOLT or total graft OLT due to an increased incidence of primary non-function and of portal vein thrombosis [7]. Some authors performed HALT with portal vein arterialization [8], [9] but the results did remain somewhat unconvincingly. Erhard et al. [8] reported four cases but only one of those patients experienced a long-term survival with his native liver. Currently, HALT is abandoned.
Fig. 1.
The auxiliary partial heterotopic liver graft (HALT) (a right reduced liver) is implanted below the native liver.
Fig. 2.
The auxiliary partial orthotopic liver graft (APOLT) is reduced to a left or right liver before being implanted orthotopically after the left (a) or the right (b) native liver has been removed (c) technique of hepato-caval anastomosis.
Our own experience: Our team reported one case in 1993 [10], a series of eight patients who underwent APOLT for fulminant and subfulminant hepatic failure in 1995 [11], and a larger series in 2002 [12]. Altogether, we have performed 16 APOLT in 15 patients with ALF. The cause of liver failure was viral (HAV: n
=3; HBV: n=3), drugs (n=4), or others (n=5). A right hemiliver was used in 10 patients, and a left hemiliver in 6. Ten were adults and 5 children. After APOLT encephalopathy and cerebral edema improved in 13 patients who could be extubated within 2 weeks after grafting. Two patients required re-transplantation: one for primary non-function treated by OLT and one for hepatic vein thrombosis treated by re-APOLT. Ten patients (66.7%) are alive. The remaining five patients died 1–6 months after transplantation as they suffered from infectious complications in four cases and from a massive pulmonary embolism in one case. Regeneration of the native liver occurred in 11 of the 15 patients (73.3%) and in eight of the 10 survivors (80%). In six of these eight patients the immunosuppressive therapy could be discontinued permanently.
2. Results in the literature
Several other centers observed the same favorable outcome. The long-term outcome after auxiliary liver transplantation is summarized in Table 1. Some series are heterogeneous, including both APOLT and HALT [7], [13]. In the EURALT study group [7], the results following APOLT were better with a one-year survival rate of 71% (25/35). Of these patients, 12 were free of immunosuppression or with the graft removed. Kasahara et al. [18] reported a large series of 31 patients with poor results. Surprisingly, in no patient discontinuation of immunosuppression could be achieved. In this series indications for APOLT were heterogeneous, with only six patients undergoing APOLT for acute liver failure. Moreover, analysis of the APOLT’s technical aspects shows that portal vein diversion was used in 83% of their study patients in order to avoid functional portal flow competition.
Table 1. Results after auxiliary liver transplantation in a literature
| Number of patients | Alive | Alive without immunosuppression or with graft removed | Retransplantation | Follow-up (years) | |
|---|---|---|---|---|---|
| Chenard-Neu et al. 1996 [13] | |||||
| APOLT | 24 | 16 | 13 | 3 | 1.5 |
| HALT | 6 | 3 | |||
| Sudan et al. 1997 [14] | 7 | 4 | 4 | 1 | 3.5 |
| Pereira et al. 1997 [15] | 7 | 3 | 2 | 0 | 1 |
| Van Hock et al. 1999 [7] | |||||
| APOLT | 35 | 25 | 12 | 4 | 1 |
| HALT | 12 | 4 | 4 | 3 | 1 |
| OLT | 384 | 232 | – | – | 1 |
| Azoulay et al. 2001 [16] | |||||
| APOLT | 12 | 8 | 2 | 3 | 1 |
| OLT | 24 | 18 | – | 0 | 1 |
| Boudjema et al. 2002 [17] | 17 | 11 | 6 | 3 | 4.5 |
| Kasahara et al. 2005 [18] | 31 | 18 | – | 5 | – |
Azoulay et al. [16] compared the results of APOLT with those of conventional OLT for the treatment of ALT. They showed similar survival rates after both procedures, but the postoperative complication rates (particularly biliary complications and neurological sequelae as well as the retransplantation rate) were significantly higher after APOLT. This latter study presented a small group of patients, and is the only series showing an inferior neurological outcome. Moreover, neurological sequelae have been also observed after OLT by the same team [3], [19]. Indeed, there are two major conditions to avoid neurological sequelae: better selection of the patients for APOLT and above all, an adequate timing of transplantation.
3. Remaining controversies
There are still several unresolved problems in the clinical application of APOLT. The main concern of many authors is the functional competition resulting from the portal blood flow shared between the graft and the native liver. To overcome this problem and to optimize flow to the graft, some authors have banded or even ligated the native liver’s portal vein [18]. This procedure could lead to dysfunction and damage to the native liver compromising repair mechanisms such as regeneration. Additionally, the absence of portal flow is known to result in liver fibrosis, or even cirrhosis. Other authors have proposed the ligation of the middle hepatic vein [20]. The problem is quite different between APOLT for acute liver failure and for non-cirrhotic metabolic liver diseases. In non-cirrhotic metabolic liver diseases in which the parenchyma is structurally normal, the intrahepatic liver resistance in the native liver is not increased. In contrast, in case of acute liver failure, during the early postoperative period the native liver has a high resistance and most of the portal blood flow is shifted into the graft. Later on, when the native liver has recovered and intrahepatic resistance is normalized, an opposite effect may occur, leading to decreased portal blood supply to the graft. This phenomenon might be responsible for partial graft atrophy. Fortunately, at this time the patient is no longer dependent on a functioning graft. Interestingly, Lee SG et al. [21] reported a series of 130 patients of adult-to-adult living donor liver transplantation using dual grafts (2 hemilivers from two different donors) (see article by Lee in this Forum). In their experience functional portal flow competition between both non-identical grafts was not observed. These results are not in favor of a functional portal flow competition between both livers. If portal inflow to the graft is decreased, some authors recommend step-by-step percutaneous embolization of the branches of the native right lateral portal vein with careful follow-up studies of the liver function [22]. In contrast, excessive portal blood flow entering into a small graft results in rapid deterioration, leading to dysfunction and recipient death in some cases [23]. In our experience, portal blood flow competition was not observed. Portal vein diversion was never performed, as it seems to carry more risks than advantages [24]. There are no definitive rules to indicate which type of reduced auxiliary graft should be implanted. However, a right APOLT seems more suitable, since the right liver provides more functional parenchyma to restore liver function rapidly. Right APOLT seems mandatory for adult recipients. Left APOLT harvested from an adult appears sufficient for children. The same rules applied to living donor liver transplantation may be used for APOLT.
Other concerns include deleterious effects of the necrotic liver on the graft function [25] and the difficulty in predicting regeneration of the remnant native liver before the transplantation. APOLT should only be proposed to patients with high chances of liver regeneration such as age <40 years, with fulminant rather than subfulminant hepatitis, and due to virus A, B or to paracetamol [13]. Preoperative fresh frozen biopsy of the native liver could not show reliable prognostic factors of regeneration. Surviving hepatocytes, even if few in number but if relatively damage-free, have the potential for extensive regeneration with the potential for complete recovery of the native liver [13], [15]. However, theoretically, all patients with ALF who meet the criteria for transplantation could undergo APOLT. Indeed, even if the native liver does not regenerate, the auxiliary graft should function as a normal liver graft. In contrast, if the liver regenerates, the need for lifelong immunosuppression is obviated.
Finally, APOLT still has a high morbidity which may be related to a learning curve effect. With the experience from living donor liver transplantation, a decrease of the morbidity and mortality rate after APOLT can be expected.
In conclusion, APOLT is an effective procedure for avoiding life-threatening cerebral edema in patients with ALF. It is the only procedure which enables to gain sufficient time to let the native liver regenerate, and importantly, which may allow to stop at a stage the immunosuppressive therapy. APOLT should be preferred to HALT. Portal vein diversion is not necessary. APOLT should definitely be considered as a valid therapeutic option, as it sustains liver function temporarily, gives the native liver a chance to recover, and subsequently avoids lifelong immunosuppression. The graft volume should be carefully evaluated in order to avoid graft insufficiency (small-for-size syndrome). When the native liver has regenerated it is recommended to reduce gradually immunosuppression inducing a progressive atrophy of the graft which is left with the patient. Removal of the auxiliary graft should not be attempted.
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PII: S0168-8278(07)00053-0
doi:10.1016/j.jhep.2007.01.012
© 2007 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
