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There are currently several techniques available for liver transplantation, some of which apply only to patients with FHF. Generally, liver transplantation in this group of patients can be done with an orthotopic or a heterotopic approach. Orthotopic liver transplantation involves a total hepatectomy followed by placement of an allograft in the anatomic position. In heterotopic liver transplantation (HLT), the native liver is left intact and the liver allograft is placed in a nonanatomic position. Orthotopic liver transplantation has several advantages that include removal of a necrotic liver, adequate space for placing the new liver, ease of anatomic alignment, a single organ to assess for function and use of commonly applied transplantation techniques. The standard techniques of orthotopic liver transplantation, developed by Starzl and his associates and modified by others, are well described in the surgical literature and will not be further elaborated in this chapter.48-51 There are, however, several negative aspects of OLT relative to HLT in the setting of FHF. They include greater risk of bleeding during the hepatectomy phase because many of these patients have profound coagulopathy, removal of an organ which (if not completely necrotic) may regenerate and become functional again, need for life-long immunosuppression and increased risk of developing malignancies. Despite these potential disadvantages, OLT still is the most commonly used approach for transplanting FHF patients.

In the classic orthotopic approach, the infra- and supra-hepatic vena cava are clamped, the patient is placed on portosystemic veno-venous bypass and the retro-hepatic IVC is excised with the liver.52 Initially, veno-venous bypass was thought to be essential for maintaining hemodynamic stability during the anhepatic phase; however, several studies have shown the feasibility of OLT without veno-venous bypass.52,53 Using the so-called "piggyback" technique, total hepatectomy is completed with preservation of the retro-hepatic IVC, thus obviating the need for clamping the IVC.10,54,55 The donor supra-hepatic IVC is sewn to a caval cuff fashioned by the tributaries of the left, middle and possibly right hepatic veins, while the infra-hepatic IVC stump is oversewn (Fig. 6.1). The advantage of this procedure is to avoid the hemodynamic changes associated with clamping the IVC and veno-venous bypass; in addition, it involves only a single caval anastomosis. This technique

Veno Venous Bypass Liver Transplant
Fig. 6.1. Orthotopic liver transplantation using the "piggy back" technique. 1. Total hepatectomy with preservation of the retrohepatic IVC; 2. Implantation of the allograft with a single suprahe-patic caval anastomosis. Notice that the donor infrahepatic IVC stump has been oversewn.

has been used for patients with FHF; however, it is not performed routinely in this setting due to technical considerations.

The results of liver transplantation for patients with FHF using the classic technique have been variable. Ascher et al reported 1 year actuarial survival rates of 92% and 100% in 35 patients with FHF and SFHF respectively.10 On the other hand, Bismuth et al reported a 68% 1 year survival following OLT in 116 patients with FHF.20 The primary reason for this difference in survival is the difference in patient selection criteria among various centers. Exclusion of high-risk patients (patients with high ICP and low CPP) improves OLT survival. A more meaningful comparison of center-specific survival data can be carried out if the survival of the total number of FHF patients treated at a center is reported, not just survival of patients undergoing OLT.

HLT was first attempted in the laboratory by Welch and coworkers in 19 5 5.56 More recently, the procedure was popularized by Terpstra.57,58 In HLT, the allograft is placed in the right paravertebral gutter after mobilizing the right colon and the hepatic flexure medially. Vascular anastomoses are performed in a nonanatomic fashion in contrast to the orthoto-pic procedure, commonly using an end to side configuration. The supra-hepatic IVC of the donor is anastomosed in an end to side fashion to the recipient's infra-renal vena cava, while the donor infra-hepatic vena cava is oversewn. The donor portal vein is anastomosed to the recipient's portal vein in an end to side fashion. The donor hepatic artery with a Carrel patch of the aorta is sutured to the recipient's infrarenal aorta. Finally, biliary reconstruction is completed with a Roux-en-Y hepatico-jejunostomy. The alignment of the native blood vessels and bile duct is not disturbed. A major disadvantage of HLT is the lack of adequate space in the abdominal cavity; thus, selection of either small or reduced size grafts may be necessary. Unlike patients with chronic liver disease, long standing tense ascites does not usually occur in FHF and the abdominal wall is usually not stretched. If the graft is too large, abdominal closure may be difficult and may result in compression of the venous structures, or it can cause respiratory failure and need for prolonged intubation.

According to Shaw, auxiliary HLT is an ideal treatment for FHF if the following criteria are met:

1. Recovery of the native liver is a certainty;

2. The allograft fits into an adequate heterotopic position;

3. The venous outflow and portal venous inflow to the graft are satisfactory for the duration of required support.59

Moritz was the first to report successful use of HLT in a 19-year-old woman with non-A, non-B, non-C hepatitis with FHF and stage IV hepatic encephalopathy; the patient recovered fully. He and his associates chose the heterotopic position, citing an adverse effect of manipulation of the necrotic liver on ICP, causing severe hemodynamic instability. Despite the use of a reduced size donor liver, which was placed in the right paravertebral gutter, abdominal wound closure required a silastic mesh. The surgeons reported that native liver biopsy at 6 months showed cirrhosis; however, subsequent evaluation at 22 months revealed normal native liver histology and absent hepatocytes with diffuse fibrovascular (granulation) tissue in the graft. Imaging studies revealed a shrunken graft with no hepato-cyte function and a native liver of normal size and function. Immunosuppression was withdrawn and the graft allowed to undergo atrophy. At 44 months following HLT, the patient continued to have normal life and normal liver function.61 Several other cases have been described since the initial report; however, the experience with HLT remains limited.62-64 Most of the reported graft failure in HLT is due to technical reasons, primarily inadequate portal venous flow due to portal "steal", with preferential blood flow into the native portal vein or compression of either the portal vein or IVC due to inadequate space. At this time, there have been no reports of removal of the native liver and long-term survival with an allograft in the heterotopic position.

Auxiliary, partial, orthotopic liver transplantation (APOLT) was developed as a result of the increasing interest in "bridging" patients until the native liver regenerates. The ortho-topic position has two advantages over the heterotopic position. First, the graft hepatic vein can be implanted into an anatomic position and provide better venous drainage of the liver. Second, it reduces the volume of both native and donor livers, thus facilitating abdominal closure. Tight abdominal closure jeopardizes portal flow into the native liver by increasing parenchymal resistance, already elevated due to massive necrosis; and, subsequently, it affects the ability of the native liver to regenerate. Boudjema reported the first series of APOLT in FHF and SFHF. The procedure includes:

1. Partial native liver resection (left lateral segment, left lobe, or right lobe);

2. Back-table segmental resection (Couinaud's classification) of the donor liver;

3. Implantation of the reduced size graft into its orthotopic position beside the remaining native liver (Fig. 6.2).

Four of 8 patients (50%) demonstrated complete regeneration of the native liver within 4 months, immunosuppression was discontinued and the allograft was surgically removed.65 Similar results were reported by the European multicenter study summarizing the experience with 30 patients who underwent APOLT for FHF.63 After a median follow-up of 11 months (range 3-67 mo), 63% of the patients were alive and 13 (43%) recovered normal native liver function. The percentage and distribution of necrosis observed on intraoperative biopsy of the native liver were not related to the final outcome. More important factors were the age of a patient and underlying disease etiology. Bismuth et al reported complete native liver regeneration in 3 of 5 patients who underwent AOPLT for FHF secondary to Reye's syndrome, HAV and HBV.66 All 3 patients were under the age of 40 years. Additional experience

Liver Vena Cava
Fig. 6.2. Auxiliary partial orthotopic liver transplant (APOLT). Left hepatic allograft is implanted in the orthotopic position following a recipient left hepatic lobectomy. Both the vena cava and portal vein are kept in their anatomic position with end to end anastomosis to the recipient vessels.

with AOPLT was reported recently by Shaw et al showing native liver regeneration in 6 of 7 patients with severe liver injury and hepatocyte necrosis between 50-100%.67 Three patients were alive with a nonfunctioning allograft after withdrawal of immunosuppression, while in the remaining four the grafts had to be surgically removed.

Living related liver transplantation (LRLT), either auxiliary or total, has become an accepted surgical modality for treatment of children with chronic liver disease due to the shortage of pediatric organ donors; however, only a few cases have been reported in the setting of FHF.68-70 The critical issue in LRLT is the adequacy of the size of the graft harvested from the donor. Extensive donor hepatectomy may jeopardize donor safety, while a small graft may be inadequate to handle the metabolic needs of the recipient. The use of a right lobe provides a larger graft; however, harvesting a right lobe for LRLT is technically more difficult and can result in increased operative morbidity and mortality. The left lateral segment, or left lobe, is the preferred graft to use and the donor operation is safer.71 The minimal effective graft size remains unknown; however, limited data from the LRLT experience suggest that a minimum graft weight to recipient body weight ratio of 0.5-1.9%, or a graft volume to recipient estimated liver volume ratio of 25%, is necessary for immediate graft function.69,72,73

With the increasing shortage of organ donors, few patients with FHF may develop a "toxic liver syndrome" characterized by severe intracranial hypertension, profound lactic acidosis, hemodynamic instability and multisystem organ failure. Ringe et al reported their experience in patients with primary allograft nonfunction who experienced immediate reversal of refractory shock following allograft removal.74 This observation was supported by Husberg, who reported three patients with FHF and severe lactic acidosis which was corrected by hepatic devascularization.75 These and other clinical observations led to the suggestion that removal of the necrotic liver may result in improved hemodynamic status and a decrease in ICP. In such extreme cases, a two-stage procedure is applied: total hepate-ctomy with end to side portocaval shunt followed by liver transplantation when an allograft becomes available. The largest series of patients with FHF rendered anhepatic while awaiting liver transplantation was recently reported by Ringe et al.76 Thirty-two adults with "toxic liver syndrome" underwent total hepatectomy and portocaval shunt. Thirteen patients did not show any signs of improvement after hepatectomy and died rapidly from multisystem organ failure, while 19 became more stable and underwent the full procedure. Patients were anhepatic for 987 ± 433 min (range 395-2489 min). Only seven patients remained alive at follow-up of 3-46 months.

We have used this approach to treat an 18-year-old female patient with uncontrollable cerebral edema secondary to FHF; she underwent total hepatectomy and portocaval shunt followed by OLT 14 hours later.77 During the anhepatic period she was treated with an extracorporeal liver support system (bioartificial liver) as described in another section of this monograph. With artificial liver support, there was reversal of severe neurological dysfunction, normalization of intracranial pressure and a decrease in serum ammonia. The patient had a complete recovery without any neurologic deficit. A second patient with FHF has also been treated with the same approach at our Unit with a successful long term outcome.

It appears that in highly selected patients with severe "toxic metabolic state" and uncontrollable intracranial hypertension, total hepatectomy and portocaval shunt, preferably with some form of artificial liver support, followed by OLT may be considered as a desperate measure to salvage these patients.

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