**3.1 Auxiliary liver transplantation**

Auxiliary liver transplantation (ALTx) consists of either implanting a healthy liver graft placed heterotopically or orthotopically while leaving all or part of the native liver. This concept was originated from an experimental work of Welch in 1955.[46, 47]

The first auxiliary liver transplantation in human was performed by Absolon in 1964,[48] and it was till 1972 when an auxiliary transplantation truly prolonged a human life.[49] During the following two decades, ALTx was done solely in a heterotopic manner heterotopic auxiliary liver transplantation (HALTx), where a graft (usually partial) is placed below the un-resected native liver. The initial clinical results of HALTx were rather disappointing with a high rate of technical failure, probably due to inadequate portal perfusion of the graft and insufficient drainage of hepatic blood flow in an area of low pressure which had led to temporary abandonment of HALTx in the early 70s.[50-52]

Many efforts have been made ever since to improve post-transplant survival. Most notably, based upon the experiences in animal studies,[52-58] the contributions of Terpstra's group have improved the surgical techniques of HALTx with markedly increased post-HALTx survival rate.[58-63] Since 1980s', the concept of ALTx has further been extended by the introduction of a new approach –auxiliary partial orthotopic liver transplantation (APOLTx), where the left or the right lobe of the native liver is resected and replaced by an auxiliary graft.[64-71] The physiological position of the hepatic graft by this approach results in an optimal outflow pressure. Accumulating clinical results have shown a reduced incidence of post-transplant portal thrombosis.[65, 72, 73]

For certain types of non-cirrhotic metabolic disorders, such as type 1 Crigler-Najjar syndrome, urea cycle enzyme deficiencies, disorders of fatty acid metabolism, familial hypercholesterolemia, hemophilia and ornithine transcarbamylase deficiency, an auxiliary liver may correct the partial enzymatic deficiency responsible for the disease without the need to remove the otherwise normal native liver.[65, 66] A significant minority of patients with acute liver failure who fulfill the transplant criteria would have had complete morphological and functional recovery of their liver if they had not undergone orthotopic liver transplantation.[74] These considerations have led to the concept of auxiliary liver transplantation, which doesn't exclude the potential for spontaneous regeneration of the native liver and eventual withdrawal of immunosuppression drugs.[75-78]

In selected patient aged <40 years without hemodynamic instability, the use of ABO compatible, non-steatotic grafts harvested from young donors with normal liver function, can restore normal liver function and prevent the occurrence of irreversible brain damage. After standard immunosuppression, the recovery of the native liver is assessed by biopsies, hepatobiliary scintigraphy and computed tomography. When there is evidence of sufficient regeneration of the native liver, immunosuppression can be discontinued progressively. Complete regeneration of the native liver can be observed in >50% of patients, who can be withdrawn from immunosuppression. Therefore, the advantages of the auxiliary liver transplantation seem to balance with the potential inconvenience of this technique in

transplantation (LDLT).[44,45] Also, The donor shortage had led to the evolution of hepatocyte and stem cells transplantation which will be the future in the liver

Auxiliary liver transplantation (ALTx) consists of either implanting a healthy liver graft placed heterotopically or orthotopically while leaving all or part of the native liver. This

The first auxiliary liver transplantation in human was performed by Absolon in 1964,[48] and it was till 1972 when an auxiliary transplantation truly prolonged a human life.[49] During the following two decades, ALTx was done solely in a heterotopic manner heterotopic auxiliary liver transplantation (HALTx), where a graft (usually partial) is placed below the un-resected native liver. The initial clinical results of HALTx were rather disappointing with a high rate of technical failure, probably due to inadequate portal perfusion of the graft and insufficient drainage of hepatic blood flow in an area of low pressure which had led to temporary abandonment of HALTx in the early 70s.[50-52]

Many efforts have been made ever since to improve post-transplant survival. Most notably, based upon the experiences in animal studies,[52-58] the contributions of Terpstra's group have improved the surgical techniques of HALTx with markedly increased post-HALTx survival rate.[58-63] Since 1980s', the concept of ALTx has further been extended by the introduction of a new approach –auxiliary partial orthotopic liver transplantation (APOLTx), where the left or the right lobe of the native liver is resected and replaced by an auxiliary graft.[64-71] The physiological position of the hepatic graft by this approach results in an optimal outflow pressure. Accumulating clinical results have shown a reduced

For certain types of non-cirrhotic metabolic disorders, such as type 1 Crigler-Najjar syndrome, urea cycle enzyme deficiencies, disorders of fatty acid metabolism, familial hypercholesterolemia, hemophilia and ornithine transcarbamylase deficiency, an auxiliary liver may correct the partial enzymatic deficiency responsible for the disease without the need to remove the otherwise normal native liver.[65, 66] A significant minority of patients with acute liver failure who fulfill the transplant criteria would have had complete morphological and functional recovery of their liver if they had not undergone orthotopic liver transplantation.[74] These considerations have led to the concept of auxiliary liver transplantation, which doesn't exclude the potential for spontaneous regeneration of the

In selected patient aged <40 years without hemodynamic instability, the use of ABO compatible, non-steatotic grafts harvested from young donors with normal liver function, can restore normal liver function and prevent the occurrence of irreversible brain damage. After standard immunosuppression, the recovery of the native liver is assessed by biopsies, hepatobiliary scintigraphy and computed tomography. When there is evidence of sufficient regeneration of the native liver, immunosuppression can be discontinued progressively. Complete regeneration of the native liver can be observed in >50% of patients, who can be withdrawn from immunosuppression. Therefore, the advantages of the auxiliary liver transplantation seem to balance with the potential inconvenience of this technique in

native liver and eventual withdrawal of immunosuppression drugs.[75-78]

concept was originated from an experimental work of Welch in 1955.[46, 47]

incidence of post-transplant portal thrombosis.[65, 72, 73]

transplantation.

**3.1 Auxiliary liver transplantation** 

selected patients.[79-81] ALTx also preserves the patient's native liver, which remains accessible for future gene transfer therapy.[82]

#### **3.2 Reduced-sized liver transplantation (RLT)**

It was first reported in 1984 by Bismuth, and involves ex-vivo resection of an adult cadaveric liver in order to create an appropriate sized liver graft for an infant or small child. It was introduced as a surgical solution for decreasing the pediatric liver transplant waiting list mortality using organs from donors much larger than the recipient, but does not increase the total number of livers available for transplantation. This is because the reduced-sized portion is not used and discarded.[22]

Initially, RLT was criticized because it disadvantaged adult patients awaiting liver transplantation and was to be associated with inferior results. The allegations regarding inferior graft and patient survival were proven wrong,[83-85] and several proponents of this technique actually reported a lower incidence of vascular complications since the caliber of the hepatic artery was larger than that seen in a pediatric donor.[86] Since this technique resulted in discarding the remaining portion of liver, it clearly had a negative impact on adult population awaiting liver transplantation, and for that reason, is rarely used today.

#### **3.3 Split liver transplantation (SLT)**

In 1988, Pichlmayer in Germany and Bismuth in France simultaneously performed split liver transplantation (SLT), an ex-vivo splitting of a cadaveric liver allowing transplantation to a pediatric recipient and one adult.[23, 87] Unlike RLT, SLT resulted in an increased number of organs in donor pool with each cadaveric liver giving rise to two functioning allografts. The initial results of SLT, reported by Broelsch,[21] had a high rate of graft failure with a survival rate of only 67% in children and 20% in adults receiving a split liver transplants. In addition, 35% of patients required retransplantation and more than a quarter had biliary complications.[22] More recently, in-situ SLT has provided patient and graft survival similar to that seen in whole cadaveric transplantation.[88-90] The practical feasibility of split-liver transplantation as well as the increased safety of conventional liver surgery suddenly opened up the idea of removing part of the liver from a living donor.

#### **3.4 Living donor liver transplantation (LDLT)**

This has been made possible by recent advances in hepatic surgery; first, improved understanding of the anatomy and the techniques of hepatic resections,[91] second, growing evidence that the operative risk of partial hepatectomy in a non-cirrhotic liver is extremely low,[92, 93] third, widespread success with RLT,[25, 83-85, 94] and fourth, the successful application of SLT.[95]

#### **3.4.1 LDLT in pediatrics**

LDLT was first introduced in pediatric population. In 1988, Raia in Brazil reported the first LDLT, establishing the technical feasibility of this procedure, yet both pediatric recipients died of complications.[96] Strong and colleagues subsequently reported the first successful pediatric LDLT using a left lobe graft from the child's mother.[25] Broelsch reported the first successful series of LDLT with an overall graft survival of 75% and patient survival of 85%.[97] Furthermore, he was the first to report a prospective ethical analysis of this radical surgical innovation prior to performing their first LDLT.[98]

LDLT in children involves the removal of an adult donor left lateral segment (segment 2 and 3). Monosegment transplantation (segment 3) was introduced in Japan to solve the problem of "Large for size" grafts in small children.[99] The donor operation has been associated with a low and acceptable risk for complications. The donors being related to the recipients (parents), the risk for the donor is balanced by the great benefit to be received by the transplant recipient, as well as the donor's psychological benefit.

LDLT was initially restricted to children with chronic disease, in relatively stable condition, in order to avoid a major psychological pressure on the potential donor.[98] With larger experience, it was extended to emergency cases such as fulminant hepatic failure. Auxiliary transplantation, initially developed in this indication,[78] and in metabolic disorders,[100] could also be performed with a living donor liver.[101-104]

The continued shortage of cadaver livers in the face of growing list of recipients plus the advantages of LDLT have led to the introduction of LDLT in adults.
