7. Advances in LDLT

the belief that higher portal pressures on the contrary help in liver regeneration [35, 37] thereby

The very first few LDLTs performed were in pediatric patients, utilizing Left Lateral Segment (LLS) liver grafts. This was technically easier for the recipients, whilst offering higher level of donor safety. Both these factors were paramount in gaining the needed success and popularity of LDLT across the world. Meanwhile in adult recipients, right lobe versus left lobe LDLT was debated heavily for two decades. The debate aimed at balancing donor safety and recipient outcomes. Although, logic and ethics favored donor safety, but the recipient risks and outcome were equally important, thus feeding the debate. Normally, the right lobe of the liver is larger and denser than the left lobe, which is much smaller and flatter. Therefore, a left lobe hepatectomy generates a smaller allograft providing higher safety for the donor but limiting the choice of recipient. This blunted the popularity of LDLT in adult patients. But in 1997, the feasibility of using a right lobe liver graft safely in adults by overcoming the graft size matching, opened

In United States, right lobe living donor hepatectomy remained the choice for 95% adult LDLTs, between 1998 and 2009 [40]. Although the number of left lobe living liver donors were smaller for statistical inference, nonetheless, A2ALL consortium concluded, a higher rate of donor complications with left lobe donation. The Turkish group also noted similar findings, whereby performing 91% right lobe LDLTs between 2007 and 2011, they experienced higher donor complications for left lobe liver donation [41]. Arguably both in the US and Turkey, the number of left lobe liver donation was far smaller for a meaningful covariate analysis, instead, it hinted towards the importance of individual surgeon experience in right or left lobe donor

avoiding the need for GIM.

174 Liver Research and Clinical Management

the gateway for adult LDLTs [38, 39].

Figure 6. LDLT patient survival based on BMI [34].

hepatectomy.

6.3. The debate of right vs. left lobe donor hepatectomy

#### 7.1. Dual lobe liver transplant

Donor Safety is paramount to the success of LDLT and also for the transplant program. Therefore, inadequate graft size is a major obstacle, considering the low number of donors willing and suitable to donate. Inadequate graft size along with portal hyper-perfusion can lead to Small For Size Syndrome (SFSS), a clinical syndrome characterized by postoperative coagulopathy and liver dysfunction. Various modes of GIM have been proposed to minimize the portal hyperperfusion and also minimize congestion, but little focus has been on how to encompass the low GRWR. Therefore, dual lobe liver transplant, a technical advancement to the standard LDLT has been described and safely practiced [44] by certain centers. Herein, dual allografts from two separate donors are transplanted heterotopically and orthotopically in one recipient; yielding higher liver volume for better recipient outcome and at the same time, be safer for the living donor(s) (Figure 7). Besides being a technically complex operation, it comes with immunological challenges of acute rejection between the two grafts and the recipient, and also between the grafts itself, including the risk of Graft Versus Host Disease (GVHD).

#### 7.2. ABO-i liver transplant and paired exchange

ABO-incompatible (ABO-i) living donor liver transplants have been in discussion and sparse use for almost three decades, and is reserved for urgent cases only. This is because the fiveyear patient survival rates in adults are abysmally low at 22% [45]. Therefore, ABO-i LDLT has unpopular amongst transplant surgeons. But in 2003, Rituximab, an anti-CD20 monoclonal antibody was introduced in liver transplantation with excellent graft and patient survival rates for ABO-i LDLT [46]. Since then, there have been various immune-modifications by adding plasmapheresis, splenectomy or immunoadsorption columns to Rituximab therapy, in order to successfully cross the blood group incompatibility barrier.

most appropriate recipient. This benefitted the growing need for liver transplant versus the

Trends and the Current Status of Living Donor Liver Transplant

http://dx.doi.org/10.5772/intechopen.74818

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The current decade has been focused on entertaining further advancements not just in tech-

LDLT in summary has come a long way since 1989, and the future progress is yet to be seen in the direction of 3D-bioprinting, cell therapy and crossing the barrier into successful xenotrans-

Section of Transplantation and Immunology, Department of Surgery, Yale School of Medicine,

[1] Starzl TE, Iwatsuki S, van Thiel DH, et al. Evolution of liver transplantation. Hepatology

[2] Pichlmayr R, Ringe B, Gubernatis G. Transplantation of a donor liver to 2 recipients (splitting transplantation): A new method in the further development of segmental liver

[3] Rela M, Reddy MS. Living donor liver transplant (LDLT) is the way forward in Asia.

[4] Fink MA, Berry SR, Gow PJ, Angus PW, Wang B-Z, Muralidharan V, Christophi C, Jones RM. Risk factors for liver transplantation waiting list mortality. Journal of Gastroenterol-

[5] Kim WR, Therneau TM, Benson JT, Kremers WK, Rosen CB, Gores GJ, Dickson ER. Deaths on the liver transplant waiting list: An analysis of competing risks. Hepatology.

[6] Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan

[7] Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. Journal of Clinical Oncol-

transplantation. Langenbecks Archiv für Chirurgie 1988;373:127-130

nique, but in immunosuppression and disease control i.e. hepatitis C treatment.

sparse availability and poor access to deceased donor livers.

plantation.

Author details

References

Ramesh K. Batra\* and David C. Mulligan

Yale University, New Haven, CT, USA

(Baltimore Md). 1982;2(5):614-636

Hepatology International. 2017;11:148

ogy and Hepatology. 2007;22:119-124

2000. International Journal of Cancer. 2001;94:153-156

2006;43:345-351

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\*Address all correspondence to: drrkbatra@gmail.com

Figure 7. Adult to adult living donor liver transplant, using dual grafts [44].

The other alternative to blood group incompatible liver transplant is liver paired exchange. This requires a very high level of coordination between multiple transplant teams as it can be a logistical puzzle. A paired exchange liver transplant in essence, offers superior survival advantage over an ABO-i liver transplant, but the level of communication can strain the system to fail. There are also socio-cultural issues amongst patients in accepting someone else's organ, therefore the success rate of liver exchange matching can be as low as <10% [47]. But its conceptual possibility has been well established with excellent outcomes.

ABO-i liver transplants have a valuable role in patients where socio-cultural barriers deter them from participating in the exchange program. At the same time, certain patients cannot tolerate higher level of immunosuppression and therefore will not be suitable for an ABO-i liver transplant, requiring higher levels of immunosuppression and immune-modulation. But, the availability of multiple options offer valuable and real choices for patients, that meet their individual needs and agrees with their beliefs.

#### 7.3. Tolerance in liver transplant

The liver has been considered very tolerant in solid organ transplantation, but its mechanism is still unclear. Application of regulatory T (T-reg) cells are in experimental stages, but have offered promising early results in solid organ transplantation including LDLT. However, most studies have focused on the applicability and short-term success as of now, but there is a real concern of chronic rejection with auto-antigens in T-reg therapies.

### 8. Summary

After the first decade following the inception of LDLT, there were refinements to the surgical technique and in the process of evaluation to select a suitable donor. There were also lessons learnt on how best to select a suitable recipient for LDLT. After being surgically refined, the second decade offered advancements to the learnt lessons on how to extend the donor acceptance boundaries, and at the same time, how best to match the extended spectrum donor to the most appropriate recipient. This benefitted the growing need for liver transplant versus the sparse availability and poor access to deceased donor livers.

The current decade has been focused on entertaining further advancements not just in technique, but in immunosuppression and disease control i.e. hepatitis C treatment.

LDLT in summary has come a long way since 1989, and the future progress is yet to be seen in the direction of 3D-bioprinting, cell therapy and crossing the barrier into successful xenotransplantation.
