Journal of Hepatology
Volume 46, Issue 4 , Pages 574-578, April 2007

(B) I prefer living donor liver transplantation

Hepato-Biliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, SongPa-gu, Poongap-2dong 388-1, Seoul 138-736, Republic of Korea

published online 05 February 2007.

Article Outline

Abbreviations: ALF, acute liver failure, LDLT, living donor liver transplantation, DDLT, deceased donor liver transplantation, GV, graft volume, TLV, total liver volume, SLV, standard liver volume, APOLT, auxiliary partial orthotopic liver transplantation

 

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1. Introduction 

Although the shortage of brain-dead organ donors is a world-wide problem, the situation is especially serious in Asia. Because of social and cultural issues, deceased organ donation rate remains below five per million population in these regions [1]. In Korea, donation rate is even lower with less than 1.5 donors per million. This resulted in long waiting times and an increasing number of patients dying on the waiting list. To decrease waiting times, living donor liver transplantation (LDLT) has been pursued for years in Asian countries and living donor liver transplantation (LDLT) is now an established option for pediatric and adult patients with end stage liver disease. Patients with acute liver failure (ALF) have the most urgent need for liver transplantation. Even when patients with ALF are managed in large-volume Western liver transplantation centers, transplantation rate ranges between 41% and 72%, and the median waiting time for a graft is 5days [2]. While waiting for a suitable graft, the patient might deteriorate further and eventually lose the life-saving opportunity if transplantation cannot be performed in a timely fashion. Living donors are the only source of organs in countries where the availability of the deceased donors is severely restricted. The use of LDLT for children suffering from ALF has gradually gained acceptance because the procedure’s life-saving potential by far outweighs any ethical aspects [3], [4]. Expansion of LDLT to adult patients with ALF has recently been reported [5], [6] although it not only increases the donor risk, but also the ethical dilemma of donor selection because most of potential donors are likely to be brothers, sisters, children or spouses who are influenced by the imminent death of the patient. Meanwhile, compared with the deceased donor liver grafts, live donor grafts offer distinct advantages, such as more timely transplantation, better graft function and shorter cold ischemia time. However, a satisfactory survival rate of patients with ALF undergoing adult LDLT is a prerequisite to justify the risk for the donor. Extension of LDLT to adult patients with ALF is being reviewed based on the evidence in the literature and our data of 57 ALF patients among 1000 adult LDLTs.

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2. Adult LDLT for ALF at the Asan Medical Center 

Among 1000 adult LDLTs performed between February 1997 and January 2006 at our institution, there were 57 patients with ALF. The decision to perform emergency liver transplantation for patients with ALF was based on King’s College Criteria [7] and/or Clichy Criteria [8]. All patients had evidence of acute hepatic injury accompanied by jaundice and encephalopathy, and extensive necrosis in the explanted liver in the absence of cirrhosis [9]. The fulminant presentations of one patient with Wilson’s disease and one patient with autoimmune hepatitis were included in this retrospective study. Seventy-five percent of our patients underwent LDLT within 3days (median 57h, range 6–152h) after being admitted to our unit (Table 1). To avoid any potential coercion of the live donor candidates, their spontaneous willingness has been ensured by the social worker, the transplantation coordinators, and further by psychologists if necessary. Donors were selected on the basis of blood typing results (ABO typing), liver function test, complete blood cell count, renal function test, serology for hepatitis B and C, coagulation test, cardio-pulmonary work-up (chest X-ray, EKG), the degree of hepatic steatosis (USG, non-enhancing CT, routine percutaneous USG-guided liver biopsy) and the graft/recipient size matching (3-dimensional CT with volumetric analysis). The donor assessment was usually completed within 6h. ABO incompatibility has been regarded as a contraindication to adult LDLT in patients with ALF. Instead of ABO-incompatible donors, we successfully initiated the use of donor exchange program for elective adult LDLT in September 2003 and for urgent adult LDLT in October 2006. The age of the living donors ranged from 16 to 55 (median 29) years (Table 2). According to Korean transplantation law, the permissible donors’ age should be older than 16 years for their parents, and older than 20 years for beyond 2nd consanguinity. The donor–recipient relationship is shown in Fig. 1. To avoid any risk for the donor, the donor’s remnant liver volume should be greater than 30% of total liver volume (TLV) and liver steatosis should be minimal (<10% steatosis). However, if the donor’s remnant liver volume is larger, a higher degree of steatosis can be accepted. As shown in Table 2, the total and the macrovesicular steatosis ranged from 0% to 80% and from 0% to 50%, respectively. Liver grafts with more than 30% of steatosis were not used as single grafts in this high urgency situation, but as dual graft. Forty percent of the estimated standard liver volume (SLV) of the recipient [10] was our minimally required graft volume (GV) to secure the metabolic demands of ALF patients. When the suitability of single graft transplant was in doubt in view of donor safety (small remnant volume <30% of TLV and/or severe steatosis) or small-for-size graft for recipients, dual transplant with two left hemiliver or a combination of a right hemiliver and left hemiliver [11], [12] was performed. This strategy was used in 15 of 57 recipients of a living donor graft (Table 2). To ensure minimal damage to the donors, we preferred to procure lateral segment instead of left hemiliver if the sum of two grafts was estimated to be more than 40% GV/SLV of recipients. In critically ill patients with ALF, the adequate venous drainage of the anterior sector of the right hemiliver graft is crucial to provide sufficient functioning liver mass and to avoid graft congestion. In our series, an extended right hemiliver graft (inclusion of middle hepatic vein to right hemiliver graft) proposed by a Hong Kong group [13] is rarely used (1 of 33 right hemiliver grafts) because of the uncertain donor safety. Modified right hemiliver graft (reconstruction of middle hepatic vein tributaries of right hemiliver graft) [14] was mainly used in 29 of 33 right hemiliver grafts to provide sufficient liver volume and to avoid congestion in both the recipient and the donor. The graft volume weighed between 350g of left hemiliver plus caudate lobe and 970g of dual grafts with a right hemiliver and a left hemiliver, corresponding to 27.2–64.7% of the recipients’ SLV. GV/SLV of the recipients ranged from 27.2% to 81.2% (median 54.6%) (Table 1). All grafts functioned immediately after implantation. In the present series, none of donors suffered from major complications apart from one who developed an intrahepatic pseudoaneurysm after percutaneous needle biopsy. This was incidentally found by a routine post-operative liver CT on day 7 and treated with hepatic artery embolization. All donors were discharged from hospital within 15days and returned to normal preoperative activities. Forty-seven of the 57 recipients are alive at the last follow-up, which ranged from 11 to 107months after LDLT. There were eight in-hospital mortalities (<3months after operation) of the recipients, (3 of 9 left hemilivers with or without caudate, 3 of 33 right hemilivers, and 2 of 15 dual graft recipients. Causes of death were: persistent cerebral edema due to loss of timely operation in 2 patients, massive hemorrhagic necrosis of the graft in 2 patients on day 9 after transplantation, sepsis in 2 patients and treatment refractory acute rejection in 2 patients. There was one re-transplantation with a left hemiliver graft after post-transplant massive hemorrhagic necrosis of left hemiliver plus caudate segment graft, and the patient is now alive. Overall patient survival was 82.3% 1 and 5years after LDLT, respectively. Dual graft transplantation was associated with a better survival rate than single graft transplantation, although this did not reach statistical significance (Fig. 2). Fig. 3 depicts the relationship between graft survival and GV/SLV of the recipients. One-year graft survival of small-for-size liver grafts with GV/SLV <40% was 50%, which was significantly less than that of our minimally required graft volume with GV/SLV ⩾40%. The relatively large-for-size grafts with GV/SLV ⩾50% showed 87.1% of one-year survival rate.

Table 1. Recipient characteristics
CharacteristicsValue
Gender (M/F)32/25
Age (year), median (range)41 (16–77 )
Jaundice to encephalopathy (day), (range)19.5±17.9 (2–100)
Type of fulminant hepatic failure, n (%)
Hyperacute/acute/subacute16 (28.1)/29 (50.9)/12 (21.1)
Hepatic encephalopathy grade, n (%)
Grade I/II/III/IV8 (14.0)/4 (7.0)/17 (29.8)/28 (49.1)
Coma grade, n (%)
Grade 0/I/II/III12 (21.1)/5 (8.8)/12 (21.1)/28 (49.1)
Total bilirubin (mg/dl)30.8±13.5
Prothrombin time (%)21.8±9.0
Creatinine (mg/dl)1.6±1.2
Ventilator, n (%)27 (47.4)
Hemodialysis, n (%)11 (19.3)
Time from admission to operation (h), median (range)57 (6–152)
Graft type (Single/dual), n (%)42 (73.7)/15 (26.3)
GV/SLV%, median (range)54.6 (27.2–81.2)
Single graft50.8 (27.2–81.2)
Dual graft52.4 (45.9–66.2)
Group of GV/SLV%, n (%)
GV/SLV⩾50%31 (54.4)
50>GV/SLV⩾40%21 (36.8)
40>GV/SLV⩾30%4 (7.0)
GV/SLV<30%1 (1.8)
In-hospital mortality, n (%)8 (14.0)

GV/SLV, graft volume/standard liver volume.

Table 2. Donor characteristics
CharacteristicsValue
Gender (M/F)45 / 27
Age (year), median (range)29 (16–55 )
Steatosis (%), median (range)10 ( 0–80)
Macrovesicular type4.7±8.9 (0–50)
Microvesicular type8.0±9.6 (0–50)
Duration of work-up (h), median (range)6 (3–24)
Type of graft, n (%)
Single graft42 (73.7)
Right hemiliver3 (5.3)
Modified right hemiliver29 (50.9)
Extended right hemiliver1 (1.8)
Left hemiliver4 (7.0)
Left hemiliver with caudate segment5 (8.8)
Dual graft15 (26.3)
Right hemiliver+left hemiliver4 (7.0)
Left hemiliver+left hemiliver8 (14.0)
Lateral segment+left hemiliver1 (1.8)
Lateral segment+lateral segment1 (1.8)
Posterior segment+left hemiliver1 (1.8)

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3. Which type of grafts to use in adult LDLT with ALF? 

Although it was suggested that the results of emergency LDLT were inferior to those of elective transplantation [15], LDLT has emerged as a life-saving procedure in adult patients in high-urgency situations [16], [17]. A few centers achieved one-year graft survival rate of 73–90% with a left hemiliver graft that provided 30–35% GV/SLV in adult ALF patients [18], [19]. It has been postulated that patients with ALF might tolerate smaller grafts compared with patients with end-stage chronic liver disease, because ALF is not associated with pre-existing portal hypertension. The successful use of LDLT in an adult patient, using a graft weighing 25% of the recipient’s estimated SLV, was reported by Lo et al. [20]. Also, in the present author’s experience with a left hemiliver plus caudate segment graft, the patient received a graft size of 27.2% of the SLV and survived without prolonged cholestasis and ascites production. However, there were three in-hospital mortalities among nine left hemiliver implantation groups with a mean GV/SLV of 39.2±6.1% (range 27.2–45.4%). Moreover, one-year graft survival of liver grafts with a GV/SLV of less than 40% was 50%, compared to 87.1% in patients with a GV/SLV of more than 50%. To secure uniform success, it is considered mandatory to have a graft size of at least >40%, preferably >50% of the SLV (Fig. 3). Although a left hemiliver graft can be used successfully in adult LDLT in high-urgency situations, a right hemiliver graft which can be twice the size of a left hemiliver graft generally meets the metabolic demands of the recipient even if the donor is smaller in body size than the recipient [21]. LDLT using an extended right hemiliver graft was initiated in 1997 for salvage of adult patients with ALF [5]. Although the initial result of a right hemiliver LDLT was satisfactory, many surgeons have expressed concern about the donor risk because more than 65% of the liver mass has to be removed. Mortality of 0.2% among donors for adult recipients was reported especially after a right hemiliver donation [22]. After realizing that adequate venous drainage of the anterior sector of a right hemiliver graft is essential for the good outcome [13], [14], satisfactory survival has been achieved with LDLT in patients with ALF. Among 33 right hemiliver LDLT recipients, the adequate venous drainage of the anterior sector was obtained in 30 liver grafts (extended right hemiliver in 1, modified right hemiliver in 29) with a one-year graft survival rate of 87.9%. Apart from donor risk, confidence has been fully gained in this operation and, thus, right hemiliver LDLT with an adequate venous drainage of the anterior sector can be offered as one of the best options for adult patients with ALF. The limitation of a right hemiliver LDLT’s applicability is that all the potential donor candidates cannot donate their right hemiliver. Twenty-five percent of potential donors have a large right hemiliver (>70% of their total liver volume) [23], and these donor candidates can donate neither a right nor a left hemiliver to adult recipients because of the increased donor risk after a right hemiliver donation and the small-for-size graft after a left hemiliver donation. But, the sum of two left hemilivers in these unsuitable 25% of potential donors abolishes the handicaps being encountered by a single graft [11]. Two left hemiliver dual grafts provided mean GV/SLV of 50.6±4.5% which was smaller compared to (55.4±10.1%) a single right hemiliver graft. Adult LDLT is an established life-saving therapy, offering survival rates greater than 80%, but it still has several limitations. These include the graft-recipient size mismatches and the use of severe steatotic liver graft (>50% steatosis). Dual graft LDLT has overcome these limitations in adult patients by which two suboptimal partial liver grafts are implanted simultaneously into one recipient. Steatotic liver grafts have been found to have a negative impact on post-transplant graft function and patient survival [24]. In our experience, unilateral severely steatotic (>60% fat) liver graft can be transplanted with satisfactory outcome in patients with ALF if the other graft is only minimally steatotic (<30%) [12].

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4. Advantages of LDLT over auxiliary liver transplantation and cadaveric whole liver transplantation 

Auxiliary partial orthotopic liver transplantation (APOLT) was initially indicated for potentially reversible ALF and non-cirrhotic metabolic liver disease (see article by Jaeck et al. in this Forum) [26]. The dual aim of APOLT for ALF is to allow the native liver to fully regenerate with complete withdrawal of immunosuppression. However, the application of APOLT for ALF remains controversial because APOLT does not uniformly obtain a satisfactory outcome [27]. Meanwhile, while waiting for a cadaveric liver graft, the patient might deteriorate further. Thus, marginal cadaveric liver grafts are frequently used with an incidence of primary graft non-function as high as 13.2% and one-year graft survival rate of 63% [9], inferior to that of LDLT, 75–87% (Table 3). Compared with cadaveric whole liver grafts, live donor grafts offer distinct advantages to patients with ALF such as a higher chance of timely operation and excellent graft function if adequate GV/SLV is provided. Our experience demonstrates that the use of LDLT and the appropriate selection of the graft type remarkably improve the overall survival rate of adult patients with ALF in this region where organ donation from the brain-dead donor is very scarce.

Table 3. Literature review on adult LDLT for ALF
AuthorYearNo. of patientsType of liver graftsGV/SLV GRWR (%)Graft survival (%)
Lo et al. [20]19961Left lobe25100
Kato et al. [25]19971Lateral segment 100
Miwa et al. [18]19994Left lobe35–80100
Uemoto et al. [4]2000158 Left lobe⩾0.7456
8 right lobe
Marcos et al. [6]20001Right lobe0.81100
Nishizaki et al. [19]200215Left lobe23–5475
Liu et al. [21]200216Right lobe39–8987.5
Present study2007579 Left lobe27–8182
33 Right lobe
15 Dual lobes

GV/SLV, graft volume to standard liver volume of recipient.

GRWR, graft recipient weight ratio.

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References 

  1. de Villa VH, Lo CM, Chen CL. Ethics and rationale of living-donor liver transplantation in Asia. Transplantation. 2003;75:S2–S5
  2. Eghtesad B, Bronsther O, Irish W, Casavilla A, Abu-Elmagd K, Van Thiel D, et al. Disease gravity and urgency of need as guidelines for liver allocation. Hepatology. 1994;20:S56–S62
  3. Emond JC, Heffron TG, Kortz EO, Gonzalez-Vallina R, Contis JC, Black DD, et al. Improved results of living-related liver transplantation with routine application in a pediatric program. Transplantation. 1993;55:835–840
  4. Uemoto S, Inomata Y, Sakurai T, Egawa H, Fujita S, Kiuchi T, et al. Living donor liver transplantation for fulminant hepatic failure. Transplantation. 2000;70:152–157
  5. Lo CM, Fan ST, Liu CL, Wei WI, Lo RJ, Lai CL, et al. Adult-to-adult living donor liver transplantation using extended right lobe grafts. Ann Surg. 1997;226:261–269
  6. Marcos A, Ham J, Fisher R, Olzinski AT, Shiffman ML, Sanyal AJ, et al. Emergency adult to adult living donor liver transplantation for fulminant hepatic failure. Transplantation. 2000;69:2202–2205
  7. O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97:439–445
  8. Bernuau J, Goudeau A, Poynard T, Dubois F, Lesage G, Yvonnet B, et al. Multivariate analysis of prognostic factors in fulminant hepatitis B. Hepatology. 1986;6:648–651
  9. Farmer DG, Anselmo DM, Ghobrial RM, Yersiz H, McDiarmid SV, Cao C, et al. Liver transplantation for fulminant hepatic failure; experience with more than 200 patients over a 17-year period. Ann Surg. 2003;237:666–676
  10. Urata K, Kawasaki S, Matsunami H, Hashikura Y, Ikegami T, Ishizone S, et al. Calculation of child and adult standard liver volume for liver transplantation. Hepatology. 1995;21:1317–1321
  11. Lee SG, Hwang S, Park KM, Kim KH, Ahn CS, Lee YJ, et al. Seventeen adult-to-adult living donor liver transplantations using dual grafts. Transplant Proc. 2001;33:3461–3463
  12. Moon DB, Lee SG, Hwang S, Kim K, Ahn C, Park K, et al. Resolution of severe graft steatosis following dual-graft living donor liver transplantation. Liver Transplant. 2006;12:1156–1160
  13. Lo CM, Fan ST, Liu CL, Lo RJ, Lau GK, Wei WI, et al. Extending the limit on the size of adult recipient in living donor liver transplantation using extended right lobe graft. Transplantation. 1997;63:1524–1528
  14. Lee SG, Lee YJ, park KM, Hwang S, Choi DR, Kim KH, et al. Anterior segment congestion of a right liver lobe graft in living donor liver transplantation and its strategy to prevent congestion. (in Korean) J Korean Soc Transplant. 1999;13:213–219
  15. Kam I. Adult-adult right hepatic lobe living donor liver transplantation for status 2 a patients: too little, too late. Liver Transplant. 2002;8:347–349
  16. Lo CM, Fan ST, Liu CL, Wei WI, Chan JK, Lai CL, et al. Applicability of LDLT to high-urgency patients. Transplantation. 1999;67:73–77
  17. Moon DB, Lee SG. Adult-to-adult living donor liver transplantation at the Asan Medical Center. Yonsei Med J. 2004;45:1162–1168
  18. Miwa S, Hashikura Y, Mita A, Kubota T, Chisuwa H, Nakazawa Y, et al. Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure. Hepatology. 1999;30:1521–1526
  19. Nishizaki T, Hiroshige S, Ikegami T, Uchiyama H, Hashimoto K, Soejima Y, et al. Living-donor liver transplantation for fulminant hepatic failure in adult patients with a left-lobe graft. Surgery. 2002;131:S182–S189
  20. Lo CM, Fan ST, Chan JKF, Wei W, Lo RJ, Lai CL. Minimum GV for successful adult-to-adult living donor liver transplantation for fulminant hepatic failure. Transplantation. 1996;62:696–698
  21. Liu CL, Fan ST, Lo CM, Yong BH, Fung AS, Wong J. Right-lobe live donor liver transplantation improves survival of patients with acute liver failure. British J Surg. 2002;89:317–322
  22. Renz JF, Roberts JP. Long-term complications of living donor liver transplantation. Liver transplant. 2000;6:S73–S76
  23. Sugawara Y, Makuuchi M, Takayma T, Imamura H, Kaneko J. Right lateral sector graft in adult living-related liver transplantation. Transplantation. 2002;73:111–114
  24. Marsman WA, Wiesner RH, Rodriguez L, Batts KP, Porayko MK, Hay JE, et al. Use of fatty donor liver is associated with diminished early patient and graft survival. Transplantation. 1996;62:1246–1251
  25. Kato T, Nery JR, Morcos IJ, Gyamfi AR, Ruiz P, Molina EG, et al. Successful living related liver transplantation in an adult with fulminant hepatic failure. Transplantation. 1997;64:415–417
  26. Hoek B, Boer J, Boudjema K, Williams R, Corsmit O, Terpstra OT. Auxiliary versus orthotopic liver transplantation for acute liver failure. J Hepatol. 1999;30:699–705
  27. Kasahara M, Takada Y, Egawa H, Fujimoto Y, Ogura Y, Ogawa K, et al. Auxiliary partial orthotopic living donor liver transplantation: Kyoto University experience. Am J Transplant. 2005;5:558–565

PII: S0168-8278(07)00054-2

doi:10.1016/j.jhep.2007.01.013

Journal of Hepatology
Volume 46, Issue 4 , Pages 574-578, April 2007

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