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Keywords:

  • Left lobe graft;
  • living donor liver transplantation;
  • small-for-size graft;
  • small-for-size syndrome

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Operative mortality for a right lobe (RL) donor in adult living donor liver transplantation (LDLT) is estimated to be as high as 0.5–1%. To minimize the risk to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim of the study was to assess the feasibility of LL-LDLT between adults based on a single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard liver volume of the recipients. The overall 1-, 3- and 5-year patient survival rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with three losses directly attributable to small-for-size graft syndrome. Post-operative liver function and hospital stay in LL donors were significantly better and shorter than that in RL donors, while the incidence of donor morbidity was comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a feasible option in adult-to-adult LDLT. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Living donor liver transplantation (LDLT) was first initiated in children in 1989 in response to a severe organ shortage from pediatric donors (1,2). Since the first successful report on adult-to-adult LDLT published in 1994 (3), the indication for this modality has been actively extended to adult recipients, especially in countries like Japan and other Asian countries where the availability of brain-dead donors is severely restricted. It has evolved to be an accepted and established alternative to deceased-donor liver transplantation (DDLT) in Western countries and is expected to minimize the mortality of patients awaiting transplantation.

At the start of adult LDLT, left lobe (LL)-LDLT was the only option available because of the potential risk for the donor in right lobe (RL)-LDLT. However, the use of LL grafts for adults was severely limited due to their size limitation. Generally, a LL graft can provide only 30–50% of the required liver volume for an adult recipient, and has been thought to be too small for adult recipients to sustain their metabolic demand (4). Recently, RL-LDLT has emerged to overcome the graft size problem, which resulted in a rapid increase in number of cases with yet unknown risks for donors. In the context of these size problems, the concept of LL donation for adult recipients has almost been abandoned, without sufficient data available, especially in the United States and Europe.

The crucial prerequisite to performing LDLT is a minimal morbidity and mortality risk to the healthy living donor. Unfortunately, sporadic donor deaths associated with RL donations have been reported in the United States (5) and Europe (6), as well as in Japan (7). It is reported that operative mortality for the RL donor is estimated to be as high as 0.5–1% (8). To minimize the risk to the donor, LL-LDLT could be an ideal option in adult-to-adult LDLT. However, information on the results of adult-to-adult LL-LDLT is, so far, very scarce.

Therefore, the objective of this study was to assess the feasibility of LL-LDLT between adults based on the largest to date, single-center experience.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Patients

Between October 1996 and March 2005, 182 consecutive LDLTs were performed at Kyushu University Hospital, Fukuoka, Japan, after obtaining approval from the Ethics and Indications Committee of Kyushu University. This comprised 157 adults (aged ≥18 years) and 25 children (aged <18 years). Of the 157 adults, a total of 107 patients underwent LDLTs using LL grafts with (n = 94) or without (n = 13) the caudate lobe, while 50 patients received RL grafts with (n = 2) or without (n = 48) the middle hepatic vein. Comparison of the characteristics of recipients, grafts and donors who underwent either LL-LDLT or RL-LDLT is shown in Table 1. Forty of 60 patients with HCC (including four with incidental HCC) had HCC beyond the Milan criteria. The indications for retransplantation included hepatic artery thrombosis (n = 1), small-for-size graft syndrome (n = 1) and anterior graft congestion after RL-LDLT (n = 1). Thirty-five cases (29 LL, six RL) were highly urgent and received intensive care pre-operatively. The mean model for end stage liver disease (MELD) score in LL and RL was 14.1 ± 7.4 and 14.6 ± 8.3, respectively (p = NS).

Table 1. Patient characteristics
FactorsLeft lobe (n= 107)Right lobe (n= 50) P
  1. *mean ±sd, Abbreviations: FHF, fulminant hepatic failure; GRWR, graft recipient weight ratio; GV, graft volume; HCC, hepatocellular carcinoma; MELD, model for end-stage liver disease; SLV, standard liver volume.

Recipient
 Age (years)49.6 ± 12.950.2 ± 12.8NS
 Sex (M/F)50/5727/23NS
 Body weight (kg)57.0 ± 9.7*64.2 ± 12.00.0001
(range, 40.0–86.0)(range, 34.8–93.4) 
 Etiology (n) 0.0097
 Liver cirrhosis912 
 HCC3722 
 Cholestatic disease2811 
 FHF274 
 Retransplant30 
 Other31 
 Child-Pugh classification (n) 0.0002
 A165 
 B298 
 C3133 
 MELD score (n) NS
 0–103416 
 11–204824 
 21–30208 
 31–4042 
 Status (n) 0.033 
 ICU-bound296 
 Hospitalized3526 
 At home4218 
Graft
 GV (g)452 ± 90 593 ± 82<0.0001
 GV/SLV ratio (%)40.5 ± 8.1 50.5 ± 7.9<0.0001
 GRWR (%)0.81 ± 0.190.95 ± 0.21<0.0001
Donor
 Age (years)35.8 ± 11.737.9 ± 11.8NS
 Sex (M/F)86/2123/27<0.0001
 Blood type (n) NS
 identical8834 
 compatible1815 
 incompatible11 
 Relationship (n) 0.0139
 Father/mother105 
 Son/daughter5824 
 Brother/sister1110 
 Husband/wife239 
 Other52 

Graft selection criteria

At the start of our adult LDLT program in 1997, LL-LDLT was the only option available for all adult patients. Our general selection criteria for grafts in adult-to-adult LDLT included a graft volume-to-recipient standard liver volume (GV/SLV) ratio >30%. However, on some occasions, grafts of GV/SLV <30% were accepted and utilized. In October 1998, we performed the first LDLT using a RL graft for patients with glycogen storage disease. Since then, RL grafts have been used sporadically. From December 2000, we decided to use RL grafts more often, especially for patients whose GV/SLV ratio was going to be <35% if LL grafts were selected or for patients with a high MELD score. Currently, our selection criteria for LL grafts include a predicted GV/SLV >35%, while those for RL grafts include an estimated remnant liver volume ≥35% in the donor. However, graft selection is still carried out on a case-by-case basis, considering various factors including anatomical variations and recipient conditions. Graft weight was measured at the back table after flushing the graft with University of Wisconcin solution.

The indication in patients with HCC included neither extrahepatic metastasis nor macroscopic vascular invasion in conventional imaging studies. We did not set any limitations regarding the size and number of tumors.

Surgical procedure

The transplant procedures for both donors and recipients were described previously (9). Hepatic arteries were always reconstructed under the microscope. Duct-to-duct biliary reconstruction has been a routine procedure since June 2000. Intentional splenectomy (n = 8) or ligation of the proximal splenic artery (n = 12) were added in some patients with LL graft in order to decrease the portal flow, thereby expecting decreased relative hyperperfusion of small-for-size grafts.

Immunosuppression

The immunosuppressive regimen consisted of a combination of calcineurin inhibitor (tacrolimus or cyclosporin) and steroid with or without mycophenolate mofetil. Steroid was tapered off by 6 months after transplantation. Since July 2002, a steroid-sparing regimen including basiliximab (Simulect®, Novartis Pharma AG, Basle, Switzerland) and mycophenolate mofetil has been employed for patients with HCC- or hepatitis C-related cirrhosis. Basiliximab 20 mg was given i.v. within 6 h of graft reperfusion and on post-operative day 4. Steroid injection was given intra-operatively (methylpredonisolone 1000 mg) and tapered off by day 7. Currently, the treatment is completely free of steroids, which are used only intraoperatively for patients with HCC or hepatitis C. Mycophenolate mofetil 1000 mg/day was started from post-operative day 1 and completed by 3 months. Maintenance immunosuppression consisted of low-dose tacrolimus or cyclosporine from post-operative day 7.

Definition of small-for-size graft syndrome

Small-for-size (SFS) graft syndrome is hard to define because it may overlap with other causes of graft dysfunction. However, in order to determine the impact of SFS graft on the outcome, we defined SFS graft syndrome as having both prolonged functional cholestasis and intractable ascites. Prolonged functional cholestasis was defined as total bilirubin >10 mg/dL at post-operative day 14, without any other definitive causes for cholestasis (10). Intractable ascites was defined as a daily production of ascites of >1 l at post-operative day 14 or >500 mL at post-operative day 28. Ascites production was defined as the daily amount of ascites through indwelling drains (plus leakage through the drain orifice).

Statistical analysis

Continuous variables were compared using a two-tailed, unpaired t-test for independent samples. All values are expressed as mean ±sd. Categorical data were compared using the chi-square test. A logistic regression analysis was performed to identify causes for SFS syndrome. Analysis of patient survival was performed using the Kaplan-Meier method and compared between groups using the log-rank test. The p-values <0.05 were considered to be significant. All statistical analyses were done with the StatView® 4.5 software for Macintosh (Abacus Concepts, Berkeley, CA, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

Graft size and its distribution

The mean GV of LL grafts was 452 g (range 220–650 g), which was significantly smaller than that of RL grafts (593 g, range 400–760 g, p < 0.0001). The mean GV/SLV ratio and graft-to-recipient weight ratio (GRWR) were 40.5% (range 21–66.1%) and 0.81% (0.41–1.51%), respectively in LL grafts, which were, again, significantly smaller than those of RL grafts. Figure 1 depicts the graft size distribution of LL and RL grafts according to the GV/SLV ratio. Ten LL grafts were extremely small, namely, GV/SLV <30%. The smallest one was a LL graft of GV/SLV 21%, for which auxiliary partial orthotopic liver transplantation was performed in patients with primary screlosing cholangitis (11).

image

Figure 1. Graft size distribution according to GV/SLV ratio. Mean GV/SLV ratio in LL and RL grafts was 40.5 ± 8.1% and 50.5 ± 7.9%, respectively.

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Overall patient and graft survival rates

The mean follow-up after transplant was 1044 days (range: 4–2982 days) in LL grafts and 541 days (range 22–1646 days) in RL grafts (p < 0.0001). The cumulative overall 1-, 3- and 5-year patient survival rates were 81.4, 76.9 and 74.7%, respectively, in patients with LL grafts, which were not significantly different from those of patients with RL grafts (Figure 2). The cumulative 1-, 3- and 5-year graft survival rates were 79.1, 74.7 and 72.6%, respectively, in LL grafts, which were not significantly different from those of RL grafts (data not shown). Figure 3 shows patient survival in LL grafts according to the GV/SLV ratio. The GV/SLV ratio was classified into four groups as follows: <30% (n = 10); ≥30%, <40% (n = 34); ≥40%, <50% (n = 47) and ≥50% (n = 11). Although grafts of GV/SLV ≥50% tended to show worse prognosis, graft size itself did not influence the survival rates. Grafts of GV/SLV ≥30%, <40% demonstrated the best result with 1-, 3- and 5-year patient survival rates 91, 86.6 and 81.5%, respectively.

image

Figure 2. Comparison of cumulative patient survival between LL- and RL-LDLT.

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image

Figure 3. Comparison of cumulative patient survival according to GV/SLV ratio. The log-rank test found no statistically significant differences.

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Operative outcomes

Figure 4 shows the comparison of operative outcomes between LL and RL grafts. The mean operative time was significantly shorter in LL grafts (766 ± 154 min) than that of RL graft (849 ± 182 min, p < 0.01). Blood loss as well as the use of red blood cells tended to be less in LL grafts, but it did not reach statistical significance.

image

Figure 4. Comparison of operative data between LL- and RL-LDLT. A, operative time; B, estimated blood loss and C, amount of transfusion of packed red blood cells.

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Cause of graft loss

Table 2 shows the cause of graft loss both in LL grafts and RL grafts. Of the 107 LL grafts, 26 were lost to hepatic artery thrombosis (n = 2), chronic rejection (n = 2), hepatic infarction (n = 4), graft dysfunction/sepsis (n = 3), SFS graft syndrome/sepsis (n = 3), graft-versus-host disease (n = 1), recurrent hepatitis C (n = 2), recurrent HCC (n = 4), de novo malignancy (n = 1) and other causes (n = 4) including portal vein thrombosis (n = 1), hepatic infarction due to precutaneous transhepatic biliary drainage (n = 1), pancreatic juice leakage leading to arterial disruption (n = 1) and brain herniation (n = 1). In RL grafts, cause of graft loss consisted of recurrent hepatitis C (n = 2), recurrent HCC (n = 1), multiple liver abscess (n = 1), graft dysfunction/sepsis (n = 5), anterior segment congestion (n = 1) and other causes (n = 1).

Table 2. Cause of graft loss
CausesLeft lobe (n= 107)Right lobe (n= 50)Total
  1. Abbreviations: HAT, hepatic artery thrombosis; GVHD, graft-versus-host disease; SFS, small-for-size.

HAT202
Chronic rejection202
Hepatic infarction404
SFS graft syndrome302
Graft dysfunction/sepsis358
Congestion011
GVHD101
Disease recurrence639
De novo malignancy101
Others426
Total26 (24.2%)11 (22%)39

Incidence of small-for-size graft syndrome

We identified SFS graft syndrome in 27 (25.2%) patients with LL grafts while only in three (6%) with RL grafts (p < 0.01). In LL grafts, the mean GV/SLV ratio in patients who developed the syndrome was 36.2%, which was significantly smaller than that in patients who did not develop the syndrome (41.9%, p < 0.01). If we plotted the graft size according to the existence of portal hypertension or cirrhosis, patients with portal hypertension tended to develop SFS graft syndrome more frequently (22/76, 28.9%) as compared to patients without portal hypertension (5/31, 16%), although the difference did not reach statistical significance (Figure 5A). If we stratified the incidence by the Child classification, Child B (10/29, 34.5%) or C (8/31, 25.8%) patients developed SFS graft syndrome more frequently than Child A (3/16, 18.8%) patients, even when the graft size was relatively large (Figure 5B). In Child A patients, none developed SFS graft syndrome if graft size exceeded 35%. However, A logistic regression analysis including the presence of cirrhosis, graft type (LL or RL), GV/SLV ratio, MELD score and Child-Pugh classification revealed that only GV/SLV ratio was significant (relative risk, 0.901; 95% confidence interval, 0.840–0.966; p < 0.0008). The 1-, 3- and 5-year patient survival rates in patients who develop the syndrome were 74.1, 67.9 and 67.9%, respectively, which were comparable to those of patients who did not develop the syndrome (83.5, 79.7 and 77%, respectively).

image

Figure 5. Incidence of small-for-size graft syndrome according to presence of cirrhosis (A) and Child-Pugh classification (B). Open circles represent patients with small-for-size (SFS) graft syndrome. Closed circles represent patients free from SFS graft syndrome.

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Donor morbidity

In terms of donor post-operative liver functions, including peak aspartate aminotransferase, alanine aminotransferase and peak total bilirubin, those of LL donors were significantly lower than those of RL donors (Figure 6). However, the morbidity rate did not show evidence of a difference between the two groups (Table 3). None of the complications led either to mortality or to long-term sequelae in either group. The mean post-operative hospital stay in LL donors was 11.2 days, which was significantly shorter than that in RL donors (20.2 days, p < 0.01). Only one relaparotomy was performed for a LL donor (case 10) due to biliary stricture caused by a stitch on the bile duct. These data clearly suggest that LL donation is potentially safer than RL donation, although no donor mortality was seen in either group.

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Figure 6. Comparison of post-operative liver function tests between LL- and RL-donor. (A) Peak aspartate aminotransferase. (B) Peak alanine aminotransferase. (C) Peak total bilirubin.

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Table 3. Donor morbidity
Complications (n)Left lobe (n= 107)Right lobe (n= 50)Total (%)
Arm paralysis314 (2.5%)
Bile leakage156 (3.8%)
Bile duct stricture235 (3.2%)
Peptic ulcer202 (1.3%)
Depression022 (1.3%)
Iatrogenic hemothorax011 (0.6%)
Gastric stasis404 (2.5%)
MRSA infection101 (0.6%)
Alopecia426 (3.8%)
Total17 (16%)14 (28%)31 (20%)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References

With the increasing success of LDLT as a modality for adult patients with end-stage liver disease, the demand for this procedure continues to grow. In 2004, 323 LDLTs (5.2% of the total) were performed in the United States, while 5844 DDLTs were performed (12). The total number of LDLTs reached 2623 cases by the end of 2004. In Japan, a total of 2667 LDLTs had been accumulated by the end of 2003 and it exceeded 3000 by the end of 2004, while only 28 DDLTs had been performed as of June 2005. In Europe, 675 LDLTs have been performed since 1991, of which 276 (41%) were carried out in adults (13).

Which type of graft should be used for adult-to-adult LDLT, LL or RL? All forms of LDLT are subject to varying degrees of complications and mortality, depending on the complexity of the procedure, and despite good intentions and experienced hands, there can be no argument that there is a definite mortality risk to the donor. Undoubtedly, the safety of donors must have priority when considering LDLT and the inevitable risk for donors must be balanced against the potential benefit for the recipient. However, the risks of living donation are difficult to quantify. It is conceivable that the LL donation is potentially safer than RL donation because the remnant volume of the liver may be larger. In fact, Umesita et al. (14) reported on the incidence of donor complications based on 1853 donors from the Japanese Registry of LDLT. The incidence of complications was significantly higher in donors of RL than LL and lateral segment grafts. Lo CM et al. (15) also reported the incidence of donor complications based on a survey of 1508 cases in five Asian centers. Again, the complication rate was higher in RL (28%) donors than in left lateral segment (9.3%) or LL (7.5%) donors. Moreover, RL donors had more serious complications such as cholestasis (7.3%), bile leakage (6.1%), biliary stricture (1.1%), portal vein thrombosis (0.5%), intra-abdominal bleeding (0.5%) and pulmonary embolism (0.5%). However, our data did not demonstrate statistically significant difference in complication rates between RL and LL donors. RL donation is known to be associated with significant hyperbilirubinemia and prolonged prothrombin time after surgery, although these usually resolve spontaneously without any adverse sequelae. The most serious potential consequence of a right lobectomy or extended right lobectomy is death of the donor. To the best of our knowledge, at least 10 donors have died to date after living donation worldwide. Among them, eight deaths occurred after RL donation in Japan (n = 1), Brazil (n = 1) (16), the United States (n = 2) and Europe (n = 4). However, even in LL-LDLT, the possibility of donor mortality is real because at least two deaths have been reported in lateral segment graft donors in the United States (n = 1) and Europe (n = 1). Nonetheless, it is clear that RL donation carries significantly more risks than LL donation.

Balancing the safety of the donor with a satisfying outcome of the recipient is a key issue in the process of living donation. Can LL graft be sufficient to sustain the metabolic demand of adult recipients? The initial report of 13 LL-LDLTs between adults by Kawasaki et al. (17) revealed satisfactory results in both donors and recipients, with 11 out of 13 patients surviving. However, their cohort included seven cases of metabolic disease that may have normal liver function. Tanaka K et al. (18) reported in their early series of 39 LL-LDLTs that survival was 82.1% in patients with a GRWR ≥0.8 (n = 28), but only 54.5% in those with a GRWR <0.8 (n = 11). Based on these unsatisfactory results, they have adopted RL graft to overcome this size problem. Almost all reports from the United States (19–21), Hong Kong (22), Europe (23) and Japan (24) advocate the superiority of RL-LDLT in view of recipient safety. On the other hand, survival data in the LL-LDLT cohort were comparable to those of the RL-LDLT cohort, although the LL recipients were significantly smaller, far less likely to have portal hypertension (more likely to be patients with fulminant hepatic failure) and have lower Child-Pugh score. Moreover, patient and graft survival rates were comparable to those of RL-LDLT published to date from other institutions (19–25). These results suggest that LL-LDLT, if carefully and properly selected, could offer the same result as RL-LDLT. More precisely, in less sick smaller patients, the outcomes of LL-LDLT are comparable to those of RL-LDLT whose recipients are relatively larger and more sick. Therefore, experienced LDLT centers may contemplate the use of LL grafts in selected patients for a potential, but yet unproven decrease in donor morbidity. In other words, RL-LDLT is not uniformly necessary for all adult patients.

Therefore, the question arises: does graft size really matter in the setting of LDLT? Is it really necessary to subject donors to a more risky procedure like RL-LDLT? In terms of graft size, we previously demonstrated that graft size per se does not influence outcome (26). Our present data show that graft size itself does not directly influence patient survival rate in LL-LDLT. On the other hand, Kiuchi et al. (27) analyzed the influence of graft size on the outcome of LDLT and showed that the use of SFS grafts (<1% of recipient body weight) led to lower graft survival, probably through enhanced parenchymal cell injury and reduced metabolic and synthetic capacity. However, in addition to the donor risks, RL grafts confer many problems such as reconstruction of venous tributaries draining the anterior segment of the liver (27,28) and increased incidence of biliary complications due to anatomical variations (29,30). On the other hand, anatomical variations of the LL graft are usually simple and easily managed.

As to the SFS graft syndrome, our present data revealed that SFS graft syndrome did occur in 25% of patients with a LL graft. We also found that SFS graft syndrome did not necessarily lead to graft loss. Only three patients lost their graft directly due to SFS syndrome. The SFS graft syndrome is characterized clinically by a combination of prolonged functional cholestasis, intractable ascites and a delayed recovery of both prothrombin time and encephalopathy (4). However, it is often difficult to discriminate SFS graft syndrome with other complications because of possible symptom overlap. It is known that the syndrome is often multifactorial. Furthermore, the characteristics of this syndrome have not been fully examined in a large series of patients. The mechanism of SFS graft syndrome remains unknown. When transplanted under conditions of portal hypertension, small grafts are supposed to be exposed to a relatively excessive portal perfusion and pressure, as compared to grafts under normal portal pressure. Experimental data suggest that hyperperfusion of the liver is detrimental and improved results are obtained with portal decompression of small grafts (31). In addition, gut derived endotoxin and substrates, including fatty acids, may further deteriorate the small graft after reperfusion (4). Clinically, some groups have advocated the use of temporal portocaval shunt to reduce or minimize the influence of such substances accumulating during portal clamping (32). There are some reports of successful LDLT using a very small graft by making a portocaval shunt, which diverts excessive portal flow to the systemic circulation, thereby reducing liver hyperperfusion (33,34). Our unpublished data suggest an association between SFS graft syndrome and the amount of portal flow after transplantation. Therefore, our current approach in managing the problem of SFS grafts is to reduce the relatively excessive portal flow by ligating the proximal splenic artery or performing splenectomy, if necessary (35). As to the susceptibility to such syndrome, we previously reported our initial experience of 50 LDLTs using LLs and proposed that minimum graft volume in adult-to-adult LDLT should be a GV/SLV ratio >30% for recipients without cirrhosis and >45% for patients with cirrhosis (11). The Mount Sinai group reported that pre-transplant disease severity of recipients is one of the important factors involved in developing SFS syndrome (36). They analyzed 22 adult recipients who received LL (n = 10) or RL grafts (n = 12) from living donors. Child B or C recipients who received small grafts (GRWR <0.8%) had an inferior graft survival of 25% (1/4), whereas the graft survival of Child A recipients was 100% (8/8) without showing any symptoms related to SFS grafts. They conclude that the pre-transplant disease severity significantly affects the graft survival of recipients with SFS grafts.

With refinement of surgical procedures and better graft selection, we have achieved significant progress in outcomes. The 1-year patient and graft survival rate in the last 50 cases is now >90% (Figure 7). We therefore currently think that, with appropriate graft size matching and careful recipient selection, adult-to-adult LDLT can be successful with either a left or a right lobe.

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Figure 7. Trend in patient survival after adult-to-adult LDLTs. Better results have been archived in the last 50 cases with a 1-year survival rate of 90.4%.

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In conclusion, adult-to-adult LL-LDLT was found to be feasible without affecting patient and graft survival rates. Further utilization of LL grafts should be undertaken to keep the chance of donor morbidity and mortality minimal.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. References