Donor shortage is a major issue in liver transplantation. We have successfully performed temporary auxiliary partial orthotopic liver transplantation (APOLT) using a small volume graft procured from a living donor for recipients with familial amyloid polyneuropathy (FAP). The aim of this study was to evaluate this procedure by comparing it with standard living donor liver transplantation (LDLT). We compared 13 recipients undergoing this procedure with 23 recipients undergoing a standard LDLT for the treatment of FAP. The estimated donor graft volume and the graft volume/recipient's standard liver volume ratio were significantly smaller in the temporary APOLT group than in the standard LDLT group. Postoperative complications were comparable, although the hospital stay was longer in the temporary APOLT group. All the patients safely underwent a remnant native liver resection about 2 months after their first operation in the temporary APOLT group. No symptoms related to FAP developed before the remnant liver resection, and no significant differences in graft and patient survival were observed between the two groups. We successfully performed temporary APOLT using a small volume liver graft without postoperative liver failure for FAP. Temporary APOLT for FAP might be a useful alternative procedure for expanding the donor pool for LDLT.
variant transthyretin with a methionine-for-valine substitution at position
National Institutes of Health
prothrombin time international normalized ratio
standard liver volume
Technetium 99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin
Donor shortage is a major issue in liver transplantation, although a recently revised law has gradually enabled the deceased donor pool to be expanded in Japan. Therefore, living donors are still the main sources for patients requiring liver transplantation. We have tried to extend the indications for living donor liver transplantation (LDLT) for adult patients using a graft of the left lobe with the left-side caudate lobe (1) since our first successful LDLT in an adult in 1993 (2). One of the major problems in performing LDLT for adult patients is that the graft from the living donor does not always have a sufficient volume. We have reported that the graft volume (GV) requires more than 30% of the recipient standard liver volume (SLV) to prevent posttransplant liver failure (3,4). A right hepatic lobe graft procured from a living donor is one option that has been performed in some institutions (5,6). However, this option should be exercised cautiously, especially in cases where the predicted volume of the donor's remaining left lobe will be relatively small after a right hemihepatectomy. Recently, living donor mortality because of postoperative liver failure has been reported (7–11). Because the safety of the living donor is essential for LDLT procedures, we have strictly limited the use of a right-lobe liver graft to cases where the donor remnant liver volume is more than 35% of the entire liver volume (4).
Auxiliary partial orthotopic liver transplantation (APOLT) was initially introduced as a temporary or permanent support for patients with potentially reversible fulminant hepatic failure (12), and its indications have been extended to congenital metabolic disorders of the liver using a graft procured from a living donor (13). APOLT for metabolic disease has a possible advantage in that the remnant native liver may work as a reservoir, sustaining insufficient graft function—such as that for small-for-sized grafts—immediately after transplantation.
Familial amyloid polyneuropathy (FAP) is a hereditary form of systemic amyloidosis with an autosomal dominant pattern. It usually involves the peripheral nerve system. The variant transthyretin (TTR) with a methionine-for-valine substitution at position 30 (Met30TTR) is the most common form of the amyloid precursor protein in this disease. TTR is produced mainly by the liver and, in small amounts, by the choroid plexus and retina (14). Symptoms usually start during the third or fourth decade of life, and patients usually die within 10–15 years. Liver transplantation has become a standard treatment for FAP since Holmgren et al. first reported this procedure (14), as it is the only therapy to permanently terminate the production of Met30TTR by the liver. We have performed LDLT for patients with FAP since our first success with this procedure (15,16).
In 2000, we reported a successful temporary APOLT procedure performed using a significantly small left hemiliver graft procured from a living donor, followed by the removal of the remnant native liver, in a patient with FAP (17). Since this initial experience, we have performed a total of 13 temporary APOLTs for FAP recipients using small left-lobe grafts.
The objective of the present study was to investigate the short- and long-term clinical outcomes of temporary APOLT for adult recipients with FAP in the Shinshu University LDLT program.
Patients and Method
Thirteen recipients who had undergone temporary APOLT for FAP at Shinshu University Hospital between 2000 and 2010 were included in this study. To evaluate this procedure, we compared these 13 recipients with 23 recipients who had undergone a standard LDLT for FAP. We retrospectively investigated the following factors between the two groups: recipient and donor characteristics, preoperatively estimated GV, GV versus recipient's SLV ratio, intraoperative findings, postoperative complications and outcome.
The donor hepatectomy procedure was decided based on the match between the liver GV estimated preoperatively using computerized axial tomography (CAT) scan volumetry (18) and the recipient's SLV, calculated from their body surface area (19). We have accepted donor–recipient combinations that produce a predicted GV/SLV ratio equal to or greater than 30%. The GV and whole liver volume in potential donors were measured using CAT scan imaging (5-mm slices) and NIH imaging software (version 1.63, National Institute of Health, Bethesda, MD, USA) or Image J software (Scion Corporation, Fredrick, MD, USA). The recipient SLV was calculated using the following formula (19):
A temporary APOLT is indicated for recipients in whom the GV/SLV ratio has been calculated to be below 30%. We excluded the percentage of fatty liver, evaluated using MRI (20), from the estimated GV for donors with fatty livers.
Informed consent was obtained from the recipient and the donor, both of who accepted the risks and benefits of temporary APOLT, and the university's ethics committee approved the procedures.
The organ procurement technique and graft preservation have been described previously (21,22). Briefly, the left hemiliver was procured by parenchymal transection from a living donor. University of Wisconsin preservation solution was infused into the graft through the portal vein on back table, and the actual GV was measured.
The recipient procedure has also been described elsewhere (23). Briefly, the left hemiliver with the middle hepatic vein (Couinaud segments 2, 3, 4 and left part of subsegment 1) or the left trisegments (Couinaud segments 2, 3, 4, 5, 8 and left part of segment 1) were removed from the recipient in the same way as for the donor operation after the division of the vascular structures supplying the removal liver. We performed a left hemihepatectomy in the first 10 cases, and then changed the procedure to a trisegmentectomy in the last three cases to make the subsequent remnant liver resection both easier and safer (24). The left hemiliver graft was orthotopically positioned by reconstructing the middle and left hepatic vein as well as the left portal vein (Figure 1). We maintained the right or right posterior segment portal vein blood flow during reconstruction before hepatic reperfusion to avoid intraoperative portal venous congestion. The right portal vein was ligated and divided after hepatic reperfusion to induce the atrophy of the remnant liver and the enlargement of the graft liver (23).
The hepatic artery was anastomosed between the graft's and recipient's left hepatic arteries under a microscope, followed by biliary reconstruction, including the anastomosis of the graft's left hepatic duct to the jejunum in seven recipients (Figure 1A), to the recipient's left hepatic duct in four (Figure 1B) and to the recipient's common hepatic duct in three (Figure 1C).
We removed the recipient remnant native liver after the sufficient enlargement of the graft liver, which was judged when the GV/SLV ratio had reached more than 40% on a CAT scan volumetry performed 2 months after the APOLT.
Postoperative care for recipients
Immunosuppression for the recipients basically consisted of tacrolimus and methylprednisolone (25,26). In patients without rejection under a stable tacrolimus-based regimen for 6 months, the methylprednisolone was discontinued.
We evaluated postoperative complications, such as thrombosis, bleeding, acute rejection, infection and biliary stricture, according to the Clavien Grading systems (27).
Data are expressed as the mean ± standard deviation or median. The statistical analysis was performed using a generalized chi-square test, unpaired t-test, or a repeated measure ANOVA using StatView software, Version 5.0 (SAS Institute Inc., Cary, NC). The actuarial 1-year and 5-year graft and patient survival curves were calculated using the nonparametric Kaplan–Meier method, and a log-rank test was used to compare the two groups. p-values of less than 0.05 were regarded as significant throughout the study.
Potential donors were evaluated according to liver function test results, blood group, anatomical variation and graft size based on CAT scan volumetry. All the donors had undergone a TTR gene diagnosis and were found to be negative for the TTR gene mutation. The living donors were related to the recipients as follows: six parents, six siblings and one spouse in the temporary APOLT group; and eight siblings, eight spouses, four parents, two children and one cousin in the standard LDLT group.
The estimated GV and the estimated GV/SLV ratio were significantly smaller in the temporary APOLT group than in the standard LDLT group although the mean height and weight of the donors were comparable (Table 1). The GV/donor's whole liver volume ratio was relatively low in the temporary APOLT group, indicating that these potential donors could not donate their right hemilivers because their remnant left hemiliver would have been too small to sustain their life after the donor hepatectomy. All the living donors are alive and have returned to their normal lives.
Table 1. Characteristics of living donors
Temporary APOLT (n = 13)
Standard LDLT (n = 23)
*L = left hemi-liver; **L + C = left hemi-liver + caudate lobe; GV/SLV = graft volume / standard liver volume.
Sex (male/ female)
(.47.7 ± 13.1
44.3 ± 8.9
Body weight (kg)
60.0 ± 7.7
61.7 ± 9.7
162.0 ± 7.1(.
165.6 ± 6.6(.
Graft type(L*/L + C**)
Blood type identical / Compatible
Estimated GV/SLV (%)
28.7 ± 4.6
38.9 ± 6.9
(range: 22.2 ∼ 35.4)
(range: 28.8 ∼ 48.2)
The mean height and weight of the recipients in the APOLT group were significantly larger than those in the LDLT group (Table 2).
The mean graft weight measured intraoperatively in the temporary APOLT group was significantly lower than that in the standard LDLT group. The GV/SLV ratio and the GRWR were also significantly lower in the temporary APOLT group than in the standard LDLT group. These results indicated that smaller grafts were used more frequently in the temporary APOLT group than in the standard LDLT group.
Operation and postoperative liver function
Intraoperative blood loss and the cold ischemia time were comparable between the two groups (774 ± 359 mL vs. 742 ± 412 mL [p = 0.82] and 110 ± 14 min vs. 121 ± 39 min [p = 0.32], respectively), although the operation took significantly longer in the APOLT group than in the LDLT group (895 ± 120 min vs. 819 ± 75 min, p = 0.02). The postoperative serum total bilirubin level and the prothrombin time international normalized ratio (PT-INR) were significantly lower in the temporary APOLT group than in the standard LDLT group, although the serum aspartate amino transferase (AST) levels were comparable (Figure 2). These findings indicated that the temporary APOLT procedure could be performed with a safety level comparable to that of standard LDLT.
Postoperative complications in recipients
The postoperative complications are shown according to the Clavien Grading systems in Table 3. Although some severe complications, such as thrombosis and intraabdominal bleeding, required surgical reoperation in both groups, no complications of Clavien Grade V occurred in the temporary APOLT group. Each complication belonging to each Clavien Grade was not significantly different between the two groups.
Table 3. Postoperative complications of recipient
Temporary APOLT (n = 13)
Standard LDLT (n = 23)
CMV = cytomegalovirus.
Portal vein thrombosis
Acute cellular rejection
Portal vein stenosis
Hepatic vein stenosis
Portal vein thrombosis
Portal vein thrombosis
Hepatic arterial thrombosis
Acute cellular rejection
Portal vein thrombosis
Hepatic arterial thrombosis
All the patients except one safely underwent a remnant liver resection about 2 months after transplantation in the temporary APOLT group. No symptoms related to FAP developed during the interval between the temporary APOLT and the remnant liver resection. One patient developed both arterial and portal thrombosis simultaneously because of severe dehydration related to abnormal sweating and repeated vomiting arising from the primary disease, at 5 days after transplantation; we decided to remove the graft and to reconstruct the transected right branch of the portal vein to the native liver. One year after this episode, the recipient underwent a successful retransplantation (standard LDLT) using another graft obtained from her husband.
Enlargement of the graft after temporary APOLT
To evaluate the anatomical and functional enlargement of the graft, we performed a CAT scan volumetry examination and technetium 99-galactosyl serum albumin (GSA) scintigraphy 2 months after the temporary APOLT. The estimated CAT scan volumetry results showed a graft size of 610.3 ± 185.7 mL and a remnant native liver volume of 439.0 ± 111.1 mL (the ratio of the GV and remnant native liver volume per whole liver [graft plus remnant liver] volume, 58%:42%). The graft size had increased by 181.7 ± 61.0% (Figure 3A) and the remnant liver had decreased to 66.2 ± 18.7% (Figure 3B), compared with the volumes at the time of the temporary APOLT. The GV/SLV ratio had increased from 30.7% to 52.8% at 2 months after the transplantation.
The GSA scintigraphy study showed tracer uptakes of 65.4% and 34.6% in the graft and remnant liver, respectively, compared with that in the entire liver (graft + remnant liver). This finding indicated that the graft function had also increased to a level sufficient to sustain the recipient's life without liver failure at 2 months after the temporary APOLT.
Remnant liver resection
We removed the remnant liver at a median of 63 days (ranging from 49 to 76 days) after the temporary APOLT. In the first case, the dissection of the graft from the vena cava was difficult because of the strong adhesions surrounding the remnant liver when the remnant liver resection was performed 49 days after the temporary APOLT. Thereafter, we performed the remnant liver resection at least 2 months after the temporary APOLT.
The operation for the remnant liver resection took 443.3 ± 109.3 minutes, and the blood loss was 720 ± 350 g. The hepatic pedicle of the remnant liver and biliary anastomosis were adhered to the surrounding tissues such as the vena cava and the cut surface of the remnant liver, resulting in an extended operation time. In particular, the cut surfaces between the graft and remnant liver were tightly adhered, and the hepatic parenchyma needed to be redivided.
Postoperative complications in the recipients after native liver resection
No severe complications occurred and none of the patients required a relaparotomy because of complications after the native liver resection. One patient had an episode of acute rejection at 7 days after the native liver resection, which was successfully treated using steroid pulse therapy. Six patients experienced pleural effusion and underwent US-guided thoracentesis. Although six patients were infected with CMV, all were successfully treated with ganciclovir.
The hospital stay of the recipients was longer in the temporary APOLT group than in the LDLT group (146.1 ± 119 and 70.4 ± 36.4 days, respectively, p = 0.0015).
Causes of death
A total of three recipients died within 1 year after transplantation; all three patients had received a standard LDLT. The causes of death included acute rejection, aspergillosis and simultaneous hepatic artery and portal vein thrombosis.
Four other recipients died of cerebral infarction and uterine cancer in the standard LDLT group and sepsis and an accident in the temporary APOLT group at between 1 and 5 years after transplantation. None of the recipients died because of graft failure during this period, and these deaths occurred in recipients who had normal liver function after resuming their normal lives.
Recipient and graft survival rates
The overall 1-year and 5-year patient and graft survival rates were 100% and 81.5% for the patients and 92.3% and 83.9% for the grafts in the temporary APOLT group, and 87.0% and 76.3% for the patients and 87.0% and 76.3% for the grafts in the standard LDLT group, respectively (Figures 4A and B). No significant differences in the 1-year and 5-year patient and graft survival rates were observed between the two groups.
Outcome of living donors
All the complications experienced by the living donors were within Grade IIIa according to the Clavien Grading System, including gastric volvulus in six patients, bile leakage in two patients, and portal vein thrombosis in one patient. Although gastric volvulus was the most common complication in our series, all the cases were successfully treated by endoscopic replacement (28). The portal vein thrombosis was successfully treated by thrombolytic therapy. The hospital stay of the donors was comparable between the temporary APOLT and the standard LDLT groups (24.5 ± 8.5 and 22.3 ± 11.2 days, respectively, p = 0.56). None of the donors required a relaparotomy because of complications, and all the donors were able to resume their normal lives after their discharge from the hospital.
We successfully performed temporary APOLT using grafts with a significantly lower GV/SLV ratio than those used for standard LDLT, followed by native liver resection without posttransplant liver failure. The recipients in the temporary APOLT group were taller and heavier than those in the standard LDLT group, although the characteristics of the donors were comparable. The temporary APOLT recipients would not have been able to obtain an adequately sized graft from a living donor in a standard LDLT setting because the donor's left hemiliver would have been too small to maintain the recipient's life as a liver graft and to maintain the donor's life without liver failure after a donor right hemihepatectomy. We were able to perform liver transplantations safely for recipients with a large physique using a small partial graft and a temporary APOLT procedure.
Technical improvements have made an extended hepatectomy of as much as 70% to 75% of the whole liver tolerable in patients without cirrhosis (5, 29), and living donor right hemihepatectomy of up to 70% of the donor whole liver has been frequently performed worldwide. Although the reported minimum GV/SLV ratio for a successful adult-to-adult LDLT is 20% (30), we have a policy of not accepting grafts with a low GV/SLV ratio because a second graft would be difficult to obtain if the recipient developed posttransplant liver failure in an LDLT setting. Lo et al. recommend a GV/SLV ratio of more than 40% (31), and Kiuchi et al. recommended a graft-to-recipient weight ratio (GRWR) of 0.8% to achieve good graft and recipient survival rates (32). We previously reported that a preoperatively evaluated GV/SLV ratio of 30% to 35% was acceptable for LDLT donors (4). We have thus selected temporary APOLT for the treatment of patients for whom only a small graft can be procured from a living donor.
The postoperative serum bilirubin level and PT-INR were significantly lower after temporary APOLT, rather than those after a standard LDLT, although the operation took longer in the former group. The whole liver volume, including the graft and the remnant native liver, was larger in the temporary APOLT group than in the standard LDLT group, possibly resulting in the improvement in the laboratory data immediately after transplantation.
The rate of complications was comparable between the temporary APOLT group and the standard LDLT group. High incidences of steal syndrome and biliary complications after APOLT have been previously reported (33, 34). Portal blood might easily flow into the remnant native liver when the intraportal pressure is high in the liver graft, such as in cases of acute rejection and anastomotic stenosis of the portal vein. We terminated the portal blood flow to the remnant native liver, resulting in no cases of steal syndrome. Biliary complications may occur as a result of anastomosis between the recipient's left hepatic duct and small-diameter stumps of the graft hepatic duct. No cases of biliary stricture at hepatico-jejunostomy sites or sites of common hepatic duct to hepatic duct anastomosis occurred in the temporary APOLT group. After experiencing three cases of biliary stricture with a left hepatic duct to hepatic duct anastomosis, we began using a common hepatic duct to hepatic duct anastomosis with temporary external biliary drainage from the remnant native liver (24).
APOLT was initially indicated for the treatment of fulminant hepatic failure as a temporary or permanent support to possibly reverse liver failure (12). This procedure for the treatment of fulminant hepatic failure has an advantage in that immunosuppressive therapy can potentially be withdrawn after the recovery of the primary disease (35). Kato et al. recently reported the successful withdrawal of immunosuppressive therapy after native liver regeneration in pediatric patients with fulminant hepatic failure (36). However, the indications for APOLT for the treatment of fulminant hepatic failure remain controversial because this advantage has rarely been achieved and a high incidence of technical complications has been reported (37–39).
The indications for APOLT have been subsequently extended to include cases of other liver diseases in which a small-for-sized graft procured from a living donor must be used (13,40). Inomata et al., however, reported that the remnant native liver functioned unsatisfactorily to support a small-for-sized graft in APOLT for the treatment of end-stage liver disease (41). Kasahara et al. also reported that APOLT should have restricted indications for small-for-sized grafts because of the severe biliary complication and pointed out a likely suitable indication for noncirrhotic metabolic liver disease (34). In this study, we obtained excellent outcomes without severe complications after temporary APOLT for FAP patients using significantly small volume graft. Our data strongly support the concept that temporary APOLT might be suitable for the treatment of FAP patients for whom only an insufficiently sized graft is available.
In temporary APOLT for FAP, the remnant native liver is used as a reservoir until the graft enlarges to a size sufficient to sustain the recipient's life, avoiding liver failure. The remnant liver must be subsequently removed, as it could cause the development of the original disease through the production of abnormal amyloid. Remnant liver resection must be performed after the sufficient enlargement of the graft. The control of blood flow to both the graft and the remnant liver is a key to obtaining the sufficient enlargement of the graft, leading to atrophy of the remnant liver. Therefore, we ligated and divided the right branch of the portal vein to the remnant liver after implanting the graft. In this procedure, the portal blood flow to the remnant liver was maintained until the reperfusion of the liver graft to avoid retention, especially for the intestine, during vessel anastomosis (17). We evaluated the anatomic and functional volume of the graft using CAT scan volumetry and 99mTc-GSA scintigraphy after the temporary APOLT. Sufficient enlargement of the graft to more than 40% of the recipient's SLV was obtained in 12 of the 13 recipients. Six patients experienced pleural effusion requiring invasive intervention. The pleural effusion might have occurred as a result of the remnant liver resection. All six patients recovered after undergoing US-guided thoracentesis. Remnant liver resection was safely performed 2 months after temporary APOLT without any severe surgical complications or the development of FAP symptoms during the interval between the APOLT and the remnant liver resection in all the recipients.
As for a domino transplantation that is another option for expanding the donor pool, we have applied it to both standard LDLT and temporary APOLT, previously reported (16, 42–44). Instead of a whole liver, hemiliver grafts could be transplanted to other patients at the time of both the temporary APOLT and the subsequent remnant liver resection, although this procedure is complicated.
The hospital stay was longer in the temporary APOLT group than in the standard LDLT group because most recipients in the temporary APOLT group remained in the hospital between the temporary APOLT procedure and the subsequent remnant liver resection.
We successfully performed temporary APOLT using small grafts without postoperative liver failure, followed by remnant liver resection, for the treatment of patients with FAP. Sufficient enlargement of the liver graft was obtained about 2 months after APOLT because of the ligation of the portal vein to the remnant liver. Temporary APOLT for FAP recipients might be an alternative procedure to expand the donor pool for LDLT.
Funding sources: We have no funding sources to declare.
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.