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Keywords:

  • Congestion;
  • living-donor transplantation;
  • middle hepatic vein;
  • mitochondrial redox;
  • near-infrared spectroscopy;
  • reconstruction

Abstract

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

Near-infrared spectroscopy (NIRS), which enables non-destructive evaluation of hemoglobin (Hb) oxygenation and the redox state of cytochromeoxidase (Cyt.aa3) in living tissues, has been employed during surgery to detect possible impairment of hemodynamics and mitochondrial respiration in the anterior segment of a right lobe liver graft in living-donor liver transplantation (LDLT). Thirty-six patients undergoing LDLT using a right lobe graft without the middle hepatic vein (MHV) were enrolled in this study. During the course of harvesting and implantation, NIRS measurements were performed on the anterior segments of the liver grafts. In two recipients of liver grafts with Hb residue over 70% in the anterior segment after ex vivo flushing, the MHV tributary was reconstructed, while it was not reconstructed in the other 34 recipients. Of those 34 recipients, 16 recipients of liver graft with 40–70% Hb residue showed transient increase of transaminase levels after LDLT. Of those 16 recipients, six recipients who showed reduction in oxidized Cyt.aa3 in the anterior segment suffered from persistent hyperbilirubinemia after LDLT. In patients showing impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries, reconstruction of the MHV tributaries might have a beneficial effect.


Introduction

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

Living-donor liver transplantation (LDLT) is currently accepted as an important potential source of organs for treatment of children and even adults with end-stage liver disease. In adult-to-adult LDLT using a left lobe graft, however, small-for-size grafts are sometimes insufficient to meet the metabolic demands, resulting in a lower chance of survival. One solution to this problem is to use a right liver graft. Two surgical procedures for harvesting a right lobe have been reported: a right lobectomy with drainage of the right hepatic vein (RHV) alone (1–3) and an extended right lobectomy with both RHV and middle hepatic vein (MHV) drainage (4–6). In the case of the former procedure, which is widely used because it is less invasive for donors, the need for drainage from the MHV tributaries (anterior segment branches) has not yet been established. Venous outflow problems associated with deprivation of the MHV tributaries in LDLT using right lobes are common and are sometimes devastating (7–11). To prevent such venous outflow problems, a reliable method for evaluating the need for drainage from the MHV tributaries should be established.

We previously reported the usefulness of intra-operative near-infrared spectroscopy (NIRS), which enables non-destructive evaluation of hemoglobin (Hb) oxygenation and the redox state of cytochromeoxidase (Cyt.aa3) in living organ tissues (12–17), for evaluating the extent of congestion in the anterior segment of the graft after LDLT using right lobe grafts that do not have the MHV (18). By determining the kinetics of Hb washout of the right hepatic lobe graft with clamping of the MHV tributary during ex vivo perfusion, NIRS enabled prediction of venous outflow problems caused by deprivation of the MHV tributaries before implantation, indicating that this method is useful for determining whether MHV tributaries should be reconstructed. When the graft suffered from severe outflow disturbance associated with deprivation of the MHV tributaries, the region where Hb remained after ex vivo flushing was visible even to the naked eye. However, the difference in the degrees of Hb residue could not be detected by the naked eye. When over 60% of Hb was released from the anterior segment within 180 s after initial flushing, temporary mild or even no remarkable congestion in the anterior segment occurred after surgery. In contrast, when over 70% of Hb remained after ex vivo perfusion in the anterior segment, persistent circulatory impediment causing atrophy of the anterior segment inevitably occurred. Hence, we have decided on our policy that the MHV tributary should be reconstructed in recipients of liver graft with high Hb residue in the anterior segment after ex vivo flushing (over 70%) and have applied this criterion to 36 subsequent patients who underwent LDLT using a right lobe graft without the MHV. Through analysis of those cases, we verified the usefulness of intra-operative NIRS for prediction of venous outflow problems associated with deprivation of the MHV tributaries in LDLT using right lobes.

Patients and Methods

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

Patient population

Thirty-six patients who underwent adult-to-adult LDLT using a right lobe graft without the MHV at Hiroshima University Hospital were enrolled in this study (Table 1). Patients in whom serious complications other than venous outflow problems (e.g. sepsis, acute rejection and bile leakage) occurred within 1 month after LDLT were excluded. The 36 patients included 23 males and 13 females ranging in age from 27 to 68 years (mean ± SD age, 50.3 ± 10.3 years). Graft weight and graft-to-recipient body weight ratio (GRWR) ranged from 482 to 940 g (mean weight, 664.7 ± 130.1 g) and from 0.68% to 1.92% (mean ratio, 1.04 ± 0.26%), respectively. Original diseases of the patients were hepatitis C virus-related cirrhosis in 15 patients (associated with hepatocellular carcinoma in 10 patients), hepatitis B virus-related cirrhosis in 8 patients (associated with hepatocellular carcinoma in 5 patients), fluminant hepatic failure in 5 patients, autoimmune hepatitis in 4 patients, primary biliary cirrhosis in 1 patient and metastatic liver tumor in 1 patient. The graft donors were 22 offsprings, 6 siblings, 2 parents and 1 spouse, with ages ranging from 18 to 61 years (mean age, 33.6 ± 12.7 years). Informed consent for participation in the study was obtained from patients. The study protocol was approved by the Medical Ethics Committee of Hiroshima University.

Table 1. Patient characteristics
CaseRecipientGraft DonorGRWR (%)Size of MHV tributaries (mm)Residual Hb content (%)
AgeGenderDiagnosisMELDAgeGenderRelationshipweight (mL)
  1. M = male; F = female; MELD = model for end-stage liver disease; MHV = middle hepatic vein; PBC = primary biliary cirrhosis; LC = liver cirrhosis; HC = hepatitis C; HB = hepatitis B; AIH = autoimmune hepatitis; HCC = hepatocellular carcinoma; FH = fulminant hepatic failure.

158MLC(HC)27.727FOffspring5560.9<452.1
237FPBC5.836FSibling5660.9<46.5
363MLC(HC), HCC13.329MOffspring7621.2<424.1
450MLC(HC), HCC14.854FSpouse6040.8<422.5
560FLC(HC)20.333MOffspring5800.9<448.7
666FLC(HC), HCC16.737FOffspring6720.952.8
757MLC(HC), HCC7.029MOffspring6021.1759.2
827MAIH35.728MSibling7081.1765.7
962MLC(HB), HCC12.028MOffspring8561.0>782.9
1040MFH24.542FSibling6960.8626.5
1159FFH30.129MOffspring9401.5436.2
1248FAIH30.453MSibling9021.7561.4
1352MLC(HC)11.822MOffspring7420.9563.7
1457MLC(HB), HCC9.232FOffspring5660.7666.1
1558MLC(alcholic)16.726MOffspring7101.0429.7
1656MFH34.628FOffspring5480.960.3
1749MLC(HC), HCC18.921MOffspring5500.8449.3
1860MLC(HC), HCC10.424MOffspring5641.0426.2
1954MLC(HB), HCC13.320MOffspring8961.4422.3
2055FLC(HC), HCC10.960MSibling5260.9541.7
2150MLC(HB), HCC27.020MOffspring8841.2631.5
2229MLC(HC)20.161MParent5361.4519.0
2347MLC(HC), HCC10.620MOffspring6321.0321.9
2443MLC(HB), HCC35.257FSpouse6781.0236.9
2528MLiver metastasis6.057FParent4940.8<454.3
2656MFH43.926MOffspring6140.9<416.5
2758MLC(HB)29.430MOffspring5500.960.0
2844FAIH18.149FSibling6601.2539.4
2946FLC(HB)23.418FOffspring4820.8<425.7
3068FLC(HC)20.743FOffspring6180.9<451.0
3157MLC(HC), HCC19.130MOffspring6300.9559.5
3250FAIH44.129MOffspring7140.94.26.4
3320FFH29.043FParent5380.9462.6
3458MLC(HC), HCC16.929MOffspring9001.1>755.3
3557FLC(HB), HCC3.118MOffspring6301.25.558.1
3650FLC(alcholic)20.722MOffspring8241.9>773.8

Surgical technique

Donor hepatectomy and the recipient transplantation procedure were performed as described previously (18). In brief, the right lobe, without the MHV, was harvested from the donor as follows. An intra-operative ultrasonographic (US) examination was performed for final identification of the anatomy of the hepatic veins and portal veins (PV). Parenchymal transection was performed on the right side of the gallbladder fossa. During parenchymal transection, major right tributaries of the MHV draining from the anterior segment were clamped using a vascular clip and transected. After hepa- tectomy, ex vivo perfusion of the right lobe graft was performed through the PV. The initial perfusate was saline solution (500 mL) followed by the University of Wisconsin solution (1000 mL). During initial perfusion, real-time and continuous NIRS measurement was performed on the anterior segment of the right lobe graft to determine the kinetics of Hb washout from the hepatic tissue as described later.

For the recipient, the implantation was performed after total hepatectomy. The middle and left hepatic veins were closed, and then the graft RHV was anastomosed to the RHV of the recipient in an end-to-end fashion. When indicated, the MHV tributary was reconstructed by use of the recipient's external iliac vein as an interposition or by directly anastomosing to the recipient's MHV trunk. After end-to-end anastomosis of the graft right PV to the PV of the recipient, the graft was reperfused before microsurgical reconstruction of the hepatic artery (HA) (end-to-end anastomosis of the HA of the graft to the right or left HA of the recipient). The bile duct of the graft liver was anastomosed in an end-to-end fashion to the common or right hepatic bile duct of the recipient. All recipients continuously received i.v. injection of prostaglandin E1 (PGE1) (0.01 μg/kg/min) during surgery and for 24 h after surgery. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and serum bilirubin were measured as indexes of liver function. The initial immunosuppressive regimen consisted of tacrolimus and steroids. Computed tomography (CT) scans and Doppler US were routinely performed.

Intra-operative NIRS

During the course of harvesting and implantation, in vivo NIRS measurements were performed on the anterior segments of the liver grafts to determine Hb and Cyt.aa3 contents in the hepatic tissues as indicators of congestion and redox state. For these measurements, multi-point (2–3 points) scanning was performed, and data were averaged to quantitatively evaluate the state of venous congestion in the whole anterior segment. In addition, during initial ex vivo perfusion, continuous NIRS measurement was performed on the anterior segment of the right lobe graft to determine the kinetics of Hb washout from the hepatic tissue. The center point of the right paramedian sector was serially scanned every 30 s for at least 180 s. Since tissue Hb contents incessantly altered during ex vivo perfusion, such measurements did not allow multiple-point scanning. For fear of a detached endothelium of the HA, ex vivo HA perfusion was not performed in any cases of the present series. Probably because of intra-hepatic communication between the PV and HA, most (but not all) of Hb was washed out by ex vivo perfusion via the PV if outflow disturbance did not occur. NIRS measurement was carried out as follows. NIR reflectance was measured with a multichannel photodetector (MCPD-2000, Otsuka Electronics, Osaka, Japan) connected to a personal computer (PC-9801FS, NEC, Tokyo, Japan). NIR light from a halogen lamp at 300 W was directed through a flexible bundle of quartz optical fibers to the liver, and the reflected light was conveyed through another bundle to a spectrophotometer. The tips of the two fiber bundles were fixed at a position approximately 1 cm above the liver, and the distance between the two probes was approximately 1 cm. The reflected light was measured sequentially in the range of 700–1000 nm with an interval of 2 nm. The sampling time for each scan was 4 s. The difference between the spectrum from the liver immediately after laparotomy of the donor and that from the liver shortly before closure of the recipient's abdomen and the difference between the spectrum from the liver just before initial ex vivo perfusion and that from the liver during ex vivo perfusion were calculated, i.e. the difference in the gross optical densities between them was calculated at 2 nm wavelength intervals to obtain the ‘subtracted spectrum’ (16,19). Following Beer-Lambert law (12), then multi-component analysis of the subtracted spectrum was performed by use of least-square curve-fitting on the basis of singular value decomposition to quantify the changes in each component (20). The five components were fitted with the following equation:

  • image

where OD(λ), L(λ) and e1–5(λ) are optical density, mean light path length and extinction coefficient of each component at a wavelength of λ, respectively. The changes in Hb contents were calculated by adding the changes in oxy-Hb and deoxy-Hb. Hb residue in the anterior segment of the liver graft after ex vivo perfusion was represented by percentage of total change in Hb content in the posterior segment (18). The whole process of this analysis took about 10 min.

Statistical analysis

Statistical analysis was performed using Student's t-test. Multivariate analysis was performed using factor analysis. Survival curves were estimated by the Kaplan-Meier method and compared with log-rank test. Differences at p < 0.05 were considered significant.

Results

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

Patients

In two of the 36 cases, over 70% of Hb remained in the anterior segment even after ex vivo perfusion. In those recipients of liver grafts with high Hb residue, the MHV tributary was reconstructed in accordance with our policy (high Hb residue group). In the other 34 recipients of liver grafts with Hb residue of less than 70% in the anterior segment after ex vivo flushing, the MHV tributary was not reconstructed. Those 34 recipients were divided into two groups according to the percentage of remaining Hb content in the anterior segment of the graft liver after ex vivo flushing: 16 recipients of liver grafts with 40–70% Hb residue (intermediate Hb residue group) and 18 recipients of liver grafts with Hb residue of less than 40% (low Hb residue group). We found in our previous study that Cyt.aa3 redox was preserved in all recipients of liver grafts with Hb residue of less than 40%, whereas all recipients of liver grafts with Hb residue over 70% showed reduction in oxidized Cyt.aa3 in the anterior segment (18).

Reconstruction of the MHV tributary prevented anterior segment congestion in recipients of liver grafts with high Hb residue afterex vivoflushing

In the two patients in the high Hb residue group, the MHV tributary was reconstructed by use of the recipient's external iliac vein as an interposition or by directly anastomosing to the recipient's MHV trunk. In this study, we demonstrated that the extent of post-operative congestion (ΔHb: change in tissue Hb before harvesting and after implantation) in the anterior segment was significantly correlated with the tissue content of remaining Hb in that segment after ex vivo perfusion (at 180 s after initial flushing). By reconstruction of the MHV tributary, the extent of post-operative congestion was markedly relieved in both patients in the high Hb residue group compared with the expected extent of post-operative congestion without reconstruction (Figure 1). Those two patients showed no remarkable elevation of liver function indexes, i.e. serum levels of AST, ALT and bilirubin, after LDLT (data not shown). Thus, reconstruction of the MHV tributary lessened anterior segment congestion in recipients in the high Hb residue group.

image

Figure 1. Relationship between the remaining Hb content after initial flushing and the extent of post-operative congestion in the anterior segment. During initial ex vivo perfusion, continuous NIRS measurement was performed on the anterior segment of the right lobe graft with clamping the MHV tributaries to determine the kinetics of Hb washout from the hepatic tissue. The extent of post-operative congestion (ΔHb) in the anterior segment was significantly correlated with the tissue content of remaining Hb in that segment after ex vivo perfusion (at 180 s after initial flushing). Open circles are data from a patient in our previous study. Closed squares and triangles are data from patients of liver grafts with high Hb residue in the present study. By reconstruction of the MHV tributaries, the extent of post-operative congestion was markedly relieved.

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Mild congestion in the anterior segment caused by deprivation of the MHV tributaries led to transient increase of transaminase levels after LDLT

Figure 2 shows the kinetics of serum transaminase levels in the recipients of liver grafts with Hb residue of less than 70% in the anterior segment after ex vivo flushing, in whom the MHV tributaries were not reconstructed. Although, the peak values of transaminases did not differ among those patients during the initial phase, the levels of transaminases in intermediate Hb residue group recipients were transiently but significantly elevated at 2–3 weeks after transplantation. Spontaneous improvement of the transaminase levels might be due to growth of intra-hepatic collaterals between the MHV tributaries and the RHV. In contrast, such an increase of transaminase levels was not observed in low Hb residue group recipients. We performed multivariate analyses to determine factors relevant to elevation of transaminases after LDLT. By factors analyses, no significant risk factors other than congestion in the anterior segment for elevation of serum transaminase levels were determined in the present series (data not shown). In addition, there was no difference between the intermediate Hb residue group and low Hb residue group in any of the pre-operative laboratory data, model for end-stage liver disease (MELD) score, graft volume and GRWR ratio (Table 2). These findings indicate that the differences in transaminases between groups are not due to either the small for size syndrome or pre-operative condition of recipients. Thus, mild congestion in the anterior segment caused by deprivation of the MHV tributaries leads to transient liver dysfunction.

image

Figure 2. Kinetics of serum aspartate aminotransferase (AST) levels (A) and alanine aminotransferase (ALT) levels (B) in recipients of liver grafts with 40–70% Hb residue (intermediate Hb residue group, n = 16) and recipients of liver grafts with Hb residue of less than 40% (low Hb residue group, n = 18). Average +/− SD for the individual groups are shown. p < 0.01 between groups.

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Table 2. Clinical parameters in the recipients of liver grafts with Hb residue of less than 70% in the anterior segment
 Low Hb residue group (n = 18)Intermediate Hb residue group (n = 16)p-Values
  1. Average values ± SD (range) for the individual groups are shown.

  2. M = male; F = female; MELD = model for end-stage liver disease; AST = aspartate aminotransferase; ALT = alanine aminotransferase; GRWR = graft to recipient body weight ratio.

Recipient age (year)51.4 ± 9.4 (29–66)49.7 ± 13.8 (20–68)0.61
Recipient gender (M/F)12/610/6 
MELD22.8 ± 11.7 (6–44)18.2 ± 9.9 (3–36)0.23
Pre-operative T-Bil11.1 ±10.0 (1.3–28.8)7.6 ± 9.0 (0.6–25.0)0.48
Pre-operative AST217.4 ± 620.4357.1 ± 959.60.64
Pre-operative ALT148.2 ± 410.6264.9 ± 773.10.87
Donor age (year)32.9 ± 13.5 (18–57)35.4 ±12.9 (18–60)0.56
Donor gender (M/F)11/710/6 
Graft weight (g)667.3 ± 131.8 (482–940)639.9 ± 122.6 (494–902)0.54
GRWR1.05 ± 0.21 (0.82–1.42)0.97 ± 0.23 (0.68–1.24)0.34
Total ischemic time (min)107.9 ± 31.6 (198–72)91.8 ± 38.2 (193–47)0.19

Impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries leads to the hyperbilirubinemia after LDLT

Figure 3A shows the kinetics of serum levels of total bilirubin in the recipients of liver graft with Hb residue of less than 70% in the anterior segment after ex vivo flushing. The intermediate Hb residue group included some patients showing persistent elevation of total bilirubin levels, whereas no patients in the low Hb residue group showed such persistent hyperbilirubinemia. We attempted to determine the NIRS parameters that can predict such persistent hyperbilirubinemia. Since the energy required for bile formation is provided by mitochondrial respiration in hepatocytes, impairment of mitochondrial redox may lead to hyperbilirubinemia. Since Cyt.aa3 is the terminal member of the mitochondrial respiratory chain and its redox state changes in response to oxygen availability at the cellular level, a decrease in oxidized Cyt.aa3 content in liver tissue should be an indicator of impairment of mitochondrial respiration. Hence, the 16 patients in the intermediate Hb residue group were further divided into two groups according to the change in oxidized Cyt.aa3 content in the anterior segment liver tissues before harvesting and after implantation. We previously reported that mild congestion in the anterior segment of a right lobe liver graft reflected an increase in oxy-Hb rather than that in deoxy-Hb (18). In that series, no reduction of oxidized Cyt.aa3 content was seen in the anterior segment in the majority of patients showing mild congestion in the anterior segment. In the present series, no patients in the low Hb residue group showed reduction in oxidized Cyt.aa3 in the anterior segment, indicating a well-preserved mitochondrial redox state (data not shown). In contrast, 6 patients in the intermediate Hb residue group showed reduction in oxidized Cyt.aa3 in the anterior segment of the liver graft after LDLT. In the patients showing reduced tissue content of oxidized Cyt.aa3, serum levels of total bilirubin were significantly higher than those in patients in the intermediate Hb residue group who showed well-maintained tissue content of oxidized Cyt.aa3 in the anterior segment (Figure 3B). Notably, the survival of grafts showing reduced tissue content of oxidized Cyt.aa3 was significantly worse than those of grafts showing well-maintained oxidized Cyt.aa3 content in the low and intermediate Hb residue groups, indicating the impact of mitochondrial redox impairment in the anterior segment on the graft outcome (Figure 4). In the present series, all donor livers were completely normal, ruling out the possibility of either fat infiltration or fibrosis, etc. There was no relationship between results of NIRS measurements and donor age. In addition, there was no relationship between donor age and serum levels of total bilirubin, transaminase levels or graft survivals after LDLT. Between patients showing reduced tissue content of oxidized Cyt.aa3 and patients showing well-maintained levels, there was no difference in any of pre-operative laboratory data, MELD score, graft volume and GRWR ratio (Table 3). Thus, in patients showing impairment of mitochondrial redox associated with congestion caused by deprivation of the MHV tributaries, reconstruction of the MHV tributaries might have a beneficial effect for preventing hyperbilirubinemia after LDLT.

image

Figure 3. Kinetics of total bilirubin in recipients of liver grafts with 40–70% Hb residue (intermediate Hb residue group, n = 16) and recipients of liver grafts with Hb residue of less than 40% (low Hb residue group, n = 18) (A). The patients in the intermediate Hb residue group were further divided into two groups according to the change in oxidized Cyt.aa3 content in the anterior segment liver tissues before harvesting and after implantation. In the patients showing reduced tissue content of oxidized Cyt.aa3 (n = 6), serum levels of total bilirubin were significantly higher than those in patients in the intermediate Hb residue group who showed well-maintained tissue content of oxidized Cyt.aa3 in the anterior segment (n = 10) (B). Average +/− SD for the individual groups are shown. *p < 0.05 between groups.

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image

Figure 4. The survival curves of liver grafts with 40–70% Hb residue (intermediate Hb residue group, n = 16) and recipients of liver grafts with Hb residue of less than 40% (low Hb residue group, n = 18, indicated by solid line). The patients in the intermediate Hb residue group were further divided into two groups according to the change in oxidized Cyt.aa3 content in the anterior segment liver tissues before harvesting and after implantation. In the patients showing reduced tissue content of oxidized Cyt.aa3 (n = 6, indicated by broken line), the graft survival was significantly worse than that in patients in the intermediate Hb residue group who showed well-maintained tissue content of oxidized Cyt.aa3 in the anterior segment (n = 10, indicated by dotted line). *p < 0.05, log-rank test.

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Table 3. Clinical parameters in the intermediate Hb residue group
 Intermediate Hb residue group (n = 16)p-Values
Well-maintained Cyt.aa3 (n = 10)Reduced oxidized Cyt.aa3 (n = 6)
  1. Average values ± SD (range) for the individual groups are shown.

  2. M = male; F = female; MELD = model for end-stage liver disease; AST = aspartate aminotransferase; ALT = alanine aminotransferase; GRWR = graft to recipient body weight ratio.

Recipient age (year)53.1 ± 10.8 (27–68)40.4 ± 16.6 (20–58)0.17
Recipient gender (M/F)5/55/1 
MELD17.8 ± 9.8 (3–36)17.1 ± 10.2 (6–29)0.83
Pre-operative T-Bil7.5 ±8.7 (0.6–23.1)11.3 ± 12.7 (0.8–27.6)0.64
Pre-operative AST590.3 ± 1237.1294.6 ± 292.30.54
Pre-operative ALT461.6 ± 1000.1325.8 ± 421.70.68
Donor age (year)33.9 ± 14.0 (18–60)40.2 ± 11.6 (27–57)0.55
Donor gender (M/F)8/23/3 
Graft weight (g)672.2 ± 138.1 (526–906)592.0 ± 72.1 (494–696)0.54
GRWR1.02 ± 0.29 (0.68–1.67)0.90 ± 0.10 (0.75–1.06)0.18
Total ischemic time (min)104.9 ± 42.7 (48–193)68.0 ± 20.0 (47–93)0.11

Discussion

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

Although poor venous outflow can result in engorgement and graft failure after LDLT (10,11), many authors have reported that right liver grafts showed good function without reconstruction of the MHV tributaries (2,3,8,21,22). One possible explanation for such good results is that drainage flow from the anterior segment to the posterior segment of a right lobe graft is established by means of intra-hepatic PV and then into the RHV (23). Another possible explanation is that intra-hepatic communication between the MHV tributaries and the RHV contributes to the prevention of congestion of the anterior segment (24). If such vein communications are significant in a right lobe graft, reconstruction of the MHV tributaries might not be required for adequate hepatic venous drainage. The necessity for reconstruction of MHV tributaries or the inferior RHV is currently judged by the caliber of such vessels (2,10). Information on the presence or absence of hepatic segmental congestion after temporarily clamping the corresponding vein during donor surgery is also useful (8). Previous studies have demonstrated that concomitant temporary clamping of the HA is also useful for diagnosis of venous congestion of the liver, because the hepatofugal area is discolored under these conditions (9,25). Using this method, hepatic venous congestion in the anterior segment of right lobe was routinely investigated intraoperatively after parenchyma transection in the present series. When the graft suffered from severe outflow disturbance caused by simultaneous clamping of MHV tributaries and the right HA, liver surface discoloration was visible to the naked eye. Intra-operative Doppler US was also performed after declamping of only the HA. If the portal flow of the anterior segment was hepatofugal, the area was confirmed to be congestive. However, we could not detect differences in the degrees of congestion by the naked eye.

As a more objective method for predicting hepatic vein drainage problems, we have used NIRS, which enables nondestructive and continuous evaluation of Hb and Cyt.aa3 contents in living organ tissues (18). NIRS measurement enabled accurate prediction of hepatic hemostasis caused by deprivation of the MHV tributaries, indicating that this method is useful for determining whether MHV tributaries should be reconstructed. Recipients of liver grafts with high Hb residue (over 70%) even after ex vivo flushing who showed impairment of mitochondrial respiration were considered to be appropriate candidates for reconstruction of MHV tributaries, since those patients inevitably suffered from significant increase in serum transaminase levels after LDLT if reconstruction of MHV tributaries was not done. Based on the results of our previous study, the MHV tributaries in the two patients in the high Hb residue group in the present series were reconstructed by use of the recipient's external iliac vein as an interposition or by directly anastomosing to the recipient's MHV trunk.

The possible influence of systemic hemodynamics on in vivo NIRS measurements might be taken into account. Congestion of a liver graft does not only result from venous outflow insufficiency but might also be exacerbated by portal hypertension. Particularly in cases with marginal communicating veins, portal pressure after grafting might be an important factor for deciding whether to reconstruct MHV tributaries in a right liver graft. Since the present series, in which portal pressure after the LDLT (at the end of recipient surgery) was between 15 and 20 mmHg in all cases (data not shown), did not allow us to analyze this issue, further studies are needed. In addition to portal pressure, central venous pressure also might influence the results of in vivo NIRS measurements. However, central venous pressure was less than 10 mmHg during recipient surgery in almost all cases (data not shown), and it is therefore unlikely that central venous pressure influenced the results in the present series. Nevertheless, it seems difficult to evaluate only venous outflow problems in vivo, because hepatic hemodynamics is complexly influenced by inflow (portal/HA blood supply), sinusoidal microcirculation and hepatic vein outflow. NIRS measurement of remaining tissue Hb during ex vivo flushing probably has the advantage of minimizing effects of factors other than venous outflow.

In our previous study, recipients of liver grafts with high Hb residue in whom reconstruction of the MHV was not performed showed significant impairment of mitochondrial respiration as indicated by decreased oxidized Cyt.aa3 content in the anterior segment after implantation (18). Such impairment of mitochondrial redox in the liver graft should be associated with disadvantages in post-operative liver volume regeneration. In the present study, we demonstrated that impairment of mitochondrial redox associated with congestion in the anterior segment of a liver graft leads to hyperbilirubinemia after LDLT. This finding is intelligible, since the energy required for bile formation is provided by mitochondrial respiration in hepatocytes. Alteration of Cyt.aa3 redox in the anterior segment of a liver graft obtained through NIRS measurement would also be a useful parameter to determine indication for reconstruction of the MHV tributaries. The degree of hyperbilrubinemia might be related to the amount of graft with well-preserved perfusion relative to the body weight of the recipient. However, a method to quantify the amount of graft with good perfusion has not been established so far. Instead of evaluating graft volume with good perfusion, we comprehensively evaluated graft volume with poor perfusion and extent of outflow disturbance by NIRS in the present series of adult-to-adult LDLT showing relatively narrow variation in GRWR. Since small-for-size grafts are likely to be susceptible to graft dysfunction caused by outflow disturbance, further efforts to address the reciprocal relevance among graft volume, congestion of the anterior segment and post-operative hyperbilrubinemia might be needed.

When NIRS is applied to living tissues, the ‘field of view’ of scanning should be taken into account. It has been established that the ‘mean light pathlength,’ labeled ‘field of view,’ in in vivo NIRS is 4- to 6-fold greater than the distance between the transmitting and receiving optical bundles when those are vertically applied to the scanned tissues and the intensity of the light source is adequate (26). In our NIRS system, the distance between the transmitting and receiving optical bundles was 1 cm; thus, the NIRS provides changes in tissue content of Hb per unit area in a hemisphere around a receiving optical probe with a radius of 4–6 cm (mean light pathlength) (i.e. the spectrophotometric view = 25–55 cm3). This suggests that several-point scanning might be sufficient to quantitatively represent the state of venous congestion in a subsegment of the liver graft. However, this method did not enable accurate determination of the venocongestive areas in the liver grafts. To compensate for this defect, visualization of the venocongestive area by temporary clamping of the corresponding vein and the HA during donor surgery (25) would be helpful.

In conclusion, intra-operative NIRS enabled quantification of the extent of congestion and the influence of the oxygenation state of right lobe liver grafts by determining changes in tissue contents of oxy-Hb, deoxy-Hb, oxidized and reduced Cyt.aa3.

Acknowledgments

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

The authors thank Drs. Takashi Onoe, Kohei Ishiyama, Kentaro Ide, Masayuki Shishida, Masahiro Ohira, Yuka Tanaka and Kazuyuki Mizunuma for their advice and encouragement.

This work was supported by Grant-in-Aid for Scientific Research (B) (16390364), (C) (17500329) from the Japan Society for the Promotion of Science.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  • 1
    Yamaoka Y, Washida M, HoNnda K et al. Liver transplantation using a right lobe graft from a living related donor. Transplantation 1994; 57: 11271130.
  • 2
    Inomata Y, Uemoto S, Asonuma K, Egawa H. Right lobe graft in living donor liver transplantation. Transplantation 2000; 69: 258264.
  • 3
    Grewal HP, Shokouh-Amiri MH, Vera S, Stratta R, Bagous W, Gaber AO. Surgical technique for right lobe adult living donor liver transplantation without venovenous bypass or portocaval shunting and with duct-to-duct biliary reconstruction. Ann Surg 2001; 233: 502508.
  • 4
    Lo CM, Fan ST, Liu CL et al. Extending the limit on the size of adult recipient in living donor liver transplantation using extended right lobe graft. Transplantation 1997; 63: 15241528.
  • 5
    Fan ST, Lo CM, Liu CL, Yong BH, Chan JK, Ng IO. Safety of donors in live donor liver transplantation using right lobe grafts. Arch Surg 2000; 135: 336340.
  • 6
    Fan ST, Lo CM, Liu CL. Technical refinement in adult-to-adult living donor liver transplantation using right lobe graft. Ann Surg 2000; 231: 126131.
  • 7
    Kaneko T, Kaneko K, Sugimoto H et al. Intrahepatic anastomosis formation between the hepatic veins in the graft liver of the living related liver transplantation: Observation by Doppler ultrasonography. Transplantation 2000; 70: 982985.
  • 8
    Cui D, Kiuchi T, Egawa H et al. Microcirculatory changes in right lobe grafts in living-donor liver transplantation: A near-infrared spectrometry study. Transplantation 2001; 72: 291295.
  • 9
    Cescon M, Sugawara Y, Sano K, Ohkubo T, Kaneko J, Makuuchi M. Right liver graft without middle hepatic vein reconstruction from a living donor. Transplantation 2002; 73: 11641166.
  • 10
    Ghobrial RM, Hsieh CB, Lerner S et al. Technical challenges of hepatic venous outflow reconstruction in right lobe adult living donor liver transplantation. Liver Transpl 2001; 7: 551555.
  • 11
    Lee S, Park K, Hwang S et al. Congestion of right liver graft in living donor liver transplantation. Transplantation 2001; 71: 812814.
  • 12
    Jobsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 1977; 198: 12641267.
  • 13
    Wyatt JS, Cope M, Delpy DT, Wray S, Reynolds EO. Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry. Lancet 1986; 2: 10631066.
  • 14
    Tashiro H, Suzuki S, Kanashiro M et al. A new method for determining graft function after liver transplantation by near-infrared spectroscopy. Transplantation 1993; 56: 12611263.
  • 15
    Ohdan H, Fukuda Y, Suzuki S, Amemiya H, Dohi K. Simultaneous evaluation of nitric oxide synthesis and tissue oxygenation in rat liver allograft rejection using near-infrared spectroscopy. Transplantation 1995; 60: 530535.
  • 16
    Noriyuki T, Ohdan H, Yoshioka S, Miyata Y, Asahara T, Dohi K. Near-infrared spectroscopic method for assessing the tissue oxygenation state of living lung. Am J Respir Crit Care Med 1997; 156: 16561661.
  • 17
    El-Desoky AE, Delpy DT, Davidson BR, Seifalian AM. Assessment of hepatic ischaemia reperfusion injury by measuring intracellular tissue oxygenation using near infrared spectroscopy. Liver 2001; 21: 3744.
  • 18
    Ohdan H, Mizunuma K, Tashiro H et al. Intraoperative near-infrared spectroscopy for evaluating hepatic venous outflow in living-donor right lobe liver. Transplantation 2003; 76: 791797.
  • 19
    Shibata S, Ohdan H, Noriyuki T, Yoshioka S, Asahara T, Dohi K. Novel assessment of acute lung injury by in vivo near-infrared spectroscopy. Am J Respir Crit Care Med 1999; 160: 317323.
  • 20
    Press WH, Teukolsky SA, Vetterling WT, Flannery BP. Singular value decomposition. In: Numerical Recipes in C: The Art of Scientific Computing, 2nd Ed. New York : Cambridge University Press, 1992: 5970.
  • 21
    Marcos A, Fisher RA, Ham JM et al. Right lobe living donor liver transplantation. Transplantation 1999; 68: 798803.
  • 22
    Marcos A, Ham JM, Fisher RA, Olzinski AT, Posner MP. Surgical management of anatomical variations of the right lobe in living donor liver transplantation. Ann Surg 2000; 231: 824831.
  • 23
    Deutsch V, Rosenthal T, Adar R, Mozes M. Budd-Chiari syndrome. Study of angiographic findings and remarks on etiology. Am J Roentgenol Radium Ther Nucl Med 1972; 116: 430439.
  • 24
    Maguire R, Doppman JL. Angiographic abnormalities in partial Budd-Chiari syndrome. Radiology 1977; 122: 629635.
  • 25
    Sano K, Makuuchi M, Miki K et al. Evaluation of hepatic venous congestion: Proposed indication criteria for hepatic vein reconstruction. Ann Surg 2002; 236: 241247.
  • 26
    Van Der Zee P, Cope M, Arridge SR et al. Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing. Adv Exp Med Biol 1992; 316: 143153.