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Background: We investigated the long-term profiles of liver regeneration after living-donor hepatectomy., Methods: Thirty-three donors participated in the study. Preoperative and postoperative liver volume was calculated using computed tomography. Volume assessment was repeated at 1 week, 2 weeks, 1 month, 3 months, 6 months, 12 months, and 4 years postoperatively., Results: Donors were divided into the right (n = 23; residual liver volume, 42%) and left (n = 10; residual liver volume, 63%) groups according to the operative procedures. The restoration ratio to the preoperative liver volume (right vs. left groups) were 51%, 57%, 64%, 74%, 77%, 81%, and 88% vs. 69%, 72%, 76%, 79%, 83%, 84%, and 91% at 1 week, 2 weeks, 1 month, 3 months, 6 months, 12 months, and 4 years, respectively; the interindividual variation in the restoration ratio to the preoperative liver volume became narrower with time., Conclusion: Liver resection in humans resulted in rapid regeneration during the first 3 months, followed by a more moderate rate of regeneration thereafter, in proportion to the amount of liver mass resected. The volume of the regenerating liver appeared to converge towards the individual preoperative volume with time. However, the liver volume was not restored to the preoperative volume at 4 years after the resection.

Background: The relationship among bile duct (BD), portal vein (PV), and/or hepatic artery (HA) anatomy is controversial, but no investigation has previously compared left and right liver graft transplantation in terms of variant vasculobiliary anatomy. Therefore, in this study, we explored whether variant BD anatomy can be predicted from portal PV or HA anatomy, and we compared left and right liver graft transplantation from the standpoint of vasculobiliary reconstruction., Methods: The associations between BD and PV and/or HA anatomies were evaluated in 361 donors. The number of vasculobiliary stumps in each graft, the number of stumps reconstructed, and the clinical outcomes were then compared between 133 left and 154 right liver grafts., Results: Variant BD was more frequently associated with variant than with normal PV anatomy (57.0% vs 28.4%). No correlation was found between variant BD and variant HA anatomy. Multiple PVs (left versus right, 0% vs 5.8%) and BDs (40.6% vs 59.7%) appeared more frequently in right liver grafts, and all stumps were reconstructed. Although multiple HAs appeared more frequently in left liver grafts (47.4% vs 1.3%), multiple stumps were rarely anastomosed. The incidence of HA/PV thrombosis or biliary strictures was comparable between left and right liver grafts., Conclusion: Variant PV, but not variant HA, anatomies frequently accompany variant BD anatomy. Vasculobiliary variations sometimes lead to technical complexities, but this is more problematic in right liver graft transplantation. Left liver grafts are more feasible for vasculo-biliary reconstruction., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Differentiating between acute cellular rejection (ACR) and recurrent hepatitis C virus after liver transplantation in hepatitis C virus-positive patients is difficult, but vital for preventing graft loss., Methods: The blood eosinophil counts 3 days before or on the day of biopsy were retrospectively reviewed to evaluate their value for predicting ACR in 91 biopsy samples from 45 patients., Results: Eosinophil counts on the day of biopsy were significantly higher in the ACR group (n = 20) than in the non-ACR (n = 71) group, although the difference was negligible 3 days before the biopsy. A relative eosinophil count of 2% or an absolute eosinophil count of 200 cells/mm(3) predicted ACR with a specificity of 94% or 96%, respectively., Conclusions: Blood eosinophil count on the day of biopsy can be helpful in the diagnosis of ACR in patients who underwent living donor liver transplantation for hepatitis C virus-related cirrhosis.

Background: An accurate estimation of preoperative volumetric measurements of the donor liver is essential in living donor liver transplantation., Methods: Three-dimensional (3-D) computed tomography (CT) was applied to 56 living donors. 3-D images of the liver were constructed using the region-growing method and the volume of each sector was measured., Results: The median volume ratios of the left liver, caudate lobe, right paramedian, and lateral sectors were 34%, 4%, 38%, and 25% of the total liver volume, respectively. The shape of the congestive area in the right paramedian sector was properly demonstrated by 3-D CT. The volume of the region corresponded to 32% of the right liver. The actual volume of the graft correlated well with the estimated graft volume (n = .86)., Conclusions: The region-growing method was useful for graft selection and for determining the indication of middle hepatic vein reconstruction in right liver grafts.

The lack of consensus on how to evaluate surgical complications of donors in live donor liver transplantation (LDLT) and incoherence of cumulative data hampers efficient comparison of the outcome worldwide. We considered that the application of the internationally validated classification system introduced by Clavien in 2004 might be beneficial. Operative complications of 243 patients who underwent live donor hepatectomy for adult LDLT between January 1996 and October 2005 at the University of Tokyo were analyzed according to the system. Definitions for each grade in the system are: grade I, deviation from the normal postoperative course but without the need for therapy; grade II, complication requiring pharmacologic treatment; grade III, complication with the need for surgical, endoscopic or radiological intervention (IIIa/b: without/with the need for general anesthesia); grade IV, life-threatening complication requiring intensive care; grade V, death. Surgical morbidity was recognized in 67 donors (28%). No deaths occurred. The numbers of patients with complications were: grade I, 36 (15%); II, 10 (4%); IIIa, 12 (5%); IIIb, 9 (4%); IV, 0; V, 0. Six in IIIb underwent surgical repair for bile leakage. Clavien's system is simple and informative. It may serve as a common tool for the quality assessment in live liver donor surgery worldwide, and we propose its application whenever surgical complication of live donor is discussed.

Background: Standard liver volume (SLV) is an important concept in adult living liver donor transplantation. The purpose of this study was to re-evaluate and modify the authors' previous formula for predicting total liver volume (TLV)., Methods: The TLV of 301 Japanese living donors was measured by computed tomography. This TLV was then compared with the liver volume calculated using established formulas. The correlation between TLV and several factors including body surface area (BSA) were analyzed and a new equation (SLVn) to better approximate TLV was determined. Factors related to the difference between TLV and SLVn were examined., Results: Average TLV was 1196.3 +/- 221.0 cm3. Urata's formula underestimated TLV by 17.6 cm3 and the other formulas overestimated it by 120.4-244.9 cm3. TLV could be approximated by BSA; SLVn (cm3) = -404.8 + 961.3 x BSA (m2, R2 = 0.58). SLVn tended to overestimate the TLV of older donors and to underestimate TLV of thin donors., Conclusions: A new simple formula is presented that might be a better fit for calculating TLV in Japanese adults. This formula might be useful for evaluating the size of an adequate graft.

Hepatocellular carcinoma (HCC) nodules newly found in the explant liver have been observed, but the impact on patient prognosis is not known. Sixty HCC patients who underwent living donor liver transplantation were the subjects of the study. Radiologic findings prior to transplantation and pathologic findings of the explant liver were compared. Histologic characteristics of preoperatively overlooked tumors were examined. The influence of the discrepancy between these findings on tumor recurrence was evaluated. A total of 227 HCC nodules were found in the explant livers. Of these, 91 nodules (40%) were newly found by pathologic examination. They were smaller and more likely to be well differentiated than the others. The number and size of the tumors were underestimated in 50% (30/60) and 32% (19/60), respectively. There was no significant difference in the recurrence-free survival rate between patients who met the Milan criteria both in the pre- and post-transplant evaluation (n = 29) and those who met the Milan criteria preoperatively, but exceeded the criteria in the explant (n = 19). Nodules newly found in the explant liver had little impact on recurrence-free survival. A decision for liver transplantation according to the Milan criteria based on preoperative evaluation is valuable for securing an excellent outcome.

Liver transplantation with liver grafts from deceased donors is the treatment of choice for patients suffering from Wilson's disease (WD) with end-stage liver disease. There are few reports, however, on the use of liver grafts from living-related donors for WD. Five (two pediatric and three adult recipients) underwent living-related liver transplantation (LRLT) for WD at the University of Tokyo. Two patients presented with fulminant hepatic failure with hemolysis, and the other three presented with decompensating cirrhosis, one with an overlapping neurologic WD. All recipients had a low serum ceruloplasmin level (median: 18 mg/dL), high urinary copper level (mean: 1119 microg/d), and presented with Kayser-Fleischer rings before transplantation. Although one patient died from early graft thrombosis unrelated to WD, the other four patients have shown an excellent long-term prognosis. Following successful transplantation, there was a significant reduction in urinary copper excretion (median: 64 microg/d) in all patients. The neurologic symptoms of WD in one patient, however, worsened after 2 months and gradually subsided, but not completely, over the 2-yr follow-up. For advanced liver failure in WD, we consider LRLT a valuable life-saving option. The improvement of neurologic symptoms, however, requires further evaluation.

Background: Thrombotic microangiopathy (TMA) is a fatal complication characterized by microvascular occlusive disorder resulting in systemic or intrarenal platelet aggregation, severe thrombocytopenia, and microangiopathic hemolytic anemia. Only sporadic case reports of TMA after cadaveric or living-donor liver transplantation (LDLT) have been described., Methods: The authors report 10 (5% of the total series) TMA patients after LDLT and review the previously reported cases. TMA was diagnosed on the basis of progressive thrombocytopenia of unknown cause and microangiopathic hemolytic anemia, suggested by sharp elevation of serum lactate dehydrogenase levels and the presence of fractionated erythrocytes in blood smear., Results: Of the 10 patients with TMA, 7 presented with viral hepatitis (2 with hepatitis B and 5 with hepatitis C virus infection) as the cause of end-stage liver disease. Clinical diagnosis of TMA was made at a median interval of 18 days (range, 3-356 days) from the time of transplantation. Conversion of calcineurin inhibitors (CNI) was conducted in nine patients. One patient recovered after CNI conversion alone. Plasma exchange was performed in eight patients. Three patients died., Conclusions: Immediate treatment of TMA should be initiated by reduction or conversion of CNI followed by plasma exchange. Hepatitis C virus infection might contribute to the high incidence of TMA in LDLT patients.

Background/aims: Complete outflow is impossible to maintain on both sides in donors undergoing hemi-liver graft harvesting, because the middle hepatic vein (MHV) can be preserved on only one side. The area in which outflow veins are disrupted becomes congested, and does not sufficiently regenerate., Methodology: The subjects of the study were 55 living donors who provided the left liver with caudate lobe, including the MHV. The midpoint between the tributaries of the MHV and the right hepatic vein was determined preoperatively with computed tomography. The midpoint between the tributaries of the MHV and right hepatic vein and the borderline between the right and left liver were used to predict the MHV drainage area volume. Total bilirubin levels, the prothrombin time international normalization ratio, and alanine aminotransferase were measured in donors on postoperative days 1, 3, 5 and 7., Results: The parameters that correlated with the MHV drainage area volume included total bilirubin on days 5 and 7, prothrombin time international normalization ratio on day 3, and alanine aminotransferase on day 7., Conclusions: Middle hepatic vein drainage area volume, calculated using the present method, correlated with early liver function after left liver harvesting with the MHV.

Tacrolimus-based immunosuppression is currently accepted as mainstream therapy in many transplant centers worldwide due to its potent immunosuppressive activity compared to cyclosporine. A tacrolimus-based regimen has been successfully used for our living donor liver transplantation (LDLT) recipients. Adverse effects such as neurotoxicity, nephrotoxicity, and new-onset diabetes mellitus, however, have limited its clinical application. In deceased donor liver transplantation, cyclosporine rescue therapy is valuable for such complications, but few reports have described a strategy for conversion in LDLT. Herein, we present our experience of conversion from tacrolimus to cyclosporine therapy in adult LDLT recipients. Among 203 recipients, 37 patients (18%) required conversion, primarily for neurotoxicity (41%), diabetes mellitus (16%), hematopoietic disorder (16%), and gastrointestinal intolerance (11%). Primary adverse events resolved within 2 months after conversion in 35/37 (94%) of the patients. For LDLT recipients unable to maintain effective immunosuppression with tacrolimus, conversion to cyclosporine is an effective option.

Simultaneous hepatic artery and portal vein thrombosis rarely occurs after liver transplantation. The etiology is unknown. Of 213 patients (72 children and 141 adults) that underwent living donor liver transplantation (LDLT) from January 1996 to March 2003, 4 (2%) developed simultaneous thrombosis at 3 hours to 7 days (median, 4 days) after the operation. Emergent thrombectomy was performed in three patients; the remaining patient was registered in the Japan organ transplant network. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). Portal vein, hepatic artery, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography for 2 weeks after liver transplantation. These parameters were stable until just before the simultaneous thrombosis. These findings indicate that protocol Doppler ultrasonography can diagnose, but not predict, this fatal complication.

Background: Living-donor liver transplantation (LDLT) is important for patients with end-stage viral hepatitis because of the cadaveric organ shortage. Preliminary results, however, indicate that LDLT might be disadvantageous for patients positive for hepatitis C virus (HCV)., Methods: The subjects were 23 patients who underwent LDLT for HCV cirrhosis. All the patients preemptively received antiviral therapy consisting of interferon-alfa2b and ribavirin, which was started approximately 1 month after the operation. The therapy continued for 12 months after the first negative HCV RNA test. The patients were then observed without the therapy for 6 months (group 1). The therapy was continued for at least 12 months even when the HCV RNA test remained positive (group 2). The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy because of early death., Results: Eight patients were removed from the protocol. Nine patients were assigned to group 1 and the other six to group 2. The sustained virologic response ratio was 39% (9 of 23). There was a significant difference between the groups in the histologic activity score 1 year after the therapy. The cumulated 3-year survival of the HCV-positive patients was 85%, which was comparable with that of patients negative for HCV (n=93 [90%])., Conclusions: The present preemptive antiviral protocol after LDLT is safe and might warrant a controlled study for confirming its benefit on graft survival.

There are few reported techniques to minimize the congestion in the donor after left liver graft procuring. If a large tributary of the middle hepatic vein (MHV) draining segment VIII (V8) converges into the root of the MHV in a donor of left liver, this branch should be preserved on the donor side. The volume of congested area when the V8 was ligated was predicted preoperatively by computed tomography (CT) and examined intraoperatively by the clamp test. Postoperative regeneration of the donor liver was evaluated by CT volumetry. This technique was used in 3 cases. The regeneration rate after 3 months of the right paramedian sector was 27, 38, and 8%, and that of the right lateral sector was 31, 63, and 39% in each donor, respectively. No severe complications occurred in the donors. In conclusion, V8 preservation in donors who underwent left liver resection led to satisfactory regeneration both of the right paramedian and lateral sectors and can minimize congestion in remnant liver.

Background: Bile duct-to-duct reconstruction is now used in living-donor liver transplantation (LDLT) for adult patients., Methods: The results of duct-to-duct reconstruction were retrospectively analyzed. The subjects were 81 adult patients who underwent LDLT at the University of Tokyo Hospital with a follow-up period of at least 1 year. The hilar plate of the recipient was dissected to at least the second-order branch of the bile ducts. Duct-to-duct anastomosis was performed with interrupted sutures, and an external stent tube was inserted from the orifice opposite the hilar plate., Results: During the observation period (median, 664 days), biliary complications were observed in 26 cases (32%). The complications included bile juice leakage at the anastomosis or dissection plane of the graft in 12 patients, anastomotic stenosis in 10 patients, and tube trouble in 6 patients. Two patients had bile juice leakage followed by stenosis. Of the 26 patients, 21 required surgical revision., Conclusions: The current technique did not reduce morbidity as expected. Further technical advancement and refinement are needed for better results.

The incidence of hepatic venous complications in partial liver transplantation is more frequent than that in whole liver transplantation. There are no reports of a surgical strategy for hepatic venous outflow block (HVOB) after living-donor liver transplantation. HVOB was diagnosed when the pull-through pressure gradient across the anastomotic site was over 5 mm Hg. Reoperation for venous anastomosis was performed if the angioplasty was unsuccessful. After dissection around the hepatic venous anastomotic site, a patch venoplasty of the anastomosis was performed. When the inferior vena cava was constricted, venoatrial anastomosis was performed. In 6 years, 5 of 223 patients experienced HVOB. Balloon angioplasty was successfully performed in two patients, a patch venoplasty of the anastomosis in two, and venoatrial anastomosis in one. In all patients, the ascites stopped. HVOB must be diagnosed as soon as possible with Doppler ultrasound and venography. Prompt surgical revision can salvage the grafts.

Living donor liver transplantation is important for patients with end-stage viral hepatitis because of the shortage of organs from deceased donors. However, preliminary results indicate that living liver donation might be disadvantageous for hepatitis C virus-positive patients. Twenty-seven patients who underwent living donor liver transplantation for hepatitis C virus cirrhosis preemptively received antiviral therapy using interferon-alpha2b and ribavirin, which was started an average of 32 days after the operation and continued for at least 6 months thereafter. The serum hepatitis C virus RNA became negative in the 8 of 16 patients with more than 1 year follow-up. The cumulative 3-year patient survival was 85%, which was comparable to that of hepatitis C virus negative patients (n = 93; 90%). Preemptive antiviral therapy after transplantation may be necessary for satisfactory results after living donor liver transplantation., (Copyright 2004 Elsevier Inc.)

Short and direct vein anastomosis is generally performed in living donor liver transplantation using a right liver graft. The graft will regenerate, however, and might thus compress the anastomosis. We formulated a strategy for outflow reconstruction in right liver graft. When reconstruction of multiple short hepatic veins was necessary, a cryopreserved inferior vena cava graft was anastomosed with the hepatic veins of the graft in a basin. When there were no major short hepatic veins in the graft, a rectangular-shaped vein graft was used to make a single orifice using the middle and right hepatic veins in the graft. When there were no tributaries of the middle hepatic vein to be reconstructed, a diamond-shaped vein patch was anastomosed on the anterior wall of the right hepatic vein orifice of the graft. These techniques were satisfactorily applied in 40 patients with no torsion or tension at the anastomotic site of the hepatic venous reconstruction or other complications in outflow. The present strategy seemed to be technically feasible for outflow reconstruction in a right liver graft.

After right hepatectomy with the middle hepatic vein trunk for a graft, the venous outflow in segment IV is disturbed. There are limited data, however, regarding the effect of middle hepatic vein deprivation on liver regeneration or functional recovery. Living donors who underwent right hepatectomy with preservation of the middle hepatic vein (Group A, n = 58) and those deprived of the middle hepatic vein (Group B, n = 13) were reviewed. When the donor was under 50 years old and the remnant left liver was estimated to be more than 35% of the whole liver, right liver graft harvesting with the middle hepatic vein trunk was considered. Volume regeneration of segments I-III, segment IV, and overall liver volume was assessed at the third postoperative month using computed tomography. The regeneration rate of segment IV was significantly impaired in Group B donors compared with that in Group A donors (125% vs. 45%, P = 0.008). In contrast, the regeneration rate of segments I -III was significantly higher than that in Group A (208% vs. 263%, P = 0.004). There was no significant difference in the regeneration rate of the whole left liver or functional recovery between groups. Multivariate analysis revealed that the resection type (group) was a significant predictive factor for the regeneration rate of segments I-III and segment IV. When deprived of the middle hepatic vein, liver regeneration of segment IV was impaired but was compensated for by the regeneration of segments I-III. In conclusion, extended right hepatectomy can be safely performed with careful preoperative consideration using these criteria.

Bile duct-to duct reconstruction is now performed in living donor liver transplantation (LDLT) for adult patients. To confirm the feasibility, the results after the reconstruction were retrospectively analyzed. The subjects were 92 adult patients who underwent LDLT at the University of Tokyo Hospital. During the observation period (median 546 days), biliary complications were observed in 28 cases (30%). The complications included bile juice leakage in 11, stenosis at the anastomotic site in 9, and tube trouble in 8. Of these, 20 patients required surgical revision. The results suggest that duct-to-duct reconstruction provides satisfactory results, although long-term observation will be necessary.

The influence of lymphocytotoxic cross-match on survival or acute rejection in living donor liver transplantation (LDLT) has not been well examined. We analyzed 133 consecutive adult LDLT cases and assessed patient survival and acute rejection rates. Patients with a positive T lymphocytotoxic cross-match (n = 12) had a significantly higher chance of rejection within 6 weeks of LDLT (67% versus 28%, P <.001). All of the rejection episodes were successfully treated with bolus methylprednisolone therapy or anti-T cell monoclonal antibody. T lymphocytotoxic cross-match-positive grafts had no influence on patient survival (79% versus 90% at 3 years, P =.91). The results show that a positive cross-match graft should not be considered a contraindication for LDLT.