Impact of Smoking Cessation in Donor Candidates for Living Donor Liver Transplantation.

BACKGROUND: The relationship between smoking cessation and weight gain is well recognized. Examining the link between smoking cessation and weight gain in donor candidates for living donor liver transplantation (LDLT) is an important topic because of the influence of weight gain on the liver. This study assessed body weight (BW) changes after smoking cessation in donor candidates for LDLT. METHODS: The 27 donor candidates were retrospectively analyzed. The smoking status was determined based on questionnaires administered at the initial presentation, and the candidates were divided into 2 groups: recent quitters and nonsmokers. The changes in BW were compared between the groups. RESULTS: The recent quitters group included 10 (37.0%) candidates, and the nonsmokers group included 17 (63.0%). In the nonsmokers group, 1 candidate had gained weight since the initial presentation. In contrast, in the recent quitters group, 70.0% of candidates had gained weight since the initial presentation (P < .01). The change in BW from the initial presentation was greater in recent quitters than in nonsmokers (+1.6 kg [+2.4%] vs -0.5 kg [-0.9%]; P < .01). Two candidates in the recent quitters group gained ≥ 5 kg [8%] of weight. One of these 2 candidates was judged to be in a donor-inadequate status because of the appearance of fatty liver. CONCLUSIONS: Weight gain due to smoking cessation was observed in donor candidates for LDLT. The amount of weight gain after smoking cessation is highly individualized, so everyone concerned with LDLT must be alert to its potential development.

Long-term Changes in Spleen Volume After Living Donor Liver Transplantation in Pediatric Recipients.

BACKGROUND: Living donor liver transplantation (LDLT) is a definitive procedure for splenomegaly caused by liver cirrhosis and portal hypertension, but splenomegaly persists in some patients. The aim of this study was to clarify the long-term changes in the spleen volume after LDLT. METHODS: The 13 pediatric patients who survived for >8 years after LDLT were retrospectively analyzed. We calculated the spleen volume/standard spleen volume (SV/SSV) ratio by automated computed tomography (CT) volumetry. We assessed the spleen volumes before LDLT, at roughly postoperative week (POW) 4, at postoperative year (POY) 1, at POY 5, and at POY 10. RESULTS: With regard to SV as evaluated by CT volumetry, there were no consistent trends, with median values as follows: before LDLT, 282.5 (71-641) cm3; POW 4, 252 (109-798) cm3; POY 1, 222.5 (97-948) cm3; POY 5, 263.5 (123-564) cm3; and POY 10, 377 (201-1080) cm3. In contrast, the SV/SSV ratio decreased chronologically as follows: before LDLT, 5.0 (0.7-6.0); POW 4, 3.7 (2.3-4.3); POY 1, 2.2 (1.7-6.3); POY 5, 1.7 (1.1-5.4); and POY 10, 1.4 (1.1-6.9). In the remote phase after LDLT, many cases showed a trend toward an improved SV/SSV ratio, but splenomegaly was prolonged without improvement in 3 cases (23.1%) with portal vein complications and advanced fibrosis. Furthermore, all 3 cases showed a decreased platelet count due to hypersplenism. CONCLUSION: Splenomegaly requires a long time to demonstrate an improvement. In cases without an improvement of splenomegaly, we should suspect abnormalities in the graft liver and portal hemodynamics.

Living-Donor Liver Transplantation With the Use of a Left-Lobe Graft From a Donor With Anomalous Biliary Anatomy in Which B4 Joins the Right Anterior Sectional Duct: A Case Report.

When there is an anatomic anomaly in the biliary tract of the donor for living-donor liver transplantation, the risk of postoperative biliary tract complications increases in both the donor and the recipient. We studied a case of living-donor liver transplantation with a left hepatic lobe graft that had anatomic anomalies, in which the medial segmental branch (B4) joined the anterior segmental branch and the posterior segmental branch formed a common trunk with the lateral segmental branch. A 40-year-old man visited our institution as a candidate organ donor for his mother, who had end-stage liver failure. An anomaly of B4 connecting the anterior segmental branch was suspected on magnetic resonance cholangiopancreatography. On intraoperative cholangiography, confluence of B4 with the anterior segmental branch and connection of the posterior and lateral segmental branches forming a common trunk were confirmed. Accordingly, individual anastomoses of the lateral segmental branch and B4 with the recipient jejunum were planned, and a left-lobe graft was excised. The postoperative recovery was smooth, and the donor was discharged with no complications. Even when an anatomic anomaly is present in the donor bile duct, in urgent cases, accurate evaluation through the use of various modalities may enable living-donor liver transplantation with the use of a graft with an anatomic anomaly.

Iron overload after pediatric liver transplantation: a case report.

Iron is an essential nutrient for living cells; however, an excessive accumulation of iron leads to organ damage and directly affects systemic immunity. Iron overload is clinically classified as hereditary or secondary. Most of secondary iron overload is caused by frequent blood transfusions because there is no active mechanism to excrete iron from the body. As recommended in various guidelines, chelation therapy is effective for reducing iron burden and improving organ function. There have been few reports on iron overload through blood transfusion during the perioperative period of liver transplantation. This report presents a case of iron overload due to repeated transfusions after pediatric liver transplantation managed by chelation therapy. The patient, an 11-month-old female with biliary atresia, underwent living donor liver transplantation. She revealed refractory anemia and required frequent blood transfusion. Both serum ferritin and transferrin saturation tended to increase after repeated transfusions, leading to secondary iron overload. Iron chelation therapy was started to prevent progression to organ failure and infection due to iron overload, and yielded a favorable outcome. It is crucial to consider the possibility of secondary iron overload and to achieve early detection and treatment to avoid progression to irreversible organ damage.

Successful treatment of severe anastomotic stricture of a choledochojejunostomy after living donor liver transplantation with transhepatic cholangioscopy-guided balloon dilatation.

Anastomotic stricture of the choledochojejunostomy is a common complication after living donor liver transplantation. Most anastomotic strictures can be treated by percutaneous transhepatic cholangiodrainage and/or double balloon endoscopy. However, in severe cases and/or in small infants, neither of these is possible. Our new technique, cholangiography accompanied by cholangioscopy, enabled successful guidewire placement and balloon dilatation in cases with severe anastomotic stricture.

A comparison of open surgery and endovascular intervention for hepatic artery complications after pediatric liver transplantation.

There are currently 2 major therapeutic options for the treatment of hepatic artery complications: endovascular intervention and open surgery. We herein report a retrospective analysis of 14 pediatric patients with hepatic artery complications after pediatric living donor liver transplantation (LDLT) at our institution. We divided them into an open surgery group and an endovascular intervention group based on their primary treatment, and compared the results and outcomes. We then evaluated which procedure is more effective and less invasive. In the open surgery group, recurrent stenosis or spasm of the hepatic artery occurred in 3 of the 8 patients (37.5%). In the endovascular intervention group, 5 of the 6 patients were technically successfully treated by only endovascular treatment. Of the 5 successfully treated patients, 3 developed recurrent stenosis (60%). There were significant differences in the mean length of the operation for the first treatment of hepatic artery complications (open surgery, 428 minutes vs endovascular intervention, 160 minutes; P = .01) and in the mean value of the posttreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (open surgery > endovascular intervention; P = .04/.05). Although endovascular intervention needs to be examined in further studies to reduce the rate of relapse, it is a less invasive method for the patient and graft than open surgery.

Prediction of acute cellular rejection by peripheral blood eosinophilia in pediatric living donor liver transplantation.

BACKGROUND: Acute cellular rejection (ACR) is a common cause of morbidity following liver transplantation. Several reports have evaluated the predictive value of peripheral blood eosinophilia as a simple noninvasive diagnostic marker for ACR. This study examined whether the relative eosinophil counts (REC) predicted ACR in pediatric living donor liver transplantation (LDLT). METHODS: One hundred three patients underwent LDLT between May 2001 and December 2007. ACR were diagnosed based on the pathological findings. RESULTS: The incidence of ACR was 46.6% (48/103); ACR was diagnosed an average of 13.5 days after LDLT. The average REC at 4 and 2 days before the onset ACR (n = 39) within 30 postoperative day (POD) was 4.3% and 7.3%, respectively, and 9.0% at the onset. Patients with ACR showed significantly higher levels of REC compared with those free of ACR (P = .039). REC thresholds of 10% at POD 7 displayed a sensitivity and specificity of ACR detection of 80% and 75%, respectively. Moreover, the accumulated morbidity ratio of ACR within 30 POD was significantly higher with REC >10% at POD 7 (P = .007). CONCLUSION: ACR within POD 30 should be considered when REC is >10% at POD 7 after LDLT.

Living donor liver transplantation from an asymptomatic mother who was a carrier for ornithine transcarbamylase deficiency.

Liver transplantation (LT) has been adopted as a radical treatment for ornithine transcarbamylase deficiency (OTCD), yielding favorable outcomes. Despite the fact that it is an inheritable disease, a blood relative who is heterozygous for the disorder must sometimes be used as a liver donor for living donor LT. There is ongoing discussion regarding the use of heterozygous donors, however, to our knowledge, no cases where donation was determined based on the Ornithine transcarbamylase (OTC) activity before LT have been reported. Between May 2001 and April 2011, 17 patients were indicated for living donor LT because of OTCD at our facility. There were three cases with heterozygous donor candidate (17.6%). All heterozygous candidates underwent a liver biopsy to measure their OTC activity before LT and made efforts to secure the safety of the both donor and recipient. Two of 3 candidates had headaches sometimes, and their activity was less than 40%, and thus they were not employed as the donor. One candidate with 104.4% activity was employed, yielding favorable outcomes. Our current experience supported the effectiveness of our donation criteria, however it is necessary to collect sufficient data on a large number of patients to confirm the safety of the procedure.

Varicella zoster virus disease after pediatric living donor liver transplantation: is it serious?

OBJECTIVES: The aim of this study was to evaluate patients who developed varicella zoster virus (VZV) disease after pediatric living donor liver transplantation (PLDLT). METHODS: Two hundred fifty-five patients who underwent PLDLT between 1995 and 2010 were included in this study. Pretransplantation vaccination of VZV was performed for all recipients except emergency PLDLTs. Posttransplantation VZV vaccination was administered to the patients with a low VZV antibody titer 2 years or more after transplantation. The clinical course and outcomes of VZV disease in cases were reviewed with the transplant database and hospital medical records. RESULTS: Sixty-three patients developed VZV disease (chicken pox in 61, herpes zoster in 2) at a median onset of 36 months after PLDLT and at a median age of 4 years old, with a cumulative incidence of 25%. All chicken pox occurred in VZV antibody-negative patients. The onset of herpes zoster in the two patients occurred within 3 months after PLDLT; in addition, these patients were VZV antibody-positive patients. The clinical presentations of most patients were not serious and there were no disseminated infections. Although only 3 patients (5%) were hospitalized, the other 60 patients (95%) all showed a good response to oral antiviral therapy. CONCLUSIONS: Although VZV disease is an infectious disease with a high morbidity rate after PLDLT, it can normally be successfully managed on an outpatient basis at home. Pre- and posttransplantation vaccinations are effective for delaying the onset of chicken pox after PLDLT and to prevent it from developing into a serious illness.

Veno-occlusive disease/sinusoidal obstruction syndrome associated with potential antibody-mediated rejection after pediatric living donor liver transplantation: a case report.

A 9-month-old girl with biliary atresia underwent successful living donor liver transplantation from her 42-year-old ABO blood-type incompatible mother. The postoperative course was uneventful until postoperative day (POD) 13 when the recipient displayed an increased volume of drained ascites and decreased her platelet count showing low-velocity portal venous inflow without hepatic venous outflow obstruction. We suspected potential veno-occlusive disease/sinusoidal obstruction syndrome (vod/sos) due to an acute cellular rejection (ACR) episode and performed a liver biopsy (LB). We diagnosed severe episode (Rejection Activity Index Score; P3V3B1 = 7) and started steroid pulse therapy. We performed a second LB on POD 27 because the patient showed weight gain and tender hepatomegaly, diagnosing moderate ACR (P1V3B1 = 5). We started a second course of steroid pulse therapy, but the patient's clinical findings did not improve. On POD 43, her third LB finding showed P1V1B1 with improved processes from ACR, but still displaying severe congestion and fibrotic obliteration of small hepatic veins. We suspected that her immunologic responses were associated with antibody-mediated rejection (AMR) because her anti-HLA class I and class II antibodies were positive by flow panel-reactive antibody method and donor-specific antigen class II and C4d staining were also positive. We added mycophenolate mofetil and administered high-dose intravenous immunoglobulin to control the AMR, and anticoagulant therapy for the VOD/SOS. Her clinical findings and graft venous abnormalities finally improved; she was eventually discharged without sequelae on POD 72.

Living donor liver transplantation in children with cholestatic liver disease: a single-center experience.

OBJECTIVES: Cholestatic liver disease (CLD) is the main indication for liver transplantation in children. This retrospective study evaluated the outcomes of living donor liver transplantation (LDLT) in children with CLD. METHODS: One hundred fifty-nine children with CLD who underwent 164 LDLT between May 2001 and May 2011 were evaluated. Their original diseases were biliary atresia (n=145, 91%), Alagille syndrome (n=8, 5%), primary sclerosing cholangitis (n=2), and the others (n=4). The mean age and body weight of the recipients at LDLT was 42±53 months and 14.0±11.0 kg, respectively. RESULTS: Parents were living donors in 98%. The left lateral segment was the most common type of graft (77%). There were no reoperations and no mortality in any living donor. Recipients' postoperative surgical complications consisted mainly of hepatic arterial problems (7%), hepatic vein stenosis (5%), portal vein stenosis (13%), biliary stricture (18%), intestinal perforation (3%). The overall rejection rate was 31%. Cytomegalovirus infection and Epstein-Barr virus disease were observed in 26% and 5%, respectively. Retransplantation was performed five times in four patients; the main cause was hepatic vein stenosis (n=3). Four patients died; the main cause was gastrointestinal perforation (n=2). The body height of Alagille syndrome patients less than 2 years old significantly improved compared with older patients after LDLT. The 1-, 5-, and 10-year patient survival rates were 98%, 97%, and 97%, respectively. CONCLUSIONS: LDLT for CLD is an effective treatment with excellent long-term outcomes.

Interventional radiology for hepatic artery complications soon after living donor liver transplantation in a neonate.

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.

Hepatic artery reconstruction with the jejunal artery of the Roux-en-Y limb in pediatric living donor liver re-transplantation.

When re-anastomosis and re-transplantation becomes necessary after LDLT, arterial reconstruction can be extremely difficult because of severe inflammation and lack of an adequate artery for reconstruction. Frequently, the recipient's HA is not in good condition, necessitating an alternative to the HA. In such cases, the recipient's splenic artery, right gastroepiploic artery or another vessel can be safely used for arterial reconstruction. There have, however, been few reports on using the jejunal artery. Herein, we report our experience with arterial reconstruction using the jejunal artery of the Roux-en-Y limb as an alternative to the HA. A three-yr-old girl who had developed graft failure due to early HA thrombosis after LDLT required re-transplantation. At re-transplantation, an adequate artery for reconstruction was lacking. We reconstructed the artery by using the jejunal artery of the Roux-en-Y limb, as we judged it to be the most appropriate alternative. After surgery, stent was deployed because hepatic blood flow had reduced due to kinking of the anastomosed site, and a favorable outcome was obtained. In conclusion, when an alternative to the HA is required, using the jejunal artery is a feasible alternative.

Hepatic arterial buffer response after pediatric living donor liver transplantation: report of a case.

BACKGROUND: Excessive portal pressure at an early stage after living-donor liver transplantation (LDLT) can damage sinusoidal endothelial cells and hepatocytes through shear stress leading to graft failure, or hepatic arterial complications due to low hepatic artery flow from a hepatic arterial buffer response. We encountered a case in which excessive portal vein flow was observed from an early stage after pediatric LDLT. The hepatic artery flow decreased due to a hepatic arterial buffer response. CASE REPORT: A 6-month-old boy with biliary atresia showed excessive portal vein flow early after LDLT with a decreasing hepatic artery flow without anastomotic stenosis from postoperative day 3. The PV flow gradually exhibited a decrease at approximately postoperative day 8 and, similtaneously, hepatic artery flow exhibited improvement. CONCLUSION: Because excessive portal pressure after LDLT is reversible, it has been suggested that it may be possible to prevent the progress of hepatic arterial complications if temporary portal pressure modulation can be performed for cases among the high-risk group for hepatic arterial complications.

Pediatric liver retransplantation from living donors can be considered as a therapeutic option for patients with irreversible living donor graft failure.

Liver retransplantation (re-LT) is required in patients with irreversible graft failure, but it is a significant issue that remains medically, ethically, and economically controversial, especially in living donor liver transplantation (LDLT). The aim of this study was to evaluate the outcome, morbidity, mortality, safety and prognostic factors to improve the outcome of pediatric living donor liver retransplantation (re-LDLT). Six of 172 children that underwent LDLT between January 2001 and March 2010 received a re-LDLT and one received a second re-LDLT. The overall re-LDLT rate was 3.5%. All candidates had re-LDLT after the initial LDLT. The overall actuarial survival of these patients was 83.3% and 83.3% at one and five yr, respectively. These rates are significantly worse than the rates of pediatric first LDLT. Vascular complications occurred in four patients and were successfully treated by interventional radiologic therapy. There were no post-operative biliary complications. One case expired because of hemophagocytic syndrome after re-LDLT. Although pediatric re-LDLT is medically, ethically, and economically controversial, it is a feasible option and should be offered to children with irreversible graft failure. Further investigations, including multicenter studies, are therefore essential to identify any prognostic factors that may improve the present poor outcome after re-LDLT.

Living donor liver transplantation for ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency, the most common urea cycle disorder, causes hyperammonemic encephalopathy and has a poor prognosis. Recently, LT was introduced as a radical OTCD treatment, yielding favorable outcomes. We retrospectively analyzed LT results for OTCD at our facility. Twelve children with OTCD (six boys and six girls) accounted for 7.1% of the 170 children who underwent LDLT at our department between May 2001 and April 2010. Ages at LT ranged from nine months to 11 yr seven months. Post-operative follow-up period was 3-97 months. The post-operative survival rate was 91.7%. One patient died. Two patients who had neurological impairment preoperatively showed no alleviation after LT. All patients other than those who died or failed to show recovery from impairment achieved satisfactory quality-of-life improvement after LT. The outcomes of LDLT as a radical OTCD treatment have been satisfactory. However, neurological impairment associated with hyperammonemia is unlikely to subside even after LT. It is desirable henceforth that more objective and concrete guidelines for OTCD management be established to facilitate LDLT with optimal timing while avoiding the risk of hyperammonemic episodes.

Living-donor liver transplantation in 126 patients with biliary atresia: single-center experience.

OBJECTIVES: To describe our experience with 126 consecutive living-donor liver transplantation (LDLT) procedures performed because of biliary atresia and to evaluate the optimal timing of the operation. PATIENTS AND METHODS: Between May 2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8 (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The left lateral segment was the most commonly used graft (75%). Patients were divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40); group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical records were reviewed retrospectively. Follow up was 4.5 (2.7) years. RESULTS: All group 3 donors underwent left lobectomy, and all group 1 donors underwent left lateral segmentectomy. No donors required a second operation or died. Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver Disease score in group 1 was highest, operative blood loss in group 2 was lowest (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic artery complications occurred more frequently in group 1 (17.9%), and biliary stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%, and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were 92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was the primary cause of death. CONCLUSIONS: Living-donor liver transplantation is an effective treatment of biliary atresia, with good long-term outcome. It seems that the most suitable time to perform LDLT to treat biliary atresia is when the patient weighs 8 to 20 kg.

Management of intra-abdominal drain after living donor liver transplantation.

BACKGROUND: There have been few reports on the management of intra-abdominal drains after living donor liver transplantation (LDLT). We retrospectively investigated changes in ascitic data related to management of an intra-abdominal drain. PATIENTS AND METHODS: Between March 2008 and June 2009, we performed 28 LDLT. On the first and the fifth postoperative day (POD) after LDLT, we examined the number of ascites cells and cell fractions as well as performed biochemical examination and cultures. RESULTS: The day of removal of the drain for massive ascites (10 mL/kg/d or more) was 14.2 ± 5.4 POD; for less than 10 mL/kg/d it was 8.7 ± 1.9 POD (P < .001). Nine patients were ascites culture positive; long-term placement of the drain caused an infection in two patients. CONCLUSIONS: When the amount of ascitic fluid on the fifth POD after LDLT was small, it was important to assess the properties of the ascitic fluid because of the possibility of a drain infection or of poor drainage. If the ascitic neutrophil count is less than 250/mm(3) or the examined ascites is normal, intra-abdominal drains should be removed.

Living donor liver transplantation for neonates using segment 2 monosubsegment graft.

The prognosis of liver transplantation for neonates with fulminant hepatic failure (FHF) continues to be extremely poor, especially in patients whose body weight is less than 3 kg. To address this problem, we have developed a safe living donor liver transplantation (LDLT) modality for neonates. We performed LDLTs with segment 2 monosubsegment (S2) grafts for three neonatal FHF. The recipient age and body weight at LDLT were 13-27 days, 2.59-2.84 kg, respectively. S2 or reduced S2 grafts (93-98 g) obtained from their fathers were implanted using temporary portacaval shunt. The recipient portal vein was reconstructed at a more distal site, such as the umbilical portion, to have the graft liver move freely during hepatic artery (HA) reconstruction. The recipient operation time and bleeding were 11 h 58 min-15 h 27 min and 200-395 mL, respectively. The graft-to-recipient weight ratio was 3.3-3.8% and primary abdominal wall closure was possible in all cases. Although hepatic artery thrombosis occurred in one case, all cases survived with normal growth. Emergency LDLT with S2 grafts weighing less than 100 g can save neonates with FHF whose body weight is less than 3 kg. This LDLT modality using S2 grafts could become a new option for neonates and very small infants requiring LT.

Living donor liver transplantation for congenital absence of the portal vein.

The congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. Liver transplantation (OLT) may be indicated for patients with symptomatic CAPV refractory to medical treatment, especially due to hyperammonemia, portosystemic encephalopathy, hepatopulmonary syndrome, or hepatic tumors. Because portal hypertension and collateral circulation do not occur with CAPV, significant splanchnic congestion may occur when the portocaval shunt is totally clamped during portal vein (PV) reconstruction in OLT. This phenomenon results in severe bowel edema and hemodynamic instability, which negatively impact the patient's condition and postoperative recovery. We have successfully reconstructed the PV in living donor liver transplantation (LDLT) using a venous interposition graft, which was anastomosed end-to-side to the portocaval shunt by a partial side-clamp, using a patent round ligament of the liver, which was anastomosed end-to-end to the graft PV with preservation of both the portal and caval blood flows. Owing to the differences in anatomy among patients, at LDLT for CAPV liver transplant surgeons should seek to preserve both portal and caval blood flows.