岡田 憲樹

In the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible-liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type-incompatible liver transplantation was 128 and eight, respectively (P < 0.05). Eleven courses of apheresis and dialysis were performed post liver transplantation for 10 patients. The median PaO2/FiO2 ratio before and after dialysis for fluid overload was 159 and 339, respectively (P < 0.05). No bleeding or technical complications attributable to apheresis and dialysis occurred. The 1-year survival rate of the patients was 100%. Apheresis and dialysis in pediatric living donor liver transplantation are effective for antibody removal in ABO-incompatible liver transplantation, and fluid management for acute respiratory failure.

症例は9歳男児で、生後3ヵ月に先天性門脈欠損症と診断され、治療抵抗性の抗アンモニア血症、多発肝腫瘍のため8歳時に父親をドナーとするABO血液型適合生体肝移植を施行した。術前cytomegalovirus(CMV)抗体検査ではドナー既感染/レシピエント未感染であった。術後30日目に急性胃腸炎で入院し、いったん改善後に貧血、大量下血を認め、hypovolemic shockの状態となった。更に40℃台の発熱を認め、CMV腸炎による消化管出血の可能性を考え、免疫抑制剤を中止し、γ-globulin、ganciclovirの点滴治療を開始した。下部消化管内視鏡で回盲弁から10cm口側の回腸に出血源と考えられる多発潰瘍を認め、術後41日目のCMV抗原が陽性であり、CMV腸炎を疑った。その後CMV抗原値は減少し、解熱傾向となって免疫抑制剤を再開し、valganciclovir hydrochloride経口投与に変更し退院となった。以後CMV感染症の再燃はなく、術後2年6ヵ月で経過良好である。

当院では2009年1月からグラセプターの使用を開始し、その使用基準は「移植後3年以上経過した5歳以上の症例」としている。今回、具体的な使用方法を紹介し、これまでに使用した28例について報告した。28例の内訳は男性7例、女性21例、年齢5〜19歳(中央値12歳)、移植後年数は4〜18年(中央値9年)であった。グラセプターを導入した理由は「家族や患者の希望」が最も多く13例(46%)、次いで「免疫抑制剤を増量・再開時」11例(39%)、「服薬コンプライアンス不良」4例(14%)であった。グラセプターへの切り替え・導入パターンの内訳は、プログラフ顆粒剤からの切り替え10例(36%)、プログラフカプセル剤からの切り替え10例(36%)、シクロスポリンからの切り替え1例(4%)、カルシニューリン阻害剤(CNI)を中止してからの再開7例(25%)であった。グラセプターの継続使用が可能であった症例の割合は89%であり、CNI中止から再開した症例ではグラセプター導入後に肝機能や病理所見の改善が認められ、服薬コンプライアンス不良に対してグラセプターを導入した症例ではいずれも飲み忘れが減少した。

Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity. Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed. The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001). Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.

Background: Nonanastomotic biliary stricture is generally considered the most troublesome biliary complication after liver transplant. Nonanastomotic biliary stricture owing to immunologic cholangiopathy (such as acute cellular rejection) has not been reported. We describe 2 patients with the co-occurrence of nonanastomotic biliary stricture and acute cellular rejection after pediatric live-donor liver transplant. Case 1: A 13-month-old male infant with liver cirrhosis underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Eighty days after the live-donor liver transplant, fever with liver dysfunction and dilatation of the intrahepatic bile duct occurred. Percutaneous transhepatic biliary drainage and a liver biopsy were performed. The histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. Case 2: A 21-month-old female infant with biliary atresia underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Twenty-six days after the live-donor liver transplant, percutaneous transhepatic biliary drainage for B3 and a liver biopsy were performed, owing to fever, with liver dysfunction, and dilatation of the intrahepatic bile duct. Histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. Conclusions: It is important for patients with nonanastomotic biliary stricture to undergo early liver biopsy because the nonanastomotic biliary stricture may be coincident with, or caused by, acute cellular rejection.

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.

Background and Aims. Congenital extrahepatic portosystemic shunt (CEPS) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. It is still a matter of debate whether conservative or operative strategies should be used to treat symptomatic CEPS. The aim of this study was to evaluate the role of operative intervention in the management of CEPS. Methods. Between June 2004 and August 2010, 6 consecutive patients with symptomatic CEPS were treated in our department. There were 3 male and 3 female patients, with a median age of 3.5 years (range, 1-8). Their demographic, clinical, and laboratory data were analyzed. All patients were scheduled to undergo shunt ligation or liver transplantation Results. Living donor LT was carried out in 4 patients, and shunt ligation in 2. After a median follow-up of 25 months, all the patients are alive currently with marked relief of symptoms. Conclusion. Shunt ligation or LT for symptomatic CEPS is potentially curative. (Surgery 2012;151:404-11.)

There are no objective and concrete guidelines for the management of Ornithine transcarbamylase deficiency (OTCD). Based on previous findings, we hypothesized that patients with OTCD have a low Ornithine transcarbamylase (OTC) activity in the liver, and therefore it would be better to determine the appropriate indications and optimal timing for liver transplantation (LT) based on the OTC activity. However, few data have so far been accumulated on the OTC activity in cases that are indicated for LT. The purpose of the present study was to clarify the OTC activity in cases that were indicated for LT. This study involved thirteen children with OTCD (8 males and 5 females) who underwent LT, and two females with OTCD who did not require LT. The OTC activity of the neonatal onset type ranged from 0% to 7.2%, while that of the late onset type who underwent LT ranged from 4.4% to 18.7%. The OTC activity of the late onset type which did not require LT was 33-38% based on a preoperative needle liver biopsy. Some late onset patients that underwent LT, showed an activity that was as low as that observed in the neonatal onset cases. This is the first report to show the results of measuring the OTC activity for serial OTCD cases indicated for LT. OTC activity might be an indicator to determine the indications for and the timing of LT in the late onset type, however, further investigations are necessary. (C) 2011 Elsevier Inc. All rights reserved.

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.

Background: At the present time, indications of liver transplantation (LT) for jaundice-free biliary atresia (BA) patients include intractable cholangitis, portal hypertension and pulmonary vascular disorders. However, the timing of LT remains unclear. In the current study, we describe the therapeutic strategies for jaundice-free BA patients. Material/Methods: 129 BA patients were undergone LDLT between May, 2001 and April, 2010 in the Department of Transplant Surgery, Jichi Medical University, Japan. Results: The indications of LDLT for jaundice-free BA patients was 30 patients (30/129, 23%), and included portal hypertension (16 patients, 53%). Among the 16 patients with portal hypertension, there were 7 patients (7/16, 23%) in which uncontrollable gastrointestinal bleeding was an indication of LDLT. There were 5 patients (5/7; 71%) in which bleeding sites were not identified, and 3 patients (3/7; 43%) in which supportive treatments against collateral vessels were performed as a previous treatment. Conclusions: Even in jaundice-free BA patients, after supportive treatments for portal hypertension are performed, it is necessary to assess the esophageal and gastrointestinal varices regularly and to also prepare for LT simultaneously because there is a probability of the complication of uncontrollable gastrointestinal bleeding.

P>Bilioenteric anastomotic stricture after liver transplantation is still frequent and early detection and treatment is important. We established the management using double-balloon enteroscopy (DBE) and evaluated the intractability for bilioenteric anastomotic stricture after pediatric living donor liver transplantation (LDLT). We underwent DBE at Jichi Medical University from May 2003 to July 2009 for 25 patients who developed bilioenteric anastomotic stricture after pediatric LDLT. The patients were divided into two types according to the degree of dilatation of the anastomotic sites before and after interventional radiology (IVR) using DBE. Type I is an anastomotic site macroscopically dilated to five times or more, and Type II is an anastomotic site dilated to less than five times. The rate of DBE reaching the bilioenteric anastomotic sites was 68.0% (17/25), and the success rate of IVR was 88.2% (15/17). There were three cases of Type I and 12 cases of Type II. Type II had a significantly longer cold ischemic time and higher recurrence rate than Type I (P = 0.005 and P = 0.006). In conclusion, DBE is a less invasive and safe treatment method that is capable of reaching the bilioenteric anastomotic site after pediatric LDLT and enables IVR to be performed on strictures, and its treatment outcomes are improving. Type II and long cold ischemic time are risk factors for intractable bilioenteric anastomotic stricture.

Background: Although liver transplantation using liver allograft with hemangiomas has been previously reported, little is known about the fate of hemangiomas in the transplanted liver. We herein describe a case of pediatric living donor liver transplantation (LDLT) using living donor liver allograft with a hemangioma which is considered to the first reported case performing in vivo hemangioma resection. Case Report: A 27-year-old female was evaluated as a donor for her 2-year-old son with cholestatic cirrhosis due to biliary atresia. Preoperative ultrasonography and computed tomography revealed a 20-mm hemangioma located at lateral side of segment 3. During LDLT, an in vivo partial hepatic resection of the hemangioma of segment 3 was performed without the Pringle maneuver using intraoperative ultrasonography to keep the main portal triad of segment 3 before the donor liver resection, and the left lateral segment graft without the hemangioma, which underwent an intraoperative pathologic diagnosis, was transplanted into the recipient. The donor's postoperative course was uneventful and the recipient course was not observed subsequent liver necrosis, bleeding or bile leakage from the resection site. Conclusions: Liver allografts with hemangiomas can be accepted as potential liver allografts, and such hemangiomas should undergo be performed in vivo resection during LDLT irrespective of tumor size.

欧米では年間6,000例以上の肝移植が行われ、そのほとんどが脳死肝移植という状況である。生体肝移植が99%を占める日本では、年間120〜140例の小児生体肝移植が行われ、手術手技・免疫抑制療法・感染症治療などの進歩により、その成績は安定してきた。近年、劇症肝不全、代謝性疾患の割合が増えつつあるが、それぞれの疾患に応じた適切なタイミングで肝移植を行うことがさらなる成績向上につながる。小児肝移植後の長期的合併症である血管・胆管の吻合部狭窄やグラフト肝の線維化に対しては、標準的肝機能検査だけでなく、定期的な画像検査や肝生検による早期診断が重要である。生涯にわたりグラフトとレシピエントを守りつづけるためには、移植コーディネーターの充実など、移植システムの整備も必要である。(著者抄録)