Shinya Otomo

The role of operative intervention in management of congenital extrahepatic portosystemic shunt

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 (LT). 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.

Impact of enzyme activity assay on indication in liver transplantation for ornithine transcarbamylase deficiency.

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.

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.

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.

Non‐alcoholic steatohepatitis caused by malnutrition after pediatric liver transplantation

The IgG2 subclass antibody mainly contains antibodies to the polysaccharides of the bacteria, whereas IgG1 subclass includes antibodies to the protein antigen of the virus. The subject has been susceptible to bacterial infections. His immune response to VZV was thought to be normal, because his cellular immunity using flow-cytometry and his intradermal response to varicella antigen were normal; furthermore, his chickenpox infection was usual based on his medical history. In addition, this patient has led a normal life and we have not found oral candidiasis or Pneumocystis jirovecii. However, he has no secretory IgA antibodies on the mucous membranes, so he is thought to be extremely sensitive to VZV exposure. In the 4 years after natural varicella infection, the subject’s IgG antibody titers slowly decreased to the basal ones, and then the antibody titers increased twice more than the basal ones over the next 6 years. These incidents are not thought to be accidentally high, because the titer in the next sample was also higher than the basal ones. The possibility of this increase of antibody titers indicates the booster effect due to exposure to outer VZV or inner one, which is subclinical reactivation. We believe that these incidents should be boosted by exposure to outer VZV. Although we have not measured the specific cellular immunity against VZV, we think that it had been maintained because he had been followed up from 7 to 17 years old after he had contracted chickenpox at 6 years old and his IgM antibody against VZV has been constantly negative. Chickenpox in infancy is a risk factor for zoster and subclinical reactivation of VZV. The increased IgG titer decreased to the basal titers within 8 months, which is a shorter period than we expected. The immune response between individuals may be different; furthermore, the results may also differ with each kit used to measure antibodies. However, we will be able to deduct the general tendency for the alterations of the antibodies in this case. Although previous reports were searched thoroughly, none was found regarding individual changes of VZV antibodies over a period as long as 10 years. This report is a secondary publication of a case report written in Japanese.

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.

Antenatal immunoglobulin for prevention of neonatal hemochromatosis

Neonatal hemochromatosis (NH) is a rare disease with a poor prognosis, particularly prior to 2008. Antenatal maternal high‐dose immunoglobulin (Ig) is effective in preventing NH recurrence, but the adverse effects of this treatment have not been documented as yet. Here, we report on a patient who underwent high‐dose Ig treatment to prevent NH recurrence. The patient was a 31‐year‐old pregnant Japanese woman. Her first child died of NH after receiving living donor liver transplantation. The patient received high‐dose Ig treatment to prevent recurrence of NH from gestational weeks 16 to 35. During the treatment, platelet count gradually decreased, and cesarean section was required at 35 gestational weeks. The child did not develop liver failure. High‐dose Ig prevented the recurrence of NH. Caution should be exercised due to possible adverse effects of this treatment.

Interventional radiology treatment for vascular and biliary complications following pediatric living donor liver transplantation - a retrospective study

There are few long‐term outcome reports for interventional radiology (IVR) treatments for vascular and biliary complications following pediatric living donor liver transplantation (LDLT). Herein, we presented our institutions experience and investigated the efficacy and issues of long‐term outcome with IVR treatments. Between May 2001 and September 2016, 279 pediatric LDLTs were performed. The median age at LDLT was 1.4 years old, and the median observation period was 8.2 years. All the biliary reconstructions at LDLT were hepaticojejunostomy. The IVR treatments were selected as endovascular, radiological, or endoscopic interventions. Post‐transplant hepatic vein, portal vein, hepatic artery, and biliary complications were present in 7.9%, 14.0%, 5.4%, and 18.3%, respectively. IVR treatment was the first treatment option in 81.8%, 94.9%, 46.7%, and 94.1%, respectively. The recurrence and cure rates following IVR treatment were 42.1%, 21.1%, 44.4%, and 34.0% and 84.2%, 97.4%, 100%, and 88.0%, respectively. The graft survival rates in patients with and without post‐transplant vascular and biliary complications were 94.4% and 90.6%, respectively (P = 0.522). The IVR treatments for vascular and biliary complications following pediatric LDLT are the first choice option. Although the recurrence following IVR treatment is a major problem and it is necessary to carefully perform long‐term follow‐up, IVR treatments have good treatment outcomes.

Increased tacrolimus blood concentration by Beni‐Madonna – a new hybrid citrus cultivar categorized as ‘Tangor’, in a liver transplant patient: likely furanocoumarin‐mediated inhibition of CYP3A4 or P‐glycoprotein

A drug interaction leading to greater exposure to tacrolimus.

Rescue case of low birth weight infant with acute hepatic failure

We report a case involving a rescued low birth weight infant (LBWI) with acute liver failure. Case: The patient was 1594 g and 323/7 gestational wk at birth. At the age of 11 d, she developed acute liver failure due to gestational alloimmune liver disease. Exchange transfusion and high-dose gamma globulin therapy were initiated, and body weight increased with enteral nutrition. Exchange transfusion was performed a total of 33 times prior to living donor liver transplantation (LDLT). Her liver dysfunction could not be treated by medications alone. At 55 d old and a body weight of 2946 g, she underwent LDLT using an S2 monosegment graft from her mother. Three years have passed with no reports of intellectual disability or liver dysfunction. LBWIs with acute liver failure may be rescued by LDLT after body weight has increased to over 2500 g.