Kaoru Taira

Current role of liver transplantation for the treatment of urea cycle disorders: A review of the worldwide English literature and 13 cases at Kyoto University

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden‐onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor‐recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved. (Liver Transpl 2005;11:1332–1342.)

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Forty‐six pediatric patients who underwent living donor liver transplantation (LDLT) using parental liver grafts for inheritable metabolic disorders (IMD) were evaluated to determine the outcomes of the surgery, decisive factors for post‐transplant patient survival and the impact of using donors who were heterozygous for the particular disorder. Disorders included Wilson disease (WD, n = 21), ornithine transcarbamylase deficiency (OTCD, n = 6), tyrosinemia type I (TTI, n = 6), glycogen storage disease (GSD, n = 4), propionic acidemia (PPA, n = 3), methylmalonic acidemia (MMA, n = 2), Crigler‐Najjar syndrome type I (CNSI, n = 2), bile acid synthetic defect (BASD, n = 1) and erythropoietic protoporphyria (EPP, n = 1). The post‐transplant cumulative patient survival rates were 86.8 and 81.2% at 1 and 5 years, respectively. Post‐transplant patient survival and recovery of the growth retardation were significantly better in the liver‐oriented diseases (WD, OTCD, TTI, CNSI and BASD) than in the non‐liver‐oriented diseases (GSD, PPA, MMA and EPP) and pre‐transplant growth retardation disadvantageously affected post‐transplant outcomes. Although 40 of 46 donors were considered heterozygous for each disorder, neither mortality nor morbidity related to the heterozygosis has been observed. LDLT using parental donors can be recommended as an effective treatment for pediatric patients with IMD. In the non‐liver‐oriented diseases, however, satisfactory outcomes were not obtained by hepatic replacement alone.

Single center experience of 39 patients with preoperative portal vein thrombosis among 404 adult living donor liver transplantations.

Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) involves technical difficulty. The aim of this research was to analyze their preoperative diagnosis of PVT, operative procedures, and postoperative courses of patients with preoperative PVT. Thirty‐nine patients of 404 adult patients (9.7%) undergoing LDLT in our hospital from 1996 June to 2004 December had PVT at their transplantation. Twenty‐nine patients had intractable ascites, 21 had gastrointestinal bleeding, and 18 had encephalopathy. The thrombus was located in the portal trunk in 23, in the portal trunk and superior mesenteric vein (SMV) in 7, and developed into the SMV and the splenic vein in 8. The occlusive grade was partial in 29, and complete in 10 patients. The thrombus was removed by a simple technique, and eversion and/or incision technique, or total removal of the portal vein (PV). The PV was reconstructed with the thrombectomized native PV, with an interposed vein graft, or porto‐caval hemitransposition. Advanced PVT had a significant impact on blood loss and hospital mortality. Three out of 10 patients with residual PVT required radiological and/or surgical intervention after transplantation. In conclusion, thorough planning is essential for a successful LDLT outcome for patients with preexisting PVT. Liver Transpl 12:1512–1518, 2006.

Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: The Kyoto experience

Smaller‐size infants undergoing living‐donor liver transplantation (LDLT) are at increased risks of vascular complications because of their smaller vascular structures in addition to vascular pedicles of insufficient length for reconstruction. Out of 585 child patients transplanted between June 1990 and March 2005, 64 (10%) weighing less than 6 kg underwent 65 LDLTs. Median age and weight were 6.9 months (range: 1‐16 months) and 5 kg (range: 2.8‐5.9 kg), respectively. Forty‐five lateral segment, 12 monosegment, and 8 reduced monosegment grafts were adopted, and median graft‐to‐recipient weight ratio was 4.4% (range: 2.3‐9.7). Outflow obstruction occurred in only 1 patient (1.5%). Portal vein complication occurred in 9 (14%) including 5 with portal vein thrombosis. Hepatic artery thrombosis (HAT) occurred in 5 (7.7%). Patient and graft survivals were 73% and 72% at 1 yr, and 69% and 68% at 5 yr after LDLT, respectively. Thirteen of 22 grafts (58%) lost during the follow‐up period occurred within the first 3 months posttransplantation. Overall graft survival in patients with and without portal vein complication was 67% and 65%, respectively (P = 0.54). Overall graft survival in patients with and without HAT was 40% and 67%, respectively. HAT significantly affected graft survival (P = 0.04). In conclusion, our surgical technique for smaller‐size recipients resulted in an acceptable rate of vascular complications. Overcoming early posttransplantation complications will further improve outcomes in infantile LDLT. Liver Transpl 12:1224–1232, 2006.

Living donor liver transplantation with reduced monosegments for neonates and small infants

Background. In pediatric living donor liver transplantation, left lateral segment or monosegmental graft is used to overcome size discrepancies between adult donors and pediatric recipients. For neonates and extremely small infants, however, problems related to large-for-size graft are sometimes encountered even when using such grafts. The reduced monosegmental graft, in which the caudal part of the monosegmental graft is resected, has been introduced to address this problem. Methods. Of 566 children who underwent transplant between June 1990 and September 2004, reduced monosegment living donor liver transplants were used for nine patients (median age, 144 days; median weight, 4.1 kg). This technique was used for infants with estimated graft-to-recipient weight ratio (GRWR) ≥4.0% when using the left lateral segment. Results. Graft and patient survival was 66.7%. GRWR was reduced from 7.45±2.70% to 3.39±0.89% using this modification. Transaminase levels at days 1 and 2 after transplantation were significantly higher in reduced monosegmental transplantation than in left lateral segmental transplantation. Hepatic artery thrombosis and portal vein thrombosis were observed in one case each. Conclusion. Reduced monosegmental living donor liver transplantation represents a feasible option for neonates and extremely small infants with liver failure.

The impact of meticulous management for hepatic artery thrombosis on long‐term outcome after pediatric living donor liver transplantation*

Abstract:  To analyze the risk factors in the development of hepatic artery thrombosis (HAT) and assess the impact of our perioperative management for HAT on the long‐term outcome after pediatric living donor liver transplantation (LDLT), we reviewed 382 patients under 12 yr of age who underwent 403 LDLT from January 1996 to December 2005. One‐ and 10‐yr patient survival rates were 78% and 78% in the patients with HAT (27 patients; 6.7%), and 84% and 76% in the patients without HAT, respectively (p = n.s.). Univariate analysis showed gender (female), body weight (lower), and graft‐to‐recipient weight ratio (higher) were significant risk factors in the patients with HAT (p < 0.05). Patients with Doppler ultrasound signal loss of the hepatic artery (HA) accompanied by an increase of liver enzymes underwent thrombectomy and reanastomosis (S‐group, n = 13), and patients with a weak HA signal underwent anticoagulant therapy (M‐group, n = 13). One patient underwent re‐LDLT. One‐ and five‐yr patient survival rates were 83% and 83% in the S‐group, and 77% and 77% in the M‐group (p = n.s.). The incidence of biliary complications in the S‐group (58%) was significantly higher than that of the M‐group (15%). For a successful long‐term outcome, the early detection of HAT and prompt medical and surgical intervention are crucial to minimize the insult of HAT.

Histological recurrence of autoimmune liver diseases after living-donor liver transplantation

Background:  The effects of living donor liver transplantation (LDLT) on the recurrence of autoimmune liver diseases have not been well documented. Genetic similarities may be beneficial to avoid severe rejection but may facilitate the recurrence of autoimmune diseases. Because familial occurrence of autoimmune liver diseases has been documented, there is a possibility that candidates for living‐related donors may have the same disease as that of the recipients.

Liver transplantation without isoniazid prophylaxis for recipients with a history of tuberculosis

Abstract:  Tuberculosis remains one of the most serious infections after organ transplantation. Isoniazid prophylaxis for liver transplant recipients with a history of tuberculosis is generally recommended. However, its benefit is controversial because of potential hepatotoxicity of isoniazid. It is crucial to determine appropriate post‐transplant managements for the recipients with a history of tuberculosis. The purpose of this study was to investigate the necessity of isoniazid prophylaxis for liver transplant recipients who had a history of tuberculosis. The medical records of 1116 liver transplant recipients were studied, of whom seven had a history of tuberculosis (0.63%). One who underwent living‐donor liver transplantation for fulminant hepatic failure was excluded from evaluation because of early death, caused by bacterial sepsis two months after transplantation, although reactivation of tuberculosis was not observed. The median observation period after transplantation was 25.5 months (range 12–82). Reactivation of tuberculosis did not occur in any of these six patients. In conclusion, we could not find rationale for isoniazid prophylaxis in liver transplant recipients with past diagnosis of tuberculosis, when the disease is considered to be inactive. Tuberculosis should be considered as cause of post‐transplant infections, and careful post‐transplant observations are essential for an early diagnosis.

Development of pulmonary hypertension in 5 patients after pediatric living‐donor liver transplantation: De novo or secondary?

The development of portopulmonary hypertension (PH) in a patient with end‐stage liver disease is related to high cardiac output and hyperdynamic circulation. However, PH following liver transplantation is not fully understood. Of 617 pediatric patients receiving transplants between June 1990 and March 2004, 5 (median age 12 yr, median weight 24.5 kg) were revealed to have portopulmonary hypertension (PH) after living‐donor liver transplantation (LDLT), as confirmed by echocardiography and/or right heart catheterization. All children underwent LDLT for post‐Kasai biliary atresia. In 2 patients with refractory biliary complications, PH developed following portal thrombosis; 2 with stable graft function, who had had intrapulmonary shunting (IPS) before LDLT, were found to have PH in spite of overcoming liver dysfunction due to hepatitis. PH developed shortly after distal splenorenal shunting in 1 patient, who suffered liver cirrhosis due to an intractable outflow blockage. The onset of PH ranged from 2.8 to 11 yr after LDLT, and mean pulmonary artery pressure (mPAP) estimated by echocardiography at the time of presentation ranged from 43 to 120 mmHg. Three of the 5 patients are alive under prostaglandin I2 (PGI2) treatment. Of these, 1 is prepared for retransplantation for an intractable complications of liver allograft, while the other 2 with satisfactory grafts are being considered for lung transplantation. Even after LDLT, PH can develop with portal hypertension. Periodic echocardiography is essential for early detection and treatment of PH especially in the recipients with portal hypertension not only preoperatively but also postoperatively. Liver Transpl 12:870–875, 2006.

Cytomegalovirus infection with perineal pain after living donor liver transplantation: report of four cases

Abstract: We report on 4 adult cases of presumptive cytomegalovirus (CMV) disease with perineal pain after living donor liver transplantation. Patients presented with severe perineal pain without any other symptoms related to CMV infection, except pyrexia. All patients had an episode of acute cellular rejection (ACR) before the onset of perineal pain, and 1 patient needed OKT3 therapy. The severe perineal pain was not well controlled with medication, and 1 patient needed epidural anesthesia. In the first 3 patients, pp65 CMV antigenemia (pp65CMV‐Ag) test results were positive and intravenous administration of ganciclovir (GCV) therapy was initiated. In the last patient, GCV therapy was preemptively administered before a positive pp65CMV‐Ag test result was confirmed. After administration of GCV, the pain gradually disappeared and all patients had negative pp65CMV‐Ag test results. In conclusion, unusual perineal pain can be a symptom related to CMV infection. CMV infection needs to be kept in mind when a liver transplant recipient has severe perineal pain, especially after receiving treatment for ACR.