A hybrid procedure of living donor liver transplantation for a pediatric patient with citrin deficiency.

BACKGROUND: The application of laparoscopic procedures in the liver surgery has been growing. We herein present the first case of a pediatric patient who underwent living donor liver transplantation (LDLT) using a hybrid procedure with hand-assisted laparoscopic mobilization of the liver, subsequent explantation of the diseased liver, and implantation of the graft under direct vision. METHODS: A 12-year-old girl with citrin deficiency was scheduled for LDLT with a left lobe graft. After making an 8-cm upper midline incision, a 5-mm trocar was placed at the umbilicus and the right upper abdomen. Mobilization of the right liver lobe was performed using a hand-assisted laparoscopic surgery (HALS) procedure. After the extension of the midline incision, short hepatic vein dissection, encircling the right hepatic vein and hepatic hilum dissection was performed. Explantation of the liver and subsequent implantation of the liver graft were conducted under direct vision. RESULTS: Since the operation, her normal activities of daily life have been maintained with a normal liver function. Subsequently, her secondary sexual characteristics have recovered without any wound-related complications. CONCLUSIONS: A hybrid LDLT procedure was feasible for a pediatric patient. This procedure's benefits are considered meaningful for pediatric patients as it does not disrupt the rectus muscles or nerves and achieves cosmesis.

Hepatic artery reconstruction preserving the pancreaticoduodenal arcade in pediatric liver transplantation with celiac axis compression syndrome: report of a case.

CACS is rare, although it has been reported to be a potential risk factor for hepatic artery thrombosis following LT. We herein present the case of a 14-yr-old male with stenosis of the origin of the celiac trunk. Preoperative CT and color ultrasonography showed narrowing of the proximal celiac artery. The patient underwent DDLT with standard arterial reconstruction without dividing the gastroduodenal artery. His postoperative course was uneventful, with an excellent hepatic artery flow on Doppler ultrasonography. Applying a meticulous preoperative evaluation and the appropriate surgical technique is crucial in patients with CACS.

Primary liver carcinoma exhibiting dual hepatocellular-biliary epithelial differentiations associated with citrin deficiency: a case report.

We report a 50-year-old male patient with primary liver carcinoma exhibiting dual hepatocellular and biliary epithelial differentiations associated with citrin deficiency (asymptomatic adult-onset type II citrullinemia, CTLN2). Although so far 14 CTLN2 patients with hepatocellular carcinoma have been reported, this report describes a unique case of liver carcinoma showing the features of both hepatocellular and cholangiocellular carcinoma. In addition to the clinical data of the 14 patients reported previously, the findings in our patient suggest that the citrin deficiency might be one of the key disorders causing hepatocellular carcinoma especially at younger ages and can also play an important role in hepatocarcinogenesis of the hepatic progenitor cells, which have the bipotential to differentiate into both hepatocytes and cholangiocytes.

Living donor liver transplantation for type II citrullinemia from a heterozygous donor.

Adult-onset type II citrullinemia (CTLN2) is a rare disorder of the urea cycle resulting in hyperammonemia, with a poor prognosis. Here we report a 48-year-old Japanese man who showed abnormal nocturnal behavior. Laboratory data indicated raised plasma concentrations of ammonia and citrulline, and a definitive diagnosis of CTLN2 was made by DNA analysis. Hyperammonemia was not improved by oral intake of branched-chain amino acids (BCAA), whereas venous infusion of BCAA was effective. Western blotting revealed heterozygotic expression of citrin protein in a liver biopsy specimen from the patient's brother. However, as symptomatic CTLN2 is very unusual in a heterozygotic carrier, we considered the brother suitable as a living-donor liver transplantation (LDLT) donor. The recipient's entire liver was removed, and replaced with the left liver graft. The plasma ammonia level remained low without infusion of BCAA after liver transplantation. From this case we conclude that venous infusion, rather than oral administration, of BCAA is useful for conservative treatment of CTLN2. However, liver transplantation is the only effective therapeutic option for CTLN2, and should be performed before irreversible encephalopathy occurs. Use of a graft from heterozygotic donors is permissible treatment for CTLN2.

[Progresses and perspectives in the study on citrin deficiency].

Citrin deficiency causes autosomal recessive disorders including adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The responsive gene of citrin deficiency, SLC25A13, locates on chromosome 7q21.3 and encodes citrin as a liver-type mitochondrial aspartate/glutamate carrier (AGC). The mutations on SLC25A13 will result in deficiency of citrin and CTLN2 or NICCD. Citrin deficiency was found at first in Japan. However, recently, some of cases were identified in China, Korea, Vietnam, Israel, Czech, United States and England, and racial differences of the SLC25A13 mutations were found, suggesting the patients with citrin deficiency maybe exist worldwide. In this article, authors reviewed the progresses in the study on citrin deficiency up to now and put forward authors' considerations for further research on it.

Allopurinol challenge tests performed before and after living-related donor liver transplantation in citrullinaemia.

We performed allopurinol challenge tests to evaluate the metabolic state of a citrullinaemic patient who received a living-relative donor liver transplant. Before transplantation, large amounts of orotic acid and orotidine were excreted during the challenge test. Following transplantation, excretion of these compounds in response to allopurinol was normalised. The challenge test was a safe and useful method to evaluate the metabolic state of the patient.

Thrombopoietin levels and peripheral platelet counts following living related donor liver transplantation.

BACKGROUND/AIMS: Thrombopoietin is the primary hematopoietic growth factor. Thrombopoietin deficiency may cause thrombocytopenia in advanced liver disease. The aim of our study was to investigate the relevance of thrombopoietin levels to peripheral platelet counts in patients with liver disease who underwent LRDLT (living related donor liver transplantation). METHODOLOGY: We divided the six patients who underwent LRDLT into two groups. Group 1 had thrombocytopenia and group 2 had normal platelet counts. We measured serum thrombopoietin and peripheral platelet counts before and after LRDLT. RESULTS: Pre-LRDLT thrombopoietin and peripheral platelet counts were lower in group 1 than in group 2. Thrombopoietin in group 1 significantly increased on the first day after LRDLT and peripheral platelet counts in group 1 increased following the rise in thrombopoietin (p < 0.05). Moreover, a marked increase in thrombopoietin and peripheral platelet counts was found in splenectomized patients during LRDLT. CONCLUSIONS: These findings suggested inadequate thrombopoietin production in advanced stage liver disease which caused thrombocytopenia. Improvement of thrombopoietin production in graft liver function may contribute to increase of peripheral platelet counts.

A pediatric patient with classical citrullinemia who underwent living-related partial liver transplantation.

Patients with inborn errors of metabolism undergo liver transplantation, but the effect of transplanting the liver of healthy carriers of these conditions has not been fully clarified. A 6-year-old girl with classical citrullinemia, who repeatedly suffered from hyperammonemia, underwent living-related liver transplantation by using a segment of the liver of her mother, who was a heterozygote carrier for classical citrullinemia. Hyperammonemia alleviated in the patient after the transplantation, thereby dramatically improving her quality of life. Although the levels of plasma and urinary citrulline remained high postoperatively, there was no marked difference in the level of plasma citrulline up to 1 month after surgery when compared with that of previously reported orthotopic liver transplantation cases with classical citrullinemia.

Living-related liver transplantation for type II citrullinemia using a graft from heterozygote donor.

BACKGROUND: Type II citrullinemia (CTLN2) characterized by a liver-specific argininosuccinate synthetase deficiency is an adult onset genetical disorder caused by the mutation of SLC25A13 gene, which results in fulminant hyperammonemia often with poor prognosis. METHODS: A 16-year-old Japanese boy presented fulminant hyperammonemia and encephalopathy and recovered after aggressive medical treatment. The patient was diagnosed as CTLN2 by plasma amino acid pattern and detection of the mutated SLC25A13 gene. We performed living-related liver transplantation (LRLT) using a graft from the genetically proven heterozygote father. RESULTS: Serum amino acid concentration was normalized within a day after transplantation without protein restriction and medication. The patient's postoperative course was natural. The patient is back in school 6 months after surgery. CONCLUSIONS: Living-related liver transplantation using a graft from genetically proven heterozygote donors might be a permissible treatment modality for CTLN2. Long-term observation may be necessary to make a definite conclusion possible.

Type II citrullinemia in an elderly patient treated with living related partial liver transplantation.

A 60-year-old woman was admitted to our hospital for repeated consciousness disturbance. Blood examination showed hyperammonemia, and plasma amino acid analysis revealed a marked increase in the citrulline level. To establish a diagnosis, a percutaneous needle biopsy of the liver was performed. The determination of the urea cycle enzyme activities revealed a selective marked decrease in argininosuccinate synthetase activity, indicating the final diagnosis of type II citrullinemia. The mean survival period of this disease after the appearance of symptoms has been reported as 26.4 months, and most conservative treatments are not effective. We performed a living related partial liver transplantation. Over the subsequent 13-month follow-up, the patient's condition has remained fairly good.