Po-Ping Liu

Outcome of living donor liver transplantation for glycogen storage disease.

GLYCOGEN storage diseases (GSD) are inherited disorders in which the amount and/or structure of glycogen in body tissues are abnormal. GSD I (von Gierke disease) is caused by a deficiency of glucose 6-phosphatase activity in the liver, kidney, and intestinal mucosa with glycogen overloading in these organs. The clinical manifestations are seizures, systemic acidosis, hyperlipidemia, hyperuricemia, and growth retardation. Without effective treatment, long-term complications occur, including gout, osteoporosis, short stature, and hepatic adenomas. GSD III (Cori disease) is caused by a deficiency of glycogen debranching enzyme activity and characterized with limit dextrin-like glycogen accumulated in both liver and muscle in most patients. Hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation are the main manifestations in children; while liver cirrhosis and /or hepatocellular carcinoma may occur later. Great progress in the management of GSD I and III has been made recently. For patients affected with GSD I, nocturnal nasogastric feeding of glucose or orally administered uncooked cornstarch is effective. With early diagnosis and initiation of treatment, normal growth and development may be expected. Some patients are free of long-term complications. Treatment of GSD III consists of highprotein diet, and frequent high carbohydrate meals for patients with hypoglycemia. Nocturnal gastric feeding or cornstarch supplements comprise effective therapy. However, some patients with GSD do not respond to diet therapy and may need frequent intravenous glucose infusions and even parenteral nutrition to maintain metabolic homeostasis. Liver transplantation (LT) is considered to correct the metabolic defects and the deleterious complications of GSD. LT for GSD I and III was first reported, respectively, by Malatack et al in 198 and by Superina et al in 1989. We present five cases of GSD (four GSD Ia; one GSD III), which were treated by living donor liver transplantation (LDLT) in our institution. These patients were unresponsive to medical therapy or developed serious complications of GSD. In this study we investigate the outcome of these children after LDLT for GSD. PATIENTS AND METHODS

Repeated hypotensive episodes due to hepatic outflow obstruction during liver transplantation in adult patients

We report two cases of unusual repeated hypotension, decreased cardiac output, decreased mixed venous oxygen saturation, decreased central venous pressure, pulmonary artery pressure, and pulmonary wedge pressure after the completion of all vascular anastamoses of liver transplantation. These unstable hemodynamics appear to reflect a clinically relevant picture of hypovolemia. However, the real cause was partial hepatic outflow obstruction. The obstruction was suspected because hypotension was alleviated by elevating the full-sized liver graft ventrally and to the left. Doppler ultrasound examination confirmed that the flow velocity of the hepatic vein outflow was insufficient when the liver fell to its resting position in the right hepatic fossa. An additional side-to-side cavo-caval anastomosis resolved the problem in one patient, whereas the other required not only the additional anastomosis, but also application of a tissue expander filled with 770 mL normal saline beneath the liver to eliminate the obstruction. We emphasize that obstruction of the hepatic outflow causes only temporal hypovolemia because of a decrease of venous return and that treatment of this complication should be surgical intervention to relieve the obstruction. Blind resuscitation with fluids will not solve the problem and, in fact, may result in fluid overload with subsequent complications.

Plasma Exchange Therapy for Thrombotic Thrombocytopenic Purpura in Pediatric Patients With Liver Transplantation

PURPOSE Sporadic cases of thrombotic thrombocytopenic purpura (TTP) have been reported in bone marrow and solid organ transplant patients receiving cyclosporine (CsA). We reported our experience with TTP using plasma exchange (PE) therapy in patients with liver transplantation (OLT). METHODS Between March, 1993, and May, 2007, 400 patients underwent OLT, including 146 pediatric living-donor liver transplantation (LDLT). Four pediatric patients developed TTP after OLT: three were males and one female of mean age at the time of transplantation of 7.8 +/- 3.6 years. The four recipients had the following indications for OLT: two glycogen storage disease, one biliary atresia, and one fulminant hepatic failure. Four patients initially received triple drug immunosuppression consisting of CsA, azathioprine, and steroids. RESULTS Four (1%) patients developed TTP after OLT. All four patients were pediatric in the age group. The mean age at the time of TTP diagnosis was 8.0 +/- 3.2 years, with a mean postoperative interval to TTP of 78.8 +/- 114.2 days. The mean baseline platelet count was 7.0 +/- 7.1 x 10,000. The eventual platelet count was 21.1 +/- 20.8 x 10,000 after PE. These patients received PE 6.0 +/- 4.2. The mean baseline serum creatinine was 0.8 +/- 0.8 mg/dL. The mean peak serum creatinine was 2.3 +/- 2.3 mg/dL. The mean serum CsA level was 717.5 +/- 106.0 ng/mL before TTP diagnosis. Four patients were diagnosed by blood peripheral smears. The causes of TTP were CsA-associated in three patients and venoocclusive disease (VOD) in one patient. Three patients improved their platelet counts after PE therapy. Two patient changed from CsA to FK 506, one underwent reduced CsA dosage, and one stopped CsA. Three patients died of recurrent VOD, infection, and intrapulmonary hemorrhage. Only one patient survived. CONCLUSIONS The incidence of TTP in our series was lower. It only developed in pediatric patients. The causes of TTP were associated with CsA and/or VOD. The mortality was high after the TTP diagnosis. We concluded that TTP was a potentially fatal condition, but an early diagnosis with prompt institution of therapy with invasive PE therapy may reduce its mortal consequences.

Histopathology of the liver in pediatric patients following transplantation.

Recognition of rejection and other hepatic complications by needle biopsy plays a significant role in the management of liver allograft recipients. In this report, 22 pediatric patients (below 18 years old) were selected from the 37 liver transplants. Seven of the 22 cases have an uneventful posttransplant course. The most common cause of allograft injury in these patients appeared to be acute cellular rejection. It occurred in 7 (31.8%) of the 22 cases and was the primary process in 8 of the 25 episodes of liver dysfunction. Other etiologies, such as opportunistic viral infection (3 cases), biliary obstruction (2 cases), preservation injury (1 case), and vascular obstruction (1 case) were less common. Acute graft rejection causing liver dysfunction was associated with a mixed portal inflammation, destruction of the interlobular bile ducts, and varied degree of venous endotheliitis, followed by centrilobular hepatocyte necrosis. Chronic rejection was not seen in our pediatric cases. Cold ischemic injury causing transient graft dysfunction as seen in one of our patients demonstrated focal, limited areas of hepatocyte necrosis, mild centrilobular hepatocyte ballooning, and cholestasis without evidence of bile duct damage. More severe ischemic injury resulted from vascular complication causing diffuse hepatocyte necrosis was seen in one patient with hepatic vein thrombosis. The histologic patterns observed were not pathognomic; however, liver biopsies were helpful in suggesting the probable cause of liver dysfunction and in predicting subsequent allograft recovery when used in conjunction with clinical information, radiologic, and other laboratory tests.

Living-Donor Liver Transplantation in Taiwan

Living-donor liver transplantation (LDLT) is currently the only effective means to significantly increase the graft supply in societies where cadaveric donation is very limited, as in Taiwan. Since the Kaohsiung Chang Gung Memorial Hospital (CGMH) Liver Transplant Program commenced in 1993, as a continuation of the pioneering program in Linkou CGMH in 1984, we have performed a total of 94 liver transplants for pediatric and adult recipients, 57 of which were with grafts from living donors. Forty-eight of the LDLTs were left-side grafts and nine were right-side grafts. Donor hepatectomies were performed with minimal blood loss and no blood transfusions, which led to prompt recovery and eliminated the risk of transfusion-related disease. Multiple and smaller caliber vessels or ducts are major technical challenges in LDLT. Twelve grafts (21%) had multiple hepatic veins, 22 (39%) had multiple hepatic arteries, and 19 (33%) had multiple bile ducts. Significant technical complications included two hepatic outflow problems, four portal vein problems, and six biliary problems. There was no hospital mortality, but one patient developed septic shock after a radiological procedure and died 4 months after the transplant. The actual patient and graft survival rates were 98.2%. Careful patient selection, judicious preoperative evaluation, meticulous surgical techniques, and prompt detection and management of complications all contribute to optimizing outcomes in LDLT.

Imaging in Pediatric Liver Transplantation

In liver transplantation, the role of the imaging study in the evaluation of transplant candidacy is to define the conditions in which transplantation is contraindicated and to identify anatomic variations that may alter the surgical approach. Among pediatric recipients, the largest numbers of patients were suffering from biliary atresia, and metabolic diseases. Acquired and congenital vascular anomalies are usually associated with biliary atresia which may be hazardous to liver transplantation requiring a modification of standard surgical procedure. Therefore, confirmation of the patency of the vascular structure is the most essential prerequisite especially in living related liver transplantation. From June 17, 1994 to November 30, 1996, eleven living related liver transplantations were performed at Chang Gung Memorial Hospital, Kaohsiung Medical Center. The left liver or the left lateral segment of the liver was used as the graft. It is necessary to keep patency of the inflow and outflow of hepatic vessels and biliary trees of both donor and recipient. Both resected and remnant livers have to function well postoperatively. In order to achieve parenchyma dissection with minimal hepatic damage, various anatomical variations of the liver size, portal vein, hepatic veins and bile duct of the donor cannot be ignored. Therefore, the precise preoperative anatomical evaluation of the donor using various imaging modalities is mandatory for the safe partial liver transplantation. Ultrasound, computed tomography, magnetic resonance image and three dimensional computed tomographic cholangiography are the method of choice in demonstrating the anatomical structures. After the complex anatomical factors can be well evaluated we can assess the appropriateness and feasibility of the procedure that may correct problems during or after transplantation. Finally, noninvasive and safe examination procedures are our outmost concern and policy in doing this survey.