Chen Cl

Living Donor Liver Transplantation for Biliary Atresia: A Single-Center Experience with First 100 Cases

The aim of this study is to present our institutional experience in living donor liver transplantation (LDLT) as a treatment for end‐stage liver disease in children with biliary atresia (BA). A retrospective review of transplant records was performed. One hundred BA patients (52 males and 48 females) underwent LDLT. The mean follow‐up period was 85.5 months. The mean age was 2.4 years. The mean preoperative weight, height, and computed GFR were 12.2 kg, 82.5 cm, and 116.4 ml/min/1.73 m2, respectively. Twenty‐seven patients were below 1 year of age, and 49 patients were below 10 kg at the time of transplantation. Ninety‐six had had previous Kasai operation prior to transplant. The mean recipient operative time was 628 min. The mean recipient intraoperative blood loss was 176 ml. Thirty‐five did not require blood or blood component transfusion. The left lateral segment (64) was the most common type of graft used. There were 27 operative complications which included 3 reoperations for postoperative bleeding, 9 portal vein, 4 hepatic vein, 4 hepatic artery, and 7 biliary complications. There was one in‐hospital mortality and one retransplantation. The overall rejection rate was 20%. The overall mortality rate was 3%. The 6‐month, 1‐year and 5‐year actual recipient survival rates were 99%, 98% and 98%, respectively.

Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.

This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti‐HBc(+) donors, and another 30 received grafts from anti‐HBc(−) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti‐HBc(+) grafts for about 2 years. Forty‐seven (78%) recipients achieved high levels of anti‐HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti‐HBc(−) graft and another received an anti‐HBc(+) graft. Both recipients were in the lower anti‐HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow‐up period was 51 months in recipients with anti‐HBc(−) grafts and 57 months in those with anti‐HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti‐HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.

Vascular Stents in the Management of Portal Venous Complications in Living Donor Liver Transplantation

To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 PV occlusions and 6 stenoses) recipients (age range, 8 months–59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long‐term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow‐up was 12 months (range, 3–24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.

Liver graft-to-recipient spleen size ratio as a novel predictor of portal hyperperfusion syndrome in living donor liver transplantation.

Portal hyperperfusion in a small‐size liver graft is one cause of posttransplant graft dysfunction. We retrospectively analyzed the potential risk factors predicting the development of portal hyperperfusion in 43 adult living donor liver transplantation recipients. The following were evaluated: age, body weight, native liver disease, spleen size, graft size, graft‐to‐recipient weight ratio (GRWR), total portal flow, recipient portal venous flow per 100 g graft weight (RPVF), graft‐to‐recipient spleen size ratio (GRSSR) and portosystemic shunting. Spleen size was directly proportional to the total portal flow (p = 0.001) and RPVF (p = 0.014). Graft hyperperfusion (RPVF flow >250 mL/min/100 g graft) was seen in eight recipients. If the GRSSR was <0.6, 5 of 11 cases were found to have graft hyperperfusion (p = 0.017). The presence of portosystemic shunting was significant in decreasing excessive RPVF (p = 0.059). A decrease in portal flow in the hyperperfused grafts was achieved by intraoperative splenic artery ligation or splenectomy. Spleen size is a major factor contributing to portal flow after transplant. The GRSSR is associated with posttransplant graft hyperperfusion at a ratio of <0.6.

Liver graft regeneration in right lobe adult living donor liver transplantation.

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital‐Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight‐to‐recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty‐five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 ± 12.6% (range, 58–151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

The Fas and Fas ligand pathways in liver allograft tolerance

The Fas and Fas ligand (Fas/FasL) pathways may play a central role in cytotoxicity or immunoregulation in liver transplantation. Here, in an attempt to examine the role of Fas/FasL on drug‐free tolerance, we measured mRNA levels of Fas/FasL in livers by reverse transcriptase‐polymerase chain reaction (RT‐PCR), and also protein levels of Fas/FasL in livers by immunohistochemistry and in serum by dot blot assay. PVG recipients bearing DA livers showed serious rejection between post‐operative (POD) days 7 and 14 , but this rejection was naturally overcome without any immunosuppression. Fas gene and protein products were expressed on almost every cell in livers taken from naive rats, and at any time point in both syngeneic and allogeneic orthotopic liver transplantation (OLT) rats. In contrast, FasL mRNA in DA livers was detectable at POD 2, peaked at POD 14, and declined at POD 63 in allogeneic OLT (DA‐PVG). Although the FasL gene was detectable in isografts at POD 14, its expression was much lower than in allografts. The time course and localization of FasL expression indicated that the expression of FasL gradually switched from infiltrating cells to hepatocytes when the rejection was naturally overcome and tolerance was induced in this OLT model. Soluble Fas could constitutively be detected at any time point in the serum of the tolerogenic OLT (DA‐PVG) rats and was not diminished during the rejection phase. Soluble FasL peaked at POD 14 in allogeneic OLT, while sFasL was significantly lower in the serum of normal and syngeneic OLT rats. These findings suggest that the Fas and FasL pathways, including soluble forms, may contribute to the control of the immune response in this drug‐free tolerance OLT model.

Major hepatic resection may suppress the growth of tumours remaining in the residual liver

Little is known as to how hepatectomy is associated with the growth of hepatic tumours, which may reside in the remaining liver after curative resection for hepatocellular carcinoma. Using an intra-hepatic tumour implantation model in rats, the effects of hepatectomy on tumour growth in the remaining liver were investigated. On post-operative day 7, the tumour weight in the remaining liver following 30% hepatectomy was 0.321 ± 0.058 g (mean ± SD) which was significantly greater than that (0.245 ± 0.040 g) in sham operations (P < 0.05). However, the tumour weight (0.156 ± 0.067 g) in the remaining liver following 60% hepatectomy was significantly lower than that in sham animals (P < 0.005). The number of TdT-mediated dUTP nick-end labelling (TUNEL) positive tumour cells was significantly increased in 60% hepatectomy as compared with the sham and 30% hepatectomy group. The mRNA expression of TGF-β1, TNF-α and Fas in the tumour portion of 60% hepatectomy, was higher than that in 30% hepatectomy group. Plasma levels of TGF-β1 were inversely correlated with intra-hepatic tumour weights. These results suggest that major hepatic resection may lead to an increased induction of apoptosis for the remaining hepatic tumour.

Central nervous system manifestations of neonatal lupus: a systematic review

Neonatal lupus is a rare and acquired autoimmune disease. Central nervous system abnormalities are potential manifestations in neonatal lupus. Through a systematic literature review, we analyzed the clinical features of previously reported neonatal lupus cases where central nervous system abnormalities had been identified. Most reported neonatal lupus patients with central nervous system involvement were neuroimaging-determined and asymptomatic. Only seven neonatal lupus cases were identified as having a symptomatic central nervous system abnormality which caused physical disability or required neurosurgery. A high percentage of these neurosymptomatic neonatal lupus patients had experienced a transient cutaneous skin rash and had no maternal history of autoimmune disease before pregnancy.

Diagnosis and Interventional Radiological Treatment of Vascular and Biliary Complications After Liver Transplantation in Children With Biliary Atresia

OBJECTIVE Early diagnosis and appropriate management of vascular and biliary complications after living donor liver transplantation (LDLT) result in longer survival. We report our institutional experience regarding radiological management of these complications among patients with biliary atresia (BA) who underwent LDLT. METHODS We analyzed the records of 116 children. All patients underwent Doppler ultrasound (US) at operation, daily for the first 2 postoperative weeks, and when necessary thereafter. After primary evaluation using US, the definite diagnosis of postoperative complication was confirmed using computed tomography, magnetic resonance imaging, and/or operation. RESULTS There were 61 boys and 55 girls. The overall mean age was 2.69 years. The overall mean preoperative weight and height were 13.06 kg and 83.79 cm, respectively. There were 28 (24.13%) biliary and vascular complications. These were cases of biliary stricture (n = 5), bile leakage (n = 3), hepatic artery stenosis (n = 6), hepatic vein stenosis (n = 4), and portal vein thrombosis (n = 17). The diagnostic accuracy of US in detecting biliary complication, hepatic artery stenosis, hepatic venous stenosis, and portal vein thrombosis was 95.69%, 97.41%, 100%, and 100%, respectively. US in combination with multiple imaging modalities and clinical suspicion resulted in 100% diagnostic accuracy. Percutaneous transhepatic cholangiography, thrombolysis, balloon angioplasty, and stent placement were performed for the complications noted. There was an early mortality due to multiple-organ failure after failed radiological invention and subsequent surgical management. CONCLUSIONS Doppler US is accurate in detecting postoperative complications after pediatric LDLT for BA. Radiological interventions for vascular and biliary complications are effective and safe alternatives to reconstructive surgery.

International sharing of split liver grafts in asia : initial experience

The donor shortage problem is particularly serious in Asia and has markedly limited progress in liver transplantation. The increasing demand has, in fact, made it necessary to resort to living donor liver transplantation in both pediatric and adult recipients. Nevertheless, expanding the use of split liver allografts is yet another option to increase the supply. This has a wide potential application on a regional level because most liver transplant programs are still small and may have limited resources in terms of being able to do two transplants in one sitting. The first experience of overseas sharing of split liver grafts in Asia took place in January 1999. The graft was from a 35‐yr‐old donor from Kaohsiung, Taiwan, who sustained irreversible brain damage in a vehicular accident and had optimal conditions for multiorgan donation. The liver was split ex vivo and the left lateral segment was given to a 3‐yr‐old girl with biliary atresia at the Chang Gung Memorial Hospital. The extended right lobe split graft was transported to Hong Kong and transplanted into a 51‐yr‐old male patient with end‐stage hepatitis C cirrhosis who was then in a state of acute failure with hepatorenal syndrome. Graft function was excellent in both recipients and the patient from Taiwan was discharged without any complications. Unfortunately, the Hong Kong recipient developed a cerebrovascular accident and required a reoperation for bile leakage from the cut surface of the liver in the early postoperative period. He has made a steady recovery since then; graft function has remained good and his kidneys have recovered. Both patients are currently alive and well 11 months post‐transplant. 
This initial experience of overseas sharing of split liver grafts in Asia demonstrates its feasibility. It has a potentially wide applicability and could lead to the establishment of a formal organ‐sharing network in the region. Established competence and mutual trust among the participating liver transplant teams would be essential in perpetuating such a graft‐multiplying strategy on an organized basis.