As part of intracellular copper trafficking pathways, the human copper chaperone Hah1 delivers Cu+ to the Wilson's Disease Protein (WDP) via weak and dynamic protein-protein interactions. WDP contains six homologous metal binding domains (MBDs) connected by flexible linkers, and these MBDs all can receive Cu+ from Hah1. The functional roles of the MBD multiplicity in Cu+ trafficking are not well understood. Building on our previous study of the dynamic interactions between Hah1 and the isolated 4th MBD of WDP, here we study how Hah1 interacts with MBD34, a double-domain WDP construct, using single-molecule fluorescence resonance energy transfer (smFRET) combined with vesicle trapping. By alternating the positions of the smFRET donor and acceptor, we systematically probed Hah1-MBD3, Hah1-MBD4, and MBD3-MBD4 interaction dynamics within the multi-domain system. We found that the two interconverting interaction geometries were conserved in both intermolecular Hah1-MBD and intramolecular MBD-MBD interactions. The Hah1-MBD interactions within MBD34 are stabilized by an order of magnitude relative to the isolated single-MBDs, and thermodynamic and kinetic evidences suggest that Hah1 can interact with both MBDs simultaneously. The enhanced interaction stability of Hah1 with the multi-MBD system, the dynamic intramolecular MBD-MBD interactions, and the ability of Hah1 to interact with multiple MBDs simultaneously suggest an efficient and versatile mechanism for the Hah1-to-WDP pathway to transport Cu+.

PURPOSE The aim of this study was to evaluate predictive factors for persistent splenomegaly and hypersplenism after living donor liver transplantation (LDLT). PATIENTS AND METHODS From January 2008 to June 2010, 159 adult patients (116 males and 43 females) who underwent living donor liver transplantation (LDLT) had pre- and post-LDLT computed tomography angiography and survived more than 6 months. Patients with post-LDLT portal vein stenosis were excluded from this study. We analyzed the impact for persistent splenomegaly and hypersplenism after LDLT of pre-LDLT spleen volume, main portal vein (PV) size, coronary vein (CV) size and platelet levels. RESULTS While 38 patients displayed splenomegaly, 121 showed normal spleen volumes at 6 months after LDLT (LDLT). There were 119 thrombocytopenic versus 40 normal platelet patients at 6 months post-LDLT. The persistent splenomegaly patients showed significantly larger pre-LDLT spleen volume, larger PV and CV sizes as well as lower platelet levels before (×10,000/mL) and 1 month after LDLT (×10,000/mL). Multiple logistic regression analysis showed spleen volume and platelet count at 1 month posttransplant to be the only variables associated with persistent splenomegaly at 6 months post. Persistent thrombocytopenia at 6 months post-LDLT was associated with significantly larger pre-LDLT spleen volume, larger CV size, and lower platelet levels including P0 and P1 m. Multiple logistic regression analysis showed that platelet count at 1 week and at 1 month post-LDLT were the variables associated with persistent thrombocytopenia at 6 months post-LDLT. CONCLUSION Spleen volume and platelet levels at 1 month after LDLT may predict persistent splenomegaly at 6 months post-LDLT. The predictive factors for hypersplenism at 6 months post-LDLT may be platelet levels at 1 week and at 1 month post-LDLT.

Choledochal cysts are not rare in East Asia. The classic symptoms of these cysts are intermittent abdominal pain, jaundice, and a right upper quadrant abdominal mass. The authors report the case of an infant with a choledochal cyst presenting with intracranial hemorrhage. This 2-month-old girl with a partial coma presented at the authors' hospital. A brain CT scan revealed right-sided subdural hemorrhage. The routine preoperative survey found coagulopathy. After correcting the bleeding disorder, an emergency craniectomy was performed. Further examination found a choledochal cyst during abdominal ultrasonography and CT. Choledochal cysts are a cause of neonatal cholestasis but rarely produce vitamin K deficiency bleeding.

For pediatric living donor liver transplantation, portal vein complications cause significant morbidity and graft failure. Routine intra-operative Doppler ultrasound is performed after graft reperfusion to evaluate the flow of portal vein. This retrospective study reviewed 65 children who had undergone living donor liver transplantation. Seven patients were detected with suboptimal portal vein flow velocity following vascular reconstruction and abdominal closure. They underwent immediate on-table interventions to improve the portal vein flow. Both surgical and endovascular modalities were employed, namely, graft re-positioning, collateral shunt ligation, thrombectomy, revision of anastomosis, inferior mesenteric vein cannulation, and endovascular stenting. The ultrasonographic follow-up assessment for all seven patients demonstrated patent portal vein and satisfactory flow. We reviewed our experience on the different modalities and proposed an approach for our future intra-operative management to improve portal vein flow at the time of liver transplantation.

In living donor liver transplantation (LDLT), the essential aims are to provide an adequate graft volume to the recipient and to keep a sufficient remnant liver volume in the donor. In some instances, these aims cannot be met by a single donor and LDLT using dual grafts from two donors is a good solution. From 2002 to 2009, five recipients in our hospital received dual graft LDLT. Two recipients received one right lobe and one left lobe grafts; the other three received two left lobe grafts. The mean final liver regeneration rate was 91.2%. Left lobe graft atrophy in the long term was observed in recipients who received a right and a left lobe grafts. The initial bigger volume graft in all recipients was noted to have better regeneration than the smaller volume grafts. Portal flow and bilateral grafts volume size discrepancy were considered as two major factors influencing graft regeneration in this study. We also noted that the initial graft volume correlated with portal flow in the separate grafts and finally contribute to individual graft regeneration. Because of compensatory hypertrophy of the other graft, recipients who experienced atrophy of one graft did not show signs of liver dysfunction.

AIM The aim of this study was to evaluate portal vein stenosis (PVS) in pediatric liver transplantation (PLT) using Doppler ultrasound (DUS) before and after interventional management for hemodynamic changes. MATERIALS AND METHODS From 2000 to 2010, we encountered 11 PVS cases among 180 PLT that were evaluated using DUS and computed tomography (CT) angiography (CTA); all underwent portal stenting. DUS was used to monitor portal hemodynamics. For the diagnosis of PVS, we investigated multiple parameters including stenotic size (SS), stenotic ratio (SR)(SR [%]= PRE-SS/PRE [PRE = stenotic size]), portal flow velocity ratio (VR)(VR = VS/PRE [PRE = velocity at prestenotic site; VS = peak velocity at stenotic site]), spleen size, and platelet count. RESULTS The incidence of PVS was 5.6%(11/180). The PV was 2.5 mm using DUS and 2.7 mm using CTA. The average SR was 65% fitting the criterion. Low prestenotic portal flow <12 cm/sec and high peak velocity in the stenotic segment (up to 147 cm/sec) were observed in 6 cases. The VR value was high at 7.5:1 and there was splenomegaly with thrombocytopenia. After portal vein stenting, hyperperfusion occurred might after reopening the stenosis: the flow increased to an average of 34 cm/sec and then flow decreased slowly to a stable level 2 weeks later. The size of the spleen decreased from 17 to 12 cm and the thrombocytopenia also improved with platelet counts increasing from 67 × 10(3) to 178 × 10(3)/μl at 2 months follow-up. The changes in portal flow, portal vein size, spleen size, and platelet count were significant (P <.05). CONCLUSION PVS is diagnosed using DUS by increased intrahepatic PV dilatation, peak flow at the stenotic site, discrepant VR. Early portal stenting showed a better prognosis. DUS is essential and effective for hemodynamic monitoring and management of PVS.

BACKGROUND Biliary complications are a major problem in pediatric liver transplantation. The aim of this study was to evaluate the management and outcomes of biliary complication after pediatric living donor liver transplantation (LDLT). METHODS From 1994 to 2010, 157 pediatric LDLT due to biliary atresia were performed in our center. Doppler ultrasound was initially performed daily for 2 weeks postoperatively to evaluate biliary and vascular complications. Computed tomography and or magnetic resonance cholangiography were performed when complications were suspected. They were treated using radiological or surgical interventions. RESULTS Among the 157 cases, we observed 10 (6.3%) biliary complications, which were divided into three groups: bile leakage (n = 3); biliary stricture without vascular complication (n = 4); and biliary stricture with vascular complication (n = 3). The three cases bile leakages recovered after interventional procedures. The seven biliary strictures underwent percutaneous transhepatic cholangial drainage (PTCD). All cases without vascular complications were completely cured after PTCD or a subsequent surgical re-anastomosis. In the vascular complication group, early recorrection of the HA occlusion with successful PTCD treatment were performed in two cases, but one other case with diffuse ischemic biliary destruction had a poor result. CONCLUSION Successful interventional radiographic approaches are effective for anastomotic biliary complications but with poor results in diffuse ischemic biliary destruction.

BACKGROUND Hepatocellular carcinoma (HCC) is the leading malignant tumor in Taiwan. The majority of HCC patients are diagnosed in late stages and therefore in eligible for potentially curative treatments. Locoregional therapy has been advocated as an effective treatment for patients with advanced HCCs. PURPOSE The aim of this study was to evaluate the outcomes of HCC downstaged patients after locoregional therapy to allow eligibility for liver transplantation. METHODS AND MATERIALS From January 2004 to June 2010, 161 patients with HCCs underwent liver transplantation including 51 (31.6%) who exceeded the University of California-San Francisco (UCSF) who had undergone successful locoregional therapy to be downstaged within these criteria. Among the downstaged patients, 48 (94.1%) underwent transarterial embolization; 7 (13.8%), percutaneous ethanol injection; 24 (47.1%), radiofrequency ablation; 15 (29.4%), surgical resection, and 34 (66.7%), combined treatment. RESULTS The overall 1- and 5-year survival rates of all HCC patients (n = 161) were 93.2% and 80.5%. The overall 1- and 5-year survival rates of downstaged (n = 51) versus non-downstaged (n = 110) subjects were 94.1% versus 83.7% and 92.7% versus 78.9%, respectively (P =.727). There are 15 (9.2%) HCC recurrences. The overall 1- and 5-year tumor-free rates of all HCC patients were 94.8% and 87.2%. The overall 1- and 5-year tumor-free rates between downstaged versus non-downstaged patients were 93.9% and 90.1% versus 95.2% and 86.0%, respectively (P =.812). CONCLUSION Patients with advanced HCC exceeding the UCSF/Milan criteria can be downstaged to fit the criteria using locoregional therapy. Importantly, successfully downstaged patients who are transplanted show excellent tumor-free and overall survival rates, similar to fit-criteria group.

OBJECTIVE The purpose of this study was to evaluate the image quality and diagnostic accuracy of postgadolinium complex of diethylenetriaminepentaacetic acid (GD-DTPA)-enhanced magnetic resonance cholangiography (MRC) in donor selection. MATERIALS AND METHODS Donors (n = 228) with both preoperative MRC and intraoperative cholangiography (IOC) were enrolled in this study. MRC pre- and post-GD-DTPA enhancement were performed using 1.5-T magnetic resonance imaging. The signal-to-noise ratio (SNR) of liver parenchyma and contrast-to-noise ratio of bile duct, as well as the contrast between bile duct and liver parenchyma, were calculated. The biliary anatomy correlation with the IOC during hepatectomy and patient prognosis were also evaluated. RESULTS Quantitative results of the SNR of the liver parenchyma post-GD-DTPA were statistically significantly lower than preenhanced MRC (2.69 times reduced from the preenhanced MRC). The contrast of the bile duct and liver parenchyma in post-GD-DTPA were significantly higher than the preenhancement MRC. The anatomic diagnostic accuracy rate of post-GD-DTPA MRC was 92.9%. The sensitivity and specificity of GD-PTPA MRC were 85% and 96%, respectively. GD-DTPA-enhanced MRC has higher accuracy than the preenhanced MRC (92.9% vs 75%). The concurrence between GD-DTPA-enhanced MRC and IOC were commendable (kappa = 0.9). The posttransplant biliary complication rate was 5.5%, and the 3-year survival rate was 91.2% in the recipients. CONCLUSION GD-DTPA, a paramagnetic metal, can shorten the T1 and T2 relaxation values of surrounding protons. This decreases the signal of the liver parenchyma and brightens the biliary anatomy. It can improve the image quality of MRC and increase the diagnostic accuracy of the biliary tract classification. It is mandatory in the "donor and recipient surgery during the LDLT".

Chen H-L, Tsang LL-C, Concejero AM, Huang T-L, Chen T-Y, Ou H-Y, Yu C-Y, Chen C-L, Cheng Y-F. Segmental regeneration in right-lobe liver grafts in adult living donor liver transplant. Clin Transplant 2012 DOI: 10.1111/j.1399-0012.2011.01587.x. © 2012 John Wiley & Sons A/S. Abstract:  Our aim is to evaluate the relationship and impact of right-lobe (RL) liver grafts procured with or without the middle hepatic vein (MHV) trunk and MHV tributary reconstruction on segmental regeneration of these grafts in adult living donor liver transplantation (ALDLT). Patients underwent primary ALDLT using a RL liver graft were divided into three groups according to graft type: with MHV tributary reconstruction (group I), without MHV tributary reconstruction (group II), and with inclusion of the MHV trunk (group III). The overall graft volume and the volumes of the anterior and posterior segments of the grafts six months post-transplant, evaluated using computed tomography, were calculated as the regeneration indices. Optimal regeneration of the RL liver graft was achieved in the three groups of patients. There was no significant difference in the regeneration indices between groups I (149.4%) and III (143.6%). However, in group II (112.4%) without MHV or tributary reconstruction, the anterior regenerative index was lower than the other two groups and exhibited transient prolonged hyperbilirubinemia. Segmental graft regeneration is maximized by adequate venous drainage. Inclusion of the MHV trunk or MHV tributary reconstruction influences segmental liver regeneration and preclude transient hyperbilirubinemia in the early post-liver transplant phase.