Teresa Diago

“Splenic artery steal syndrome” is a misnomer: The cause is portal hyperperfusion, not arterial siphon

Splenic artery embolization (SAE) improves hepatic artery (HA) flow in liver transplant (OLT) recipients with so‐called splenic artery steal syndrome. We propose that SAE actually improves HA flow by reducing the HA buffer response (HABR). Patient 1: On postoperative day (POD) 1, Doppler ultrasonography (US) showed patent vasculature with HA resistive index (RI) of 0.8. On POD 4, aminotransferases rose dramatically; his RI was 1.0 with no diastolic flow. Octreotide was begun, but on POD 5 US showed reverse diastolic HA flow with no signal in distal HA branches. After SAE, US showed markedly improved flow, RI was 0.6, diastolic flow in the main artery, and complete visualization of all distal branches. By POD 6, liver function had normalized. RI in the main HA is 0.76 at 2 months postsurgery. Patient 2: On POD 1, RI was 1.0. US showed worsening intrahepatic signal, with no signal in the intrahepatic branches and reversed diastolic flow despite good graft function. On POD 7, SAE improved the intrahepatic waveform and RI (from 1.0 to 0.72). Patient 3: Intraoperative reverse diastolic arterial flow persisted on PODs 1, 2, and 3, with progressive loss of US signal in peripheral HA branches. SAE on POD 4 improved the RI (0.86) and peripheral arterial branch signals. Patient 4: US on POD 1 showed good HA flow with a normal RI (0.7). A sudden waveform change on POD 2 with increasing RI (0.83) prompted SAE, after which the wave form normalized, with reconstitution of a normal diastolic flow (RI 0.68). In conclusion, these reports confirm the usefulness of SAE for poor HA flow but suggest that inflow steal was not the problem. Rather than producing an increase in arterial inflow, SAE worked by reducing portal flow and HABR, thereby reducing end‐organ outflow resistance. Evidence of this effect is the marked reduction of the RI after the SAE to 0.6, 0.72, 0.86, and 0.68, in patients 1‐4, respectively. SAE reduces excessive portal vein flow and thereby ameliorates an overactive HABR that can cause graft dysfunction and ultimately HA thrombosis. Liver Transpl 14:374–379, 2008.

Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small‐for‐size syndrome

The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100g/min) were 29 ± 12 (mean ± SD) and 74 ± 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7‐14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 ± 8 ml/100 g/min at 90 min and remained low out to POD 7‐14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome. Liver Transpl 15:1448–1457, 2009.

Measurement of CD4+ T-cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation.

Hashimoto K, Miller C, Hirose K, Diago T, Aucejo F, Quintini C, Eghtesad B, Corey R, Yerian L, Lopez R, Zein N, Fung J. Measurement of CD4+ T‐cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01169.x
© 2009 John Wiley & Sons A/S.

Duct-to-duct biliary reconstruction in patients with primary sclerosing cholangitis undergoing liver transplantation

BACKGROUND Reconstruction of biliary drainage after liver transplantation (LTx) in patients with primary sclerosing cholangitis (PSC) has been a matter of controversy. Over recent years, the traditional method of Roux-en-Y hepaticojejunostomy (RY) has been challenged by duct-to-duct (DD) biliary reconstruction. METHODS This study represents a retrospective review of biliary complications, patient and graft survival after LTx in PSC patients based on type of biliary reconstruction. Outcomes of DD reconstruction in this group of patients and non-PSC patients are compared. RESULTS A total of 53 primary LTx procedures were performed for PSC between August 2005 and July 2010. Seven patients were excluded because unexpected cholangiocarcinoma was found in the explants (n=3) or because they received partial livers (n=4). Biliary reconstruction was performed as DD in 18 patients and RY in 28 patients. There were no bile leaks. Anastomotic stricture occurred in two (11%) patients in the DD group and one (4%) in the RY group. Two (7%) patients in the RY group developed non-PSC intrahepatic strictures and one had recurrence of PSC. Rates of 1- and 3-year patient and graft survival in the RY and DD groups were 96.7% and 96.7%, and 100% and 94.5%, respectively. In a group of 34 randomly selected patients transplanted for a non-PSC diagnosis with DD reconstruction during the same period, the anastomotic stricture rate was 9% and 1- and 3-year patient and graft survival rates were 97.0% and 88.5%; differences were not significant. CONCLUSIONS Duct-to-duct biliary reconstruction at the time of LTx in selected PSC patients is both effective and safe, and shows outcomes comparable with those of RY reconstruction in these patients and those of DD reconstruction in non-PSC patients.

Split liver transplantation using Hemiliver graft in the MELD era: a single center experience in the United States.

Under the “sickest first” Model for End‐Stage Liver Disease (MELD) allocation, livers amenable to splitting are most often allocated to patients unsuitable for split liver transplantation (SLT). Our experience with SLT using hemilivers was reviewed. From April 2004 to June 2012, we used 25 lobar grafts (10 left lobes and 15 right lobes) for adult‐sized recipients. Twelve recipients were transplanted with primary offers, and 13 were transplanted with leftover grafts. Six grafts were shared with other centers. The data were compared with matched whole liver grafts (n = 121). In 92% of donors, the livers were split in situ. Hemiliver recipients with severe portal hypertension had a greater graft‐to‐recipient weight ratio than those without severe portal hypertension (1.96% vs. 1.40%, p < 0.05). Hemiliver recipients experienced biliary complications more frequently (32.0% vs. 10.7%, p = 0.01); however, the 5‐year graft survival for hemilivers was comparable to whole livers (80.0% vs. 81.5%, p = 0.43). The secondary recipients with leftover grafts did not have increased incidences of graft failure (p = 0.99) or surgical complications (p = 0.43) compared to the primary recipients. In conclusion, while routine application is still controversial due to various challenges, hemiliver SLT can achieve excellent outcomes under the MELD allocation.

Safety and effectiveness of renoportal bypass in patients with complete portal vein thrombosis: An analysis of 10 patients

The presence of portal vein thrombosis (PVT) is still considered by many transplantation centers to be an absolute contraindication to liver transplantation because of the technical difficulties that it can present and its association with a higher rate of patient morbidity and mortality. Renoportal bypass (RPB) can help to remove these barriers. This study describes our institutions experience with RPB through the description of a new and successful simplified surgical strategy, a patient and graft outcome analysis, intraoperative vascular flow measurements, and the use of splenic artery embolization (SAE) as an effective adjunct for treating sporadic cases of unrelieved portal hypertension. Between January 2004 and January 2013, 10 patients with grade 4 PVT underwent RPB. At the last follow‐up (42.2 ± 21.1 months), the patient and graft survival rates were 100%. Five patients (50%) experienced posttransplant ascites, and 2 of those underwent proximal SAE to modulate the liver inflow and overcome the ascites. Three patients (30%) experienced transient kidney injury in the early posttransplant period and were treated efficiently with medical therapy. The renoportal flows were close to the desirable 100 mL/100 g of liver tissue in all cases. The experience and data support RPB as a feasible and easily reproducible technique without the risks and technical challenges associated with the tedious dissection of a cavernous hilum. Liver Transpl 21:344–352, 2015.

Prognostic role of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma undergoing liver transplantation

Vascular endothelial growth factor (VEGF) is pivotal in the development of hepatocellular carcinoma (HCC). Studies have demonstrated the prognostic value of circulating VEGF levels in patients undergoing liver resection or locoregional therapy (LRT) for HCC. We investigated the significance of preoperative plasma VEGF levels in patients with HCC undergoing liver transplantation (LT) at a Western transplant center. Pre‐LT plasma VEGF levels were measured with an enzyme‐linked immunoassay for 164 patients with HCC undergoing LT. The preoperative plasma VEGF level was correlated with clinicopathological variables and overall and recurrence‐free post‐LT survival. A higher pre‐LT plasma VEGF level was significantly associated with pre‐LT LRT (P = 0.01), multiple tumors (P = 0.02), a total tumor diameter ≥ 5 cm (P = 0.01), bilobar tumor distribution (P = 0.03), tumor vascular invasion (VI; P < 0.001), and HCC beyond the Milan criteria (P < 0.001). Patients with a plasma VEGF level > 44 pg/mL had significantly worse overall and disease‐free survival than those with VEGF levels ≤ 44 pg/mL (P = 0.04 and P = 0.02, respectively). In a multivariate analysis, a plasma VEGF level > 44 pg/mL was independently associated with tumor VI (P < 0.001) and recurrence‐free survival (hazard ratio = 2.12, 95% confidence interval = 1.08‐4.14, P = 0.03). In conclusion, in patients with chronic end‐stage liver disease and HCC, a pre‐LT plasma VEGF level > 44 pg/mL may be a predictor of tumor VI and recurrence‐free post‐LT survival. Liver Transpl 21:101‐111, 2015.

Long-Term Follow-Up of Patients with Primary Sclerosing Cholangitis Undergoing Liver Transplantation with Duct-to-Duct Biliary

Background Reconstruction of biliary drainage after liver transplantation (LTx) in patients with primary sclerosing cholangitis (PSC) has been a matter of controversy. Over the recent years, the traditional method of Roux-en-Y hepaticojejunostomy (RY) has been challenged by duct-to-duct (DD) biliary reconstruction. The argument against DD reconstruction has been for potential increased risk of development of cholangiocarcinoma (CCA) in the bile duct remnant. Methods This is a retrospective review of biliary complications, graft and patient survival after LTx in PSC patients based on type of biliary reconstruction DD vs. RY. Results A total of 120 LTx for PSC were performed between 2005 and 2016. Twenty two patients were excluded because they received partial grafts. DD was done in 39 patients and 59 patients were reconstructed with RY. One-, 5-, and 10-year survival was similar between the two groups. Bile leak and biliary stricture was not significantly different between the 2 groups. Nine patients in DD group (23%), and 13 patients in RY group developed biliary strictures and all managed endoscopically or percutaneously. There was one case of anastomotic leak in each group. There was no case of CCA observed in these patients over the long period of follow-up. Conclusion DD biliary reconstruction at the time of LTx in selected PSC patients is both effective and safe, with comparable outcomes with those with RY reconstruction and NO increased risk for development of CCA in the bile duct remnant. Figure. No caption available. Figure. No caption available.

Su1021 De-Novo Autoimmune Hepatitis Following Liver Transplantation

Backgrounds/aims De-novo autoimmune hepatitis (AIH) after liver transplantation (LT) is rising. Yet there is scarcity of data on the characteristics and the long-term outcomes of this condition. The aim of this study is to investigate the clinical characteristics and long-term outcomes of patients with de novo AIH following LT.Methods Using transplant liver biopsy database, we identified all patients with de-novo AIH following LT at our institution between 2008 and 2013. Patients with hepatitis C virus infection were excluded. The diagnosis of de-novo AIH was made according to the classical and simplified criteria defined by the International Autoimmune Hepatitis Group. Clinical information was gathered from electronic medical records. H&E stained sections and histochemical stains from the liver biopsies revealed findings compatible with AIH. Results A total of nineteen patients with de-novo AIH were identified (58% female, median age of 46 years), with mean international autoimmune hepatitis score of 12.1. Underlying liver disease were primary sclerosing cholangitis (n=4), primary biliary cirrhosis (n=3), biliary atresia (n=3), drug induced liver failure (n=2), alcoholic hepatitis (n=2) and others (n=5). The interval period from the LT to diagnosis of de-novo AIH was 19.6 months (1.6-197.8), during which 11 (58%) patients developed at least one episode of acute cellular rejection prior to the diagnosis of de-novo AIH. All patients were successfully treated with corticosteroids and incremental dose in immunosuppression. All showed complete biochemical response to treatment but 9 (47.4%) patients relapsed upon tapering down corticosteroids. Patients were followed over 6.7 year (1.5-17) years post-LT. Eight (42%) patients progressed to cirrhosis of whom 3 (15%) patients expired and 2 (10%) required second LT due to complications of end stage liver disease. Conclusion The present study shows the long term clinical outcomes of the patients with de-novo AIH post-LT. Although most patients exhibit a good initial response to medical therapy, de-novo AIH post-LT is likely to recur and progress to liver cirrhosis. Therefore, we should consider denovo AIH in patients who show abnormal liver tests or graft dysfunction after LT.

Intrahepatic Blood Flow Redistribution After Temporary Occlusion of the Middle Hepatic Vein During Right Lobe Liver Donation: Report of a Case

INTRODUCTION One of the critical factors that influence graft function after live donor liver transplantation is the presence or absence of global or sectorial liver congestion. Many authors advocate for routine middle hepatic vein (MHV) reconstruction because it is often difficult to determine when the MHV or one of its major branches have functional significance. Predictive tests to assess hemodynamic and functional significance of the MHV and its tributaries are still under study. CASE REPORT We have described a novel intraoperative manipulation and Doppler ultrasonographic evaluation that led to the decision to include the MHV with the right lobe graft.