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1.  Recipient and donor thrombophilia and the risk of portal venous thrombosis and hepatic artery thrombosis in liver recipients 
BMC Gastroenterology  2011;11:130.
Vascular complications, such as HAT, are an important cause of graft loss and recipient mortality. We aimed to characterize post-transplant thrombotic events in a cohort of liver transplant recipients, and identify independent risk factors for these complications.
We conducted a thrombophilic study of 293 orthotopic liver transplants performed in the Digestive Surgery Department of the 12 de Octubre Hospital (Madrid, Spain) between January 2001 and December 2006.
The most frequent post-transplant thrombotic events were HAT (9%) and PVT (1.7%). The one variable associated with post-transplant thrombotic event was a high fibrinogen level in the global cohort of liver transplantation. But toxicity as event post-OLT has been associated with post-transplant thrombotic event in the retrospective group and high fibrinogen level and low protein C levels were associated post-transplant thrombotic event in the prospective group. Liver disease relapse (HR 6.609, p < 0.001), high levels of FVIII (HR 1.008, p = 0.019)) and low levels of antithrombin (HR 0.946, p < 0.001) were associated with poor overall survival (OS).
In conclusion, high fibrinogen and decreased protein C levels were associated with allograft thrombosis. Further studies are required in order to assess the clinical relevance of these parameters in prospective studies and to study the effect of anticoagulation prophylaxis in this group of risk.
PMCID: PMC3287260  PMID: 22123067
2.  Liver Transplantation in the Presence of Old Portal Vein Thrombosis 
Background: Portal vein thrombosis (PVT) has been mentioned as a potential obstacle to liver transplantation (LTx).
Objective: To review the impact of PVT on orthotopic liver transplant (OLT) outcome.
Method: Between January 2006 and April 2009, 440 OLT were performed in Shiraz Transplant Unit of whom, 35 (7.9%) cases had old PVT with recanalization. Data were retrospectively collected regarding the demographics, indication for OLT, Child-Turgot-Pugh classification, pre-transplant diagnosis of PVT, perioperative course and managements, relapse of PVT, early post-operative mortality and morbidity. All patients received liver from deceased donors, underwent thrombendvenectomy with end-to-end anastomosis without interposition graft and evaluated daily for 5 days and thereafter, biweekly by duplex sonography during the follow-up period for 2 months. They were treated by therapeutic doses of heparin followed by warfarin to maintain an INR of 2–2.5.
Results: The causes of end-stage liver disease were hepatitis B in 11, cryptogenic cirrhosis in 11, primary sclerosing cholangitis in 5 and other causes in 8 recipients. Extension of thrombosis was through confluence of superior mesenteric and splenic vein in 32 and to superior mesenteric vein in 3 patients. The mean±SD operation time was 7.2±1.5 hrs. The mean±SD transfusion requirement was 5.4±2.8 units of packed cells. The mean±SD duration of hospital stay in these patients was 17.7±10.9 days. Eight patients died; 1 developed early in-hospital PVT, 1 had hepatic vein thrombosis, and 1 died of in-hospital ischemic cerebrovascular accident, despite a full anticoagulant therapy. The mean±SD follow-up period for those 28 patients discharged from hospital was 16.6±7.9 months; none of them developed relapse of PVT. The overall mortality and morbidity was 28% and 32%, respectively. There was no relapse of PVT in the other patients.
Conclusion: The presence of PVT at the time of OLT is not a contraindication for the operation but those with PVT have a more difficult surgery, develop more postoperative complications, and experience a higher in-hospital mortality.
PMCID: PMC4089218  PMID: 25013563
Portal vein thrombosis; liver transplantationl; Iran
3.  Orthotopic Liver Transplantation in High-Risk Patients 
Transplantation  1998;65(4):499-504.
One of the most controversial areas in patient selection and donor allocation is the high-risk patient. Risk factors for mortality and major infectious morbidity were prospectively analyzed in consecutive United States veterans undergoing liver transplantation under primary tacrolimus-based immunosuppression.
Twenty-eight pre-liver transplant, operative, and posttransplant risk factors were examined univariately and multivariately in 140 consecutive liver transplants in 130 veterans (98% male; mean age, 47.3 years).
Eighty-two percent of the patients had post-necrotic cirrhosis due to viral hepatitis or ethanol (20% ethanol alone), and only 12% had cholestatic liver disease. Ninety-eight percent of the patients were hospitalized at the time of transplantation (66% United Network for Organ Sharing [UNOS] 2, 32% UNOS 1). Major bacterial infection, posttransplant dialysis, additional immunosuppression, readmission to intensive care unit (P=0.0001 for all), major fungal infection, posttransplant abdominal surgery, posttransplant intensive care unit stay length of stay (P<0.005 for all), donor age, pretransplant dialysis, and creatinine (P<0.05 for all) were significantly associated with mortality by univariate analysis. Underlying liver disease, cytomegalovirus infection and disease, portal vein thrombosis, UNOS status, Childs-Pugh score, patient age, pretransplant bilirubin, ischemia time, and operative blood loss were not significant predictors of mortality. Patients with hepatitis C (HCV) and recurrent HCV had a trend towards higher mortality (P=0.18). By multivariate analysis, donor age, any major infection, additional immunosuppression, post-transplant dialysis, and subsequent transplantation were significant independent predictors of mortality (P<0.05). Major infectious morbidity was associated with HCV recurrence (P=0.003), posttransplant dialysis (P=0.001), pretransplant creatinine, donor age, median blood loss, intensive care unit length of stay, additional immunosuppression, and biopsy-proven rejection (P<0.05 for all). By multivariate analysis, intensive care unit length of stay and additional immunosuppression were significant independent predictors of infectious morbidity (P<0.03). HCV recurrence was of borderline significance (P=0.07).
Biologic and physiologic parameters appear to be more powerful predictors of mortality and morbidity after liver transplantation. Both donor and recipient variables need to be considered for early and late outcome analysis and risk assessment modeling.
PMCID: PMC2972634  PMID: 9500623
4.  Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation 
Gut  2005;54(5):691-697.
Background and aims: Splanchnic vein thrombosis is a significant source of complications in candidates for liver transplantation. The aims of this study were: (a) to determine the prevalence of and risk factors for splanchnic vein thrombosis in cirrhotic patients awaiting transplantation and (b) to assess the usefulness of anticoagulation.
Methods: A total of 251 cirrhotic patients listed for transplantation were analysed. All underwent systematic screening for thrombosis with Doppler ultrasonography. During the second period of the study, all patients with thrombosis received anticoagulation up to transplantation while during the first period none had received anticoagulation.
Results: The incidence of splanchnic vein thrombosis at evaluation was 8.4%. Seventeen additional patients (7.4%) developed de novo thrombosis after evaluation. Independent risk factors for thrombosis were low platelet count (77.4 (36.3) v 111.6 (69.2) 109/l; p = 0.001), a past history of variceal bleeding (47.4% v 29.1%; p = 0.003), and a prolonged interval from listing to transplantation (8.5 (6.8) v 4.8 (4.4) months; p = 0.002). The proportion of partial or complete recanalisation was significantly higher in those who received (8/19) than in those who did not receive (0/10, p = 0.002) anticoagulation. Survival was significantly lower in those who had complete portal vein thrombosis at the time of surgery (p = 0.04).
Conclusion: These results support a systematic screening for splanchnic vein thrombosis in patients awaiting transplantation. They suggest that in these patients, anticoagulation is safe and has a significant impact on recanalisation as well as prevention of extension of thrombosis.
PMCID: PMC1774501  PMID: 15831918
portal vein thrombosis; cirrhosis; portal hypertension; vitamin K antagonists; liver transplantation
5.  A High Incidence of Native Portal Vein Thrombosis in Veterans Undergoing Liver Transplantation 
The Journal of surgical research  1996;60(2):333-338.
The incidence of native portal vein thrombosis (PVT) in liver transplant recipients has been reported to range from 2.1 to 13.8%. We have identified an inordinately high incidence of PVT in a consecutive series of U.S. veterans receiving liver transplants. Between October 1989 and February 1994, 88 consecutive U.S. veterans received 99 orthotopic liver transplants under primary Tacrolimus (Prograf, formerly FK506) based immunosuppression. A number of clinical features were examined in an effort to identify risk factors for PVT and outcome was compared to patients without PVT. Native PVT was present in 23/88 (26%) patients. All of these patients were male U.S. veterans with a mean age of 47 years. When compared to the 65 patients without PVT, we found no significant difference with respect to underlying liver disease, age, Childs-Pugh score (mean = 12), UNOS status as defined prior to April 1995 (95% UNOS 3 or 4), previous abdominal surgery, or liver volume. Median blood loss for patients with PVT (21 units of packed red blood cells) was greater than for those without PVT (14 units, P = 0.04). Portal thrombectomy was performed in 11 patients, 11 patients required mesoportal jump grafts, and 1 patient had an interposition graft. Standard veno-venous bypass was used in 10 patients with single bypass utilized for the remainder. Actuarial patient survival for all patients at 1, 2, and 4 years was 88, 85, and 79%, respectively. There was no significant difference in patients with or without PVT. Patients with PVT had poorer graft survival than patients without PVT (86% vs 65%, 1 year; 81% vs 65%, 2 years; 81% vs 61%, 4 years; P = 0.03); however, this was not related to technical problems with the portal venous inflow. PVT occurred in 26% of U.S. veterans undergoing liver transplantation. These patients had significantly higher operative blood loss and poorer graft survival. The high incidence of postnecrotic cirrhosis in a predominantly male group of patients with advanced disease, as is evident by the high mean Childs-Pugh score and UNOS status, perhaps accounts for our observations.
PMCID: PMC2950617  PMID: 8598664
6.  Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation 
Percutaneous transhepatic portal access avoids surgery, but is rarely associated with bleeding or portal venous thrombosis. We herein report our large, single-center experience of percutaneous islet implantation, and evaluate risk factors of portal vein thrombosis and graft function.
Prospective data was collected on 268 intraportal islet transplants (122 subjects). A portal venous Doppler ultrasound was obtained on Days 1 and 7 days posttransplant.
Therapeutic heparinization, complete ablation of the portal catheter tract with Avitene paste, and limiting packed cell volume to < 5 ml completely prevented any portal thrombosis in the most recent 101 islet transplant procedures over the past 5 years. In the previous cumulative experience, partial thrombosis did not affect islet function. Standard liver volume correlated negatively (r=−0.257, P<0.001), and packed cell volume correlated positively with portal pressure rise (r=0.463, P<0.001). Overall, partial portal thrombosis occurred after 10 procedures (overall incidence 3.7%, most recent 101 patient incidence 0%). There were no cases of complete thrombosis, and no patient developed sequelae of portal hypertension.
In conclusion, portal thrombosis is a preventable complication in clinical islet transplantation, provided therapeutic anticoagulation is maintained, and packed cell volume is limited to <5 ml.
PMCID: PMC3226916  PMID: 21883914
Islet transplantation; risk factors; portal vein thrombosis; standard liver volume
7.  Blood loss, predictors of bleeding, transfusion practice and strategies of blood cell salvaging during liver transplantation 
World Journal of Hepatology  2013;5(1):1-15.
Blood loss during liver transplantation (OLTx) is a common consequence of pre-existing abnormalities of the hemostatic system, portal hypertension with multiple collateral vessels, portal vein thrombosis, previous abdominal surgery, splenomegaly, and poor “functional” recovery of the new liver. The intrinsic coagulopathic features of end stage cirrhosis along with surgical technical difficulties make transfusion-free liver transplantation a major challenge, and, despite the improvements in understanding of intraoperative coagulation profiles and strategies to control blood loss, the requirements for blood or blood products remains high. The impact of blood transfusion has been shown to be significant and independent of other well-known predictors of posttransplant-outcome. Negative effects on immunomodulation and an increased risk of postoperative complications and mortality have been repeatedly demonstrated. Isovolemic hemodilution, the extensive utilization of thromboelastogram and the use of autotransfusion devices are among the commonly adopted procedures to limit the amount of blood transfusion. The use of intraoperative blood salvage and autologous blood transfusion should still be considered an important method to reduce the need for allogenic blood and the associated complications. In this article we report on the common preoperative and intraoperative factors contributing to blood loss, intraoperative transfusion practices, anesthesiologic and surgical strategies to prevent blood loss, and on intraoperative blood salvaging techniques and autologous blood transfusion. Even though the advances in surgical technique and anesthetic management, as well as a better understanding of the risk factors, have resulted in a steady decrease in intraoperative bleeding, most patients still bleed extensively. Blood transfusion therapy is still a critical feature during OLTx and various studies have shown a large variability in the use of blood products among different centers and even among individual anesthesiologists within the same center. Unfortunately, despite the large number of OLTx performed each year, there is still paucity of large randomized, multicentre, and controlled studies which indicate how to prevent bleeding, the transfusion needs and thresholds, and the “evidence based” perioperative strategies to reduce the amount of transfusion.
PMCID: PMC3562721  PMID: 23383361
Transplantation surgery; Liver dysfunction; Liver transplant; Intraoperative bleeding; Intraoperative transfusion; Autotransfusion; Autologous transfusions; Transfusion requirements; Blood salvage; Cell salvage
8.  The Incidence of Portal Vein Thrombosis at Liver Transplantation 
Hepatology (Baltimore, Md.)  1992;16(5):1195-1198.
The incidence of portal vein thrombosis was examined in 885 patients who received orthotopic liver transplantations for various end-stage liver diseases between 1989 and 1990. The thrombosis was classified into four grades. Grade 1 was thrombosis of intrahepatic portal vein branches, grade 2 was thrombosis of the right or left portal branch or at the bifurcation, grade 3 was partial obstruction of the portal vein trunk, and grade 4 was complete obstruction of the portal vein trunk. Among the 849 patients without previous portosystemic shunt, 14 patients (1.6%) had grade 1, 27 patients (3.2%) had grade 2, 27 patients (3.2%) had grade 3 and 49 patients (5.8%) had grade 4 portal vein thrombosis. The incidence of portal vein thrombosis was highest (34.8%) in the patients with hepatic malignancy in the cirrhotic liver, followed by those with Budd-Chiari syndrome (22.2%) and postnecrotic cirrhosis of various causes (15.7%). The patients with encephalopathy, ascites, variceal bleeding, previous splenectomy and small liver had significantly higher incidences of portal vein thrombosis than the others. The total incidence of portal vein thrombosis among the 36 patients with previous portosystemic shunt was 38.9%, which was significantly higher than that (13.8%) of those without shunt.
PMCID: PMC2989675  PMID: 1427658
9.  Liver transplantation for “mass-forming” sclerosing cholangitis after laparoscopic cholecystectomy☆ 
Chronic biliary obstruction consequence of a bile duct injury may require liver transplantation (LT) in case of secondary biliary cirrhosis, intractable pruritus or reiterate episodes of cholangitis. “Mass-forming” sclerosing cholangitis leading to secondary portal vein thrombosis and pre-sinusoidal portal hypertension has not been reported so far.
We present the case of a patient who underwent laparoscopic cholecystectomy for Mirizzi syndrome. The persistent bile duct obstruction due to a residual gallstone fragment was treated by a prolonged biliary stenting. Following repeated bouts of cholangitis, a fibrous centrohepatic scar developed, conglobating and obstructing the main branches of the portal vein and of the biliary tree. The patient developed secondary portal vein thrombosis and portal hypertension. After an extensive diagnostic work-up, including surgical exploration to rule out malignancy, the case was successfully managed by liver transplantation.
Mass-forming sclerosis of the bile duct and biliary bifurcation may develop as a consequence of chronic biliary obstruction and prolonged stenting. Secondary portal vein thrombosis and pre-sinusoidal portal hypertension represents an unusual complication, mimicking Klatskin tumor.
A timely and proper management of post-cholecystectomy complications is of mainstay importance. Early referral to a specialized hepato-biliary center is strongly advised.
PMCID: PMC3785926  PMID: 23995476
Biliary obstruction; Biliary stent; Cholangiocarcinoma; Gallstones; Portal hypertension
10.  Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients 
AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT).
METHODS: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence.
RESULTS: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), α fetoprotein level (< 200, 200 to 2000, or > 2000; P < 0.0001), γ-GT activity (N, N to 2N or > 2N; P = 0.02), the number of nodules (1, 2-3 or ≥ 4; P = 0.02), maximal diameter of the largest nodule (< 3 cm, 3 to 5 cm or > 5 cm; P < 0.0001), the sum of the diameter of the nodules (< 3 cm, 3 to 5 cm, 5 to 10 cm or >10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06).
CONCLUSION: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation.
PMCID: PMC4087490  PMID: 17143948
Immunosuppression; Hepatocellular carcinoma; Tumor differentiation; Liver transplantation
11.  Transplantation for type 1 diabetes mellitus. Whole organ or islets? 
Hippokratia  2009;13(1):6-8.
Two types of transplants are offered to patients with complicated insulin dependent diabetes mellitus: a) whole pancreas transplantation, b) pancreatic islet transplantation. A total of 29000 whole pancreas transplantations and 1500 islet transplantations have been performed worldwide until today. Patient survival for whole pancreas recipients is 85% five years after transplantation, whereas very few islet studies focus on patient survival. Graft survival for whole pancreas recipients is 90%, 70% and 45%, at one, five and ten years after transplantation respectively. On the other hand, only 44% of islet recipients are still insulin free, one year after engraftment. If the definition of a successful islet transplantation is not insulin independence but production of C-peptide, then 80% of the same islet recipients have a functioning graft by the end of the first post-transplant year. It is a known fact that whole pancreas transplantation has significant complications. The most common complications after whole organ transplantation include technical failures, acute rejection and CMV infection, whereas islet transplantation is associated with portal vein thrombosis, bleeding, emergency exploratory laparotomy, liver steatosis and rapamune-induced mouth ulcers. The cumulative cost of a whole organ transplantation is about ?40,000. On the other hand, the cumulative cost of a pancreatic islet transplant is estimated to be higher than ?120,000. Whole organ transplantation halts the late complications of diabetes, namely vasculopathy, retinopathy, nephropathy and neuropathy. Although similar claims are made for islet transplantation, its impact on long-term diabetic complications is possible but not proven. Currently, in North America, lean young donors are utilized for whole organ transplants, whereas overweight or older donors are utilized for islet transplants. In conclusion, although islet transplantation is an extremely promising therapy and probably the way of the future, whole organ transplant is still the gold standard according to evidence-based medicine.
PMCID: PMC2633258  PMID: 19240814
pancreas; islets; transplantation; diabetes
12.  Portal Interventions in Liver Transplant Recipients 
Portal vein interventions in liver transplant recipients represent a group of interventions in the management of several disease entities including portal vein stenosis, portal vein thrombosis, and recurrent liver cirrhosis with portal hypertension with and without gastric varices. The procedures performed in these patient populations include portal vein angioplasty with or without stent placement for portal vein stenosis, portal vein thrombolysis with or without stent placement for portal vein thrombosis, transjugular intrahepatic portosystemic shunts or splenic embolization for cirrhosis, and balloon-occluded retrograde transvenous obliteration for gastric varices. This article discusses these disease entities and the minimal invasive procedures used in their management.
PMCID: PMC3444876  PMID: 23729979
transplant; liver; vascular complications; endovascular; portal; portal hypertension; TIPS; BRTO
13.  76 Factors Associated with Development of Food Allergy in Liver-Transplanted Children 
The development of food allergy (FA) after transplantation has been described mainly about liver transplantation in children (Pediatr Allergy Immunol. 2009; 20: 741–747). It has been becoming important issue in this population. Although tacrolimus immunosuppressive therapy has been considered a significant risk factor (J Allergy Clin Immunol. 2011; 127: 1296–1298), other risk factors are not identified yet. This study was undertaken to evaluate the risk factors other than tacrolimus immunosuppressive therapy.
This study was a retrospective analysis of pediatric liver transplant recipients in our hospital. We reviewed the medical records of all patients who underwent liver transplantation during study period. Data collected including preceding-hepatic diseases, the number of previous surgeries, age at liver transplantation and etc.
Between November 2005 and May 2010, 106 children received liver transplantation. The most common indication for liver transplantation was biliary atresia (BA; 47 patiens, 44.3%). The other conditions were: congenital metabolic diseases in 27 patients, fulminant hepatic failure in 19, liver cirrhosis in 6, congenital absence of portal vein in 3, congenital hepatic fibrosis in 2 and hepatic tumor in 2 patients. After transplantation, all the patients received immunosuppressive therapy based on tacrolimus regimen. Fifteen patients (10 female and 5 male) developed new-onset FA (14.2%). The average age at transplantation was 10 months and FA has been developed within 2 years (median 11 months, IQR, 4.5–19.0). Eleven patients with BA (23.4%) and 4 patients with the other conditions (6.8%) developed new-onset FA (P = 0.023). Among the patients who developed FA, the number of previous surgeries was significantly higher in patients with BA (P = 0.008).
New-onset food allergy after liver transplantation is now becoming a significant problem. We observed a trend toward an excess of FA in patients with BA compared to patients with other indications for liver transplantation. Patients with BA received surgical operations in several times before liver transplantation. Frequent operations might add some stimulation to generate new-onset FA and should be considered as a susceptible subgroup that requires specific attention.
PMCID: PMC3512931
14.  CO2 wedged hepatic venography in the evaluation of portal hypertension 
Gut  2000;46(6):856-860.
BACKGROUND/AIMS/METHODS—During hepatic vein catheterisation, in addition to measurement of hepatic venous pressure gradient (HVPG), iodine wedged retrograde portography can be easily obtained. However, it rarely allows correct visualisation of the portal vein. Recently, CO2 has been suggested to allow better angiographic demonstration of the portal vein than iodine. In this study we investigated the efficacy of CO2 compared with iodinated contrast medium for portal vein imaging and its role in the evaluation of portal hypertension in a series of 100 patients undergoing hepatic vein catheterisation, 71 of whom had liver cirrhosis.
RESULTS—In the overall series, CO2 venography was markedly superior to iodine, allowing correct visualisation of the different segments of the portal venous system. In addition, CO2, but not iodine, visualised portal-systemic collaterals in 34 patients. In cirrhosis, non-visualisation of the portal vein on CO2 venography occurred in 11 cases; four had portal vein thrombosis and five had communications between different hepatic veins. Among non-cirrhotics, lack of portal vein visualisation had a 90% sensitivity, 88% specificity, 94% negative predictive value, and 83% positive predictive value in the diagnosis of pre-sinusoidal portal hypertension.
CONCLUSIONS—Visualisation of the venous portal system by CO2 venography is markedly superior to iodine. The use of CO2 wedged portography is a useful and safe complementary procedure during hepatic vein catheterisation which may help to detect portal thrombosis. Also, lack of demonstration of the portal vein in non-cirrhotic patients strongly suggests the presence of pre-sinusoidal portal hypertension.

Keywords: portal thrombosis; liver cirrhosis; idiopathic portal hypertension; splanchnic haemodynamics
PMCID: PMC1756445  PMID: 10807900
15.  Portal vein thrombosis in a patient with HCV cirrhosis and combined hemophilia A and thrombophilia V Leiden 
The relation of hemophilia A with thrombophilia V Leiden is extremely rare in the literature. Furthermore, hemophiliac patients have an increased risk of severe life-threatening hemorrhage, blood transfusions, and therefore hepatitis transmission, mainly hepatitis C (HCV).
Aims and methods
We present a 54-year-old male with a 5-year history of decompensated liver cirrhosis on the grounds of HCV hepatitis, hemophilia A, and thrombophilia V Leiden. He was admitted to our department because of severe abdominal distension, resembling ‘tense ascites’ despite the use of diuretics. Clinical examination showed shifting dullness and a protuberant abdomen, while hematological and blood chemistry results revealed thrombopenia (platelets: 77000/mL) and hypoalbuminemia. Repeated abdominal paracentesis (under factor VIII administration) failed to remove ascitic fluid, while abdominal echosonography and computed tomography revealed severe edema of mesenterium and intraabdominal viscus and the absence of free ascitic fluid, atrophic cirrhotic liver, and splenomegaly. Moreover, abdominal doppler echosonography revealed signs of portal hypertension, previous portal vein thrombosis, and revascularization of the portal vein. Gastroscopy showed esophageal varices grade II, without signs of bleeding. A-FP and all other laboratory examinations were normal.
Our patient was intravenously treated with albumine and diuretics (furosemide) with mild improvement of his abdominal distension. During his hospitalization he presented an episode of spontaneous bacterial peritonitis and hepatic encephalopathy, which were successfully treated with lactulose clysmas and ciprofloxacine. He was discharged in a good general condition.
According to our case we consider the false clinical picture of ‘tense ascites’ of our patient as a rare clinical presentation of decompensated liver cirrhosis, with severe edema of mesenterium and viscus, on the grounds of preexisting portal vein thrombosis, in a patient with combined hemophilia A and thrombophilia V Leiden.
PMCID: PMC2988613  PMID: 21127694
portal vein thrombosis; HCV cirrhosis; hemophilia A; thrombophilia V Leiden
16.  Hepatic artery thrombosis following pediatric liver transplantation: Assessment of blood flow measurement in allografts 
Clinical transplantation  1989;3:184-189.
The purpose of this study was to define parameters which could be predictive of hepatic artery thrombosis, which continues to be a major complicating factor in pediatric liver transplantation. The hepatic blood flow of 14 pediatric liver patients (15 grafts) who weighed less than 15 kg was measured electromagnetically during orthotopic liver transplantation. The results of blood flow determination and the clinical data in 7 patients (8 grafts) who developed hepatic artery thrombosis were compared with those of 7 control patients. All patients with a hepatic arterial flow of less than 60 ml/min developed hepatic artery thrombosis (4/8 vs. 0/7; p < 0.05), and the patients with hepatic artery thrombosis exhibited higher total hepatic and portal vein flow per 100 gram of liver tissue (262 vs. 136 ml/min; p < 0.001 and 222 vs. 80 ml/min; p < 0.025, respectively) as well as longer cold preservation time (384 vs. 326 min; p < 0.025). The results of our study suggest that hepatic arterial flows of less than 60 ml/min are critical for the development of hepatic artery thrombosis, and that portal venous overflow and increased preservation times may contribute to the development of hepatic artery thrombosis.
PMCID: PMC3000218  PMID: 21151746
liver transplantation; hepatic artery thrombosis; flowmeter
17.  Surgical complications in human orthotopic liver transplantation 
Acta chirurgica Belgica  1987;87(3):193-204.
Between March 1, 1980 and December 31, 1984, 393 orthotopic liver transplantations (OLT) were performed in 313 consecutive recipients.
Technical complications were responsable for a substantial morbidity (41/393 allograft loss – 10,4%) and mortality (26/313 patient loss – 8,3%).
Failure of the biliary tract reconstruction, mainly expressed as leakage and obstruction, is the most frequent complication of OLT (52/393 grafts – 13,2%). Biliary tract complication (BTC) was directly responsible for 5 deaths (9,6%).
Reliance upon standardized methods of direct duct-to duct repair with T-tube (CC-T) and Roux-Y choledocho-jejunostomy (RYCH-J), appropriate postoperative investigation and treatment will reduce morbidity and mortality of BTC. A complicated CC-T will be conversed to a RYCH-J; a complicated RYCH-J needs surgical correction.
Hepatic artery thrombosis (HAT)has become the “Achilles heel” of OLT. HAT is expressed by three different patterns: fulminant hepatic necrosis, delayed bile leakage and relapsing bacteremia. Diagnosed in 27 grafts (6,8%), HAT was responsible for 16 deaths (16/25 pat : 64%). The only chance to rescue patients presenting HAT is an early diagnosis and prompt retransplantation before occurrence of septic complications.
Aneurysm of the hepatic arterial supply (4/393 grafts – 1%) also needs aggressive surgery because of the high rate of fatal rupture (3/4 pat – 75%).
The incidence of thrombosis of the reconstructed portal vein (PVT) was only 2,2% (7 pat.), three inferior vena caval thromboses (0,9%) (CVT) were diagnosed after OLT. Four of the 7 patients whose portal veins clotted are alive. Three have their original graft. One patient, presenting both PVT and CVT, was rescued by prompt retransplantation. PVT was responsible for 3 patient (3/7 pat – 42,8%) and 4 graft losses (4/7 pat – 57%). The rate of graft (3/3) and patient loss (2/3) was even higher after CVT.
PMCID: PMC2987662  PMID: 3303776
Liver diseases; transplantation; surgery; digestive system; postoperative complications; prognosis
18.  Establishment of a new pig model for auxiliary partial orthotopic liver transplantation 
AIM: To establish a new pig model for auxiliary partial orthotopic liver transplantation (APOLT).
METHODS: The liver of the donor was removed from its body. The left lobe of the liver was resected in vivo and the right lobe was used as a graft. After the left lateral lobe of the recipient was resected, end-to-side anastomoses of suprahepatic inferior vena cava and portal vein were performed between the donor and recipient livers, respectively. End-to-end anastomoses were made between hepatic artery of graft and splenic artery of the host. Outside drainage was placed in donor common bile duct.
RESULTS: Models of APOLT were established in 5 pigs with a success rate of 80%. Color ultrasound examination showed an increase of blood flow of graft on 5th d compared to the first day after operation. When animals were killed on the 5th d after operation, thrombosis of hepatic vein (HV) and portal vein (PV) were not found. Histopathological examination of liver samples revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobules structure disorganized in graft. Infiltration of inflammatory cells was mild in portal or central vein area. Hematologic laboratory values and blood chemical findings revealed that compared with group A (before transplantation), mean arterial pressure (MAP), central venous pressure (CVP), buffer base (BB), standard bicarbonate (SB) and K+ in group B (after portal vein was clamped) decreased (P<0.01). After reperfusion of the graft, MAP, CVP and K+ restored gradually.
CONCLUSION: Significant decrease of congestion in portal vein and shortened blocking time were obtained because of the application of in vitro veno-venous bypass during complete vascular clamping. This new procedure, with such advantages as simple vessel processing, quality anastomosis, less postoperative hemorrhage and higher success rate, effectively prevents ischemia reperfusion injury of the host liver and deserves to be spread.
PMCID: PMC4250610  PMID: 15682494
Auxiliary partial orthotopic liver transplantation; Model pig
19.  Portal Vein Thrombosis and Liver Transplant Survival Benefit 
Portal vein thrombosis (PVT) complicates the liver transplant operation and potentially affects waiting list survival. The implications on calculations of survival benefit, which balance both waiting list and posttransplant survival effects of PVT, have not been determined. The objective of this study is to describe the effect of PVT on the survival benefit of liver transplantation.
Using Scientific Registry of Transplant Recipients (SRTR) data on adult liver transplant candidates wait-listed between September 2001 and December 2007, Cox proportional hazards models were fitted to estimate the covariate-adjusted effect of PVT on transplant rate, waiting list survival and posttransplant survival. We then used sequential stratification to estimate liver transplant survival benefit by cross-classifications defined by MELD score and PVT status.
The prevalence of reported PVT among 22,291 liver transplant recipients was 4.02% (N = 897). PVT was not a predictor of waiting list mortality (HR=0.90; p=0.23), but was a predictor of posttransplant mortality (HR=1.32; p=0.02). Overall, transplant benefit was not significantly different for patients with PVT vs. without PVT (p=0.21), but there was a shift in the benefit curve. Specifically, the threshold for transplant benefit among patients without PVT was MELD > 11, compared to MELD > 13 for PVT patients.
PVT is associated with significantly higher posttransplant mortality, but does not affect waiting list mortality. Among low-MELD patients, PVT is associated with less transplant survival benefit. Clinicians should carefully consider the risks of liver transplantation in clinically stable patients who have PVT.
PMCID: PMC2915450  PMID: 20677291
mesenteric thrombosis; liver transplant survival; waiting list mortality; posttransplant survival; MELD score
Transplantation  1990;50(4):564-567.
Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4°C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37°C) (n=8) or hypothermic (32°C) (n=8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37°C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P<0.05), and there was lower bile output (P<0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P<0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P<0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.
PMCID: PMC2967246  PMID: 2219274
21.  Portal hypertension due to portal venous thrombosis: Etiology, clinical outcomes 
The thrombophilia in adult life has major implications in the hepatic vessels. The resulting portal vein thrombosis has various outcomes and complications. Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver failure needing liver transplantation are known well. The newly formed collateral venous circulation showing itself as pseudocholangicarcinoma sign and its possible clinical reflection as cholestasis are also known from a long time. The management strategies for these complications of portal vein thrombosis are not different from their counterpart which is cirrhotic portal hypertension, but the prognosis is unquestionably better in former cases. In this review we present and discuss the portal vein thrombosis, etiology and the resulting clinical pictures. There are controversial issues in nomenclature, management (including anticoagulation problems), follow up strategies and liver transplantation. In the light of the current knowledge, we discuss some controversial issues in literature and present our experience and our proposals about this group of patients.
PMCID: PMC4146813  PMID: 17552000
Portal vein thrombosis; Pseudocholangiocarcinoma sign; Thrombophilia
22.  Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial 
BMC Surgery  2013;13:22.
In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver transplantation is currently managed by transfusion of red blood cell concentrates, platelet concentrates, fresh frozen plasma, and fibrinogen concentrate. Transfusion of these products may paradoxically result in an increased bleeding tendency due to aggravated portal hypertension. The hemostatic effect of these products may therefore be overshadowed by bleeding complications due to volume overload.
In contrast to these transfusion products, prothrombin complex concentrate is a low-volume highly purified concentrate, containing the four vitamin K dependent coagulation factors. Previous studies have suggested that administration of prothrombin complex concentrate is an effective method to normalize a prolonged prothrombin time in patients with liver cirrhosis. We aim to investigate whether the pre-operative administration of prothrombin complex concentrate in patients undergoing liver transplantation for end-stage liver cirrhosis, is a safe and effective method to reduce perioperative blood loss and transfusion requirements.
This is a double blind, multicenter, placebo-controlled randomized trial.
Cirrhotic patients with a prolonged INR (≥1.5) undergoing liver transplantation will be randomized between placebo or prothrombin complex concentrate administration prior to surgery. Demographic, surgical and transfusion data will be recorded. The primary outcome of this study is RBC transfusion requirements.
Patients with advanced cirrhosis have reduced plasma levels of both pro- and anticoagulant coagulation proteins. Prothrombin complex concentrate is a low-volume plasma product that contains both procoagulant and anticoagulant proteins and transfusion will not affect the volume status prior to the surgical procedure. We hypothesize that administration of prothrombin complex concentrate will result in a reduction of perioperative blood loss and transfusion requirements. Theoretically, the administration of prothrombin complex concentrate may be associated with a higher risk of thromboembolic complications. Therefore, thromboembolic complications are an important secondary endpoint and the occurrence of this type of complication will be closely monitored during the study.
Trial registration
The trial is registered at with number NTR3174. This registry is accepted by the ICMJE.
PMCID: PMC3701501  PMID: 23815798
Orthotopic Liver Transplantation; Prothrombin Complex Concentrate; Haemostatis; Bleeding; Blood Loss; Transfusion Requirements; Cirrhosis
23.  Management of Portal Vein Thrombosis in Cirrhotic Patients 
Portal vein thrombosis (PVT) not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management. The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.
PMCID: PMC3033127  PMID: 21415954
24.  Donor Safety in Live-Related Liver Transplantation 
The Indian Journal of Surgery  2011;74(1):118-126.
Living donor liver transplantation (LDLT), since its advent in late 1980’s and early 1990’s, has rapidly increased especially in countries like Japan, Korea and India where cadaveric programmes are not as well established as in the western world. The main advantage of LDLT is the availability of an organ in the elective setting in the course of a progressive liver disease. This is most applicable in patients with Cirrhosis and Hepatocellular carcinoma. LDLT, from the donor’s perspective does carry a risk of not only morbidity but mortality. To date the surgical mortality risk is estimated at 0.1% for left lateral donation and 0.5% for right liver donation. Donor mortality has been reported from various centres in India. There are reports of complications like Hepatic artery thrombosis, portal vein thrombosis and especially biliary leaks and strictures occurring at a significantly increased frequency after living as compared to deceased donor liver transplantation. The key to reduce donor morbidity and mortality is meticulous donor selection and thorough donor work up. In the present study we will analyse the factors that contributed to donor mortality and morbidity and prepare a detailed work up plan, intraoperative and post-operative strategy to reduce donor morbidity and mortality.
PMCID: PMC3259172  PMID: 23372315
Live-related liver transplant; Donor safety; Donor mortality; Donor morbidity
25.  Cavernous Transformation of Portal Vein Secondary to Portal Vein Thrombosis: A Case Report 
There are few reported cases of cavernous transformation of the portal vein (CTPV) in adults. We present a case of a 58 year-old male who was found to have this complication due to portal vein thrombosis (PVT). A 58-year old African American male with chronic alcohol and tobacco use presented with a 25-day history of weakness, generalized malaise, nausea and vomiting associated with progressively worsening anorexia and weight loss. The patient was admitted for severe anemia in conjunction with abnormal liver function tests and electrolyte abnormalities, and to rule out end stage liver disease or hepatic malignancy. The work-up for anemia showed no significant colon abnormalities, cholecystitis, liver cirrhosis, or liver abnormalities but could not rule out malignancy. An esophageogastroduodenoscopy (EGD) was suspicious for a mass compressing the stomach and small bowel. After further work-up, the hepatic mass has been diagnosed as a cavernous transformation of the portal vein (CTPV), a very rare complication of portal vein thrombosis (PVT). Cavernous Transformation of the Portal Vein (CTPV) is a rare and incurable complication of portal vein thrombosis (PVT) that should be considered as one of the differential diagnoses of a hepatic mass.
Cavernous transformation of the portal vein; Portal vein thrombosis; Portal hypertension; Hyperbilirubinemia; Hepatic mass
PMCID: PMC3279509  PMID: 22383935

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