Utility of Oral Anticoagulants as Prophylaxis of Recurrent Portal Thrombosis after Liver Transplantation.

INTRODUCTION: Portal vein thrombosis (PVT) is a relatively common finding in patients undergoing liver transplantation. Although the recommendation to prevent its recurrence is anticoagulation for a duration of 3 to 6 months, this is controversial. AIM: The aim of our study was to determine the efficacy of oral anticoagulants (OAC) as prophylaxis for recurrent PVT after liver transplantation. MATERIALS AND METHODS: Our study included 215 liver transplant patients who underwent surgery in our center from January 2012 to August 2017. We selected all patients diagnosed with PVT either pre-transplantation (using Doppler echography or Angio-CT) or during transplant surgery. All patients with PVT were initially anticoagulated with low-molecular-weight heparin in the postoperative period; at discharge they received OAC for a duration of six months. Control Doppler ultrasound was performed at 3, 6, and 12 months post-transplantation. RESULTS: PVT was identified in 37 out of 215 patients (17.2%). PVT was diagnosed with a pre-transplant vascular study in 17 out of 37 cases (45.9%). All patients were anticoagulated with OAC (warfarin) for at least 6 months. There were no cases of recurrent thrombosis and no complications associated with anticoagulant treatment throughout the follow-up period. CONCLUSIONS: The prevalence of portal thrombosis in liver transplant patients in our study was fairly high, at 17.2%. PVT was identified in nearly 50% of patients using high-quality vascular studies prior to transplant surgery. Anticoagulation with OAC for 6 months was effective in preventing a recurrence of thrombosis and there were no associated complications.

Efficacy of Direct-acting Antivirals to Improve Clinical Condition, Fibrosis, and Liver Function in Liver Transplant Recipients Infected by Hepatitis C.

BACKGROUND: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C, including transplant recipients with an advanced fibrosis stage. Our aim in this study was to assess the clinical and functional benefits and improvement in liver fibrosis after treatment with DAAs in liver transplant recipients with chronic hepatitis C virus who achieved sustained virologic response (SVR). METHODS: We retrospectively analyzed 42 patients who underwent liver transplantation (LT) at our institution and were treated with DAAs from June 2014 to December 2015. Two patients died, so we ultimately included 40 transplant patients with chronic hepatitis C who received DAAs and achieved SVR. We assessed liver function, fibrosis stage, and clinical features at the start of the treatment, and then at 6 and 12 months after SVR. The indication for LT was hepatocellular carcinoma in 8 patients (20%) and Child-Pugh score B/C in 32 patients (80%). RESULTS: The DAAs regimens were sofosbuvir plus daclatasvir (45.0%), simeprevir plus sofosbuvir (42.5%), sofosbuvir plus ledipasvir (7.5%), and ombitasvir/paritaprevir/ritonavir (5%). The mean Modified End-stage Liver Disease (MELD) score pretreatment was 10.78, and was 8.46 at 1 year after treatment (P < .05). In addition, fibrosis stage decreased significantly from 14.81 kPa to 9.07 kPa (FibroScan) at 12 months after SVR. Clinically, there was a significant improvement, including control of ascites and chronic hepatic encephalopathy. CONCLUSION: DAAs were used successfully in the treatment of hepatitis C after orthotopic liver transplantation and resulted in significant improvement in liver function as measured by MELD score, fibrosis level, and cirrhotic clinical condition, even in patients with very advanced disease.

Metabolic Syndrome After Liver Transplantation: Five-Year Prevalence and Risk Factors.

Survival after orthotopic liver transplantation (OLT) has increased over the last decades, focusing on the metabolic complications that contribute to patient morbidity and mortality. The aim of our study was to describe the prevalence of metabolic syndrome (MS), its components, and its associated factors in patients who underwent OLT in a hospital in Spain. From November 2001 to January 2014, we performed 415 transplantations in 386 patients. We analyzed 204 patients with a minimum follow-up of 1 year (77.6% were male and the mean age was 54.2+/-9.5 years). The most frequent etiology was alcohol (41%), followed by hepatitis C virus (29.1%). The indication was decompensated cirrhosis in 51.8% and hepatocellular carcinoma in 34%. According to modified National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATP III) criteria, 5 years post-transplantation MS was diagnosed in 38.2% of patients. Significant independent predictors of post-transplantation MS on logistic regression analysis were as follows: pretransplantation obesity (odds ratio [OR], 3.09; P = .056), 1-year post-transplantation obesity (OR, 3.95; P = .009), pretransplantation diabetes (OR, 4.63; P = .001), 1-year post-transplantation diabetes (OR, 3.01; P = .015), 1-year post-transplantation hypertension (OR, 1.85; P = .176), and hypertriglyceridemia at the first year after transplantation (OR, 2.32; P = .063). In our center the prevalence of MS at 5 years after OLT is slightly lower than published. The most important risk factors were obesity and diabetes (both pretransplantation and the first year post-transplantation).

Severe anemia, gastric ulcer, pneumonitis and cholangitis in a liver transplant patient: multiple organic dysfunction and one etiology: a case report.

Cytomegalovirus (CMV) is the most common viral pathogen that negatively affects the outcome of liver transplantation. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases it invades tissues, including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survivals. We carried out a study on a Spanish adult liver transplant recipient who rapidly presented anemia and was diagnosed as having Coomb negative (nonimmune) hemolytic anemia, gastric ulcer, pneumonitis, and cholangitis associated with a CMV infection.

Cutaneous mucormycosis infection by Absidia in two consecutive liver transplant patients.

Mucormycosis, although an infrequent fungal infection, has a high mortality in patients undergoing orthotopic liver transplantation. We present two cases of cutaneous Absidia mucormycosis in two successive patients undergoing liver transplantation in our hospital. In our literature search, we encountered only one published case of Absidia infection in liver transplantation.

Early and extended therapy for recurrent hepatitis C after liver transplantation.

BACKGROUND: End-stage cirrhosis due to hepatitis C virus (HCV) is one of the most common indications for orthotopic liver transplantation (OLT). Recurrence is universal and more aggressive than before OLT. The aim of this study was to evaluate the efficacy and tolerability of antiviral therapy in recurrent HCV after OLT. Therapy was started even with mild fibrosis (F < 2) and extended until 72 weeks, if it was possible. METHODS: Between November 2001 and December 2010, 279 OLTs were performed in 262 patients in our hospital; 81 (31%) for HCV-related cirrhosis. Nineteen patients were excluded because they died in the first 6 months. We treated 28 of 62 HVC patients. RESULTS: Twenty-eight patients met the indication for antiviral therapy: 21 male (75%) and 7 female (25%), with a mean age of 56 years (range, 40 to 68 years). All the patients had histologically proven recurrence liver disease: F1, 19 patients (68%); F2, 4 patients (14%), and F3, 45 patients (18%). The mean time to recurrence was 23 months, with a range of 3 to 90 months. Adverse effects (leukopenia in 82% and anemia in 79%) were treated with granulocyte colony-stimulating factor (GCSF) and erythropoietin (EPO), and dose reduction. Four patients (14%) were withdrawn from the treatment because of adverse effects. Nineteen patients achieved early virologic response (68%), and the sustained virologic response was 54% (15 of 28 patients). Five patients died (18%). CONCLUSION: Improving sustained virologic response in HCV liver transplant patients is a key goal. Antiviral therapy is safe and effective treating HCV recurrence after OLT. Starting this therapy in an early stage of hepatitis C recurrence, extending antiviral therapy (72 weeks), and avoiding dose reduction of antiviral drugs could help to achieve higher rates of sustained virological response.

Indications and effectiveness of the mammalian target of rapamycin in liver transplantation.

BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitors are new immunosuppressive drugs for organ transplantation. They are interesting for liver transplantation because of their absence of nephrotoxicity and potential antitumor effects, because calcineurin inhibitors (CNI) are associated with renal dysfunction post-CNI and tumors. We sought to analyze the indications, safety, and efficacy of mTOR among liver transplant patients at our center. METHODS: We retrospectively identified patients who were treated with mTOR for their indications for liver transplantation, type of immunosuppressive therapy, acute rejection episodes, and evolution of kidney function. RESULTS: We identified 43 (19.02%) patients treated with mTOR including 35 (81.4%) males and 8 (18.6%) females of overall average age of 56.7 (range, 44-68). In 30% of patients, the drug was introduced for kidney failure, and in 23% for actual or a high risk of hepatocellular carcinoma (HCC) recurrence. The average time to introduction of the mTOR was 6.4 months (range, 1-46). The final immunosuppressive regimen was mTOR alone (73%), or mTOR plus CNI (23%), or mTOR plus mycophenolate mofetil (4%). The average values of creatinine and urea were lower after conversion to mTOR (P < .05) with a 6.9% incidence of acute rejection episodes. CONCLUSION: The mTOR immunosuppressive drugs are safe for liver transplant patients, effectively controlling renal dysfunction. They can be used in other indications, such as neurotoxicity, de novo tumors, and high risk of HCC recurrence. More studies are needed to clarify their long-term effectiveness.

Incidence, management, and results of vascular complications after liver transplantation.

INTRODUCTION: Vascular complications show an 8%-15% incidence after liver transplantation and represent an important cause of mortality. An aggressive policy is necessary for an early diagnosis and treatment. PATIENTS AND METHODS: From 2001 to 2009, we performed 240 liver transplantations in 232 patients. We employed Doppler ultrasonography on days 1 and 4 as well as before hospital discharge and always try a radiological approach. RESULTS: The incidence of vascular complications was 7.2% (n = 18) including arterial (n = 12, 4.8%) of early thrombosis (n = 4), late thrombosis (n = 4), and stenosis (n = 4) or portal (n = 3; 1.2%) of thrombosis (n = 2) or stenosis (n = 1); or caval complications (n = 3, 1.2%). Radiologic therapy was effective in 1 patient with arterial stenosis, in the 3 patients with portal complications, and in 2 patients with caval complications. All patients with early thrombosis and 2/4 with late thrombosis required retransplantation. Surgical treatment was effective in 1 patient with late thrombosis, 3 with stenosis, and 2 with caval complications. The overall mortality rate was 16.6%; 2 patients with arterial complications and 1 with a caval complications. CONCLUSION: Vascular complications, mainly artery complications, represent serious problem after liver transplantation, which often requires retransplantation. With an aggressive policy of diagnosis and treatment, we can decrease the mortality rate from these adverse events.

Covered metal stents for the treatment of biliary complications after orthotopic liver transplantation.

BACKGROUND: Biliary complications, a major source of morbidity after orthotopic liver transplantation (OLT), are increasingly being treated by endoscopic retrograde cholangiopancreatography (ERCP). Endoscopic management has been shown to be superior to percutaneous therapy and surgery. Covered self-expandable metal stents (CSEMSs) may be an alternative to the current endoscopic standard treatment with periodic plastic stent replacement. OBJECTIVE: To assess the safety and efficacy of temporary CSEMS insertion for biliary complications after OLT. METHODS: From November 2001 to December 2009, the 242 OLT performed in 226 patients included 67 cases that developed post-OLT leaks or strictures (29.6%), excluding ischemic biliary complications. CSEMSs were used in 22 patients (33%), 18 male and 4 female, with an overall median age of 55 years (range, 29-69). In-house OLT patients underwent an index ERCP at 26 days (range, 8-784) after OLT. Their records were reviewed to determine ERCP findings, technical success, and clinical outcomes. RESULTS: ERCP with sphincterotomy was performed in all 22 patients, revealing 18 with biliary strictures alone (82%), 3 with strictures and leaks (14%), and 1 with strictures and choledocholithiasis (4%). All strictures were anastomotic. All patients had 1-2 plastic stents inserted across the anastomosis (11 had prior balloon dilation); stones were successfully removed, for an initial technical success rate of 100% (22/22). CSEMSs, were placed at the second ERCP in 14 patients, at the third in 7, and at the fourth in 1. With a median follow-up of 12.5 months (range, 3-25) after CSEMS removal, 21/22 patients (95.5%) remain stricture free and one relapsed, requiring repeat CSEMS insertion. Four patients experienced pain after CSEMS insertion. At CSEMS removal, migration was noted in 5 cases, into either the distal duodenum (n=4) or the proximal biliary tree (n=1), and embedding was seen in 1 case. There were no serious complications; no patients needed hepatojejunostomy. CONCLUSIONS: ERCP is a safe first-line approach for post-OLT biliary complications. It was highly successful in a population with anastomotic leaks and strictures. The therapeutic role of ERCP to manage biliary complications after OLT in the long term is not well known. In our experience, the high rate (close to 95%) of efficacy and its relative safety allowed us to use CSEMS to manage refractory biliary post-OLT strictures. CSEMS insertion may preclude most post-OLT hepatojejunostomies.

Risk of development of the metabolic syndrome after orthotopic liver transplantation.

Longer survival for orthotopic liver transplantation (OLT) patients over the last decade has focused emphasis on the metabolic complications that contribute to patient morbidity and mortality. The aim of our study was to analyze the prevalence of the metabolic syndrome (MS) and other risk factors after OLT among our patients at 1 year follow-up. From 2001 to 2008, we performed OLT in 210 patients with 62 exclusions leaving 148 patients for the study. We recorded age, gender, liver disease, smoking status, pre- and post-OLT body mass index, pre- and post-OLT arterial blood pressure, pre- and post-OLT fasting blood glucose, pre- and post-OLT high-density lipoproteins and triglycerides, family history of diabetes, hepatitis B and C virus status, immunosuppressive therapy, and corticosteroid bolus for rejection episodes. The MS was defined according to modified ATP III criteria. At month 12 after OLT, 29/148 patients (19.6%) developed the MS. The associated factors were obesity and hyperlipidemia pre-OLT, familial and personal history of diabetes as well as alcoholic cirrhosis. By multivariate analysis, pre-OLT body mass index (odds ratio, 3.7 [1.3-10.5]) and pre-OLT diabetes (odds ratio, 2.9 [1.1-7.9]) were independent risk factors.

Milan criteria versus San Francisco criteria in hepatocellular carcinoma: our center's experience.

BACKGROUND AND AIM: Liver transplantation (OLT) represents the best treatment for hepatocellular carcinoma (HCC) in advanced cirrhosis showing a 70% 5-year survival rate. Our study sought to compare overall survivals among patients who underwent OLT under Milan Criteria (MC) or San Francisco Criteria (UCSFC). METHODS: We retrospectively analyzed patients who underwent liver transplantation for HCC in our institution from November 2001 to December 2007. We analyzed age, gender, OLT indication, maximal tumor size, histology, and survival. We compared survival among patients who met MC versus UCSFC. RESULTS: From November 2001 to December 2007, 48/177 (27%) liver transplantations performed in our hospital were indicated due to HCC. The two patients who did not show any tumor in the explanted liver (false-positive ratio 4.2%) were excluded from the analysis. Another two patients were included who showed incidental HCC lesions (false-negative ratio 1.7%), yielding 48 analyzed patients. The mean diameter of the HCC nodules were 3.1 cm before OLT and 3.8 cm in the pathologic examination, a statistically significant difference. Two patients exceeded MC before OLT, and six patients showed this feature in the explanted liver. There was a significant difference in the degree of vascular invasion between the two groups. Overall mortality was 25.9% at 4 years; the MC group show an 11.9% versus UCSFC group, a 66.6% rate. CONCLUSIONS: HCC is a common indication for OLT. Hepatitis C virus is the most common etiology. Survival among the MC group was significantly better than that of subjects beyond the MC, a difference that supports the use of MC for HCC.

FibroScan evaluation of liver fibrosis in liver transplantation.

INTRODUCTION: Liver biopsy remains the gold standard to evaluate fibrosis. However, it is invasive and uncomfortable as well as associated with complications. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness in kilopascals. Body mass index (BMI) greater than 28 is associated with high rates of invalid tests. Liver transplant patients show increased rates of obesity. We do not yet have many data about the usefulness of FibroScan in liver transplantation. AIMS: To analyze the applicability of FibroScan to assess fibrosis in liver transplantation and study the association between obesity and valid tests. MATERIAL AND METHODS: We prospectively assessed the performance of transient elastography in 29 liver transplant patients from February to May 2008. We prospectively studied the success rate, the elasticity (stiffness) in kilopascals, and the BMI. RESULTS: The BMI was greater than 30 kg/m(2) in four patients; 25 to 30 kg/m(2) in eight; and 17 had BMI < 25 kg/m(2). The overall success of FibroScan was 24/29 (82.7%). However, among patients with BMI > 30 kg/m(2), it was 2/4 (50%), whereas for BMI <25 kg/m(2) it climbed to 100%. The average duration of the procedure was 211.52 seconds for BMI <25 kg/m(2); 236 seconds for BMI between 25 and 30 kg/m(2); and 361 seconds in patients with a BMI > 30 kg/m(2)-differences that were statistically significant. CONCLUSIONS: FibroScan seemed to be a promising approach to assess liver fibrosis.BMI is a limiting factor toward achieving a valid test; FibroScan had limited usefulness in obese patients.

Interleucina-18 (IL-18) y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda / No disponible

Objetivo: se trata de comparar prospectivamente el comportamientodurante la primera semana del ingreso de los niveles de interleucina-18 (IL-18), y otros parámetros inmunológicos entre pacientescon pancreatitis aguda con y sin criterios de gravedad, así comoentre pacientes con y sin desarrollo ulterior de seudoquiste.Pacientes y métodos: se compararon en 36 pacientes conpancreatitis aguda los resultados de sTNF-RI, IL-1Ra, IL-6 e IL-18los días 1, 2, 3 y 7 desde el ingreso entre pancretitis leve, grave y ungrupo control (13 pacientes) con cólico biliar simple, así como entrepacientes con o sin seudoquiste.Resultados: al comparar pancreatitis leve con grave, IL-18 fuesignificativamente superior sólo el primer día en las pancreatitis gravesy los otros parámetros a partir del segundo día de forma mantenida.También en pacientes que desarrollaron seudoquiste, IL-18 estuvosignificativamente elevada el primer día.Conclusiones: IL-18 resultó el marcador más precoz de complicacionesy gravedad de la pancreatitis aguda a nivel sistémico y local(seudoquiste)

Objective: our aim was to prospectively compare the behaviorof interleukin 18 (IL-18) levels and other immunological parametersduring the first week of hospitalization between acute pancreatitispatients with and without severity criteria, as well asbetween patients with and without late pseudocyst development.Patients and methods: in 36 patients with acute pancreatitiswe compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days1, 2, 3 and 7 after hospitalization between mild pancreatitis, severepancreatitis, and a “control” group (13 patients) with uncomplicatedbiliary colic, as well as between patients with and withoutpseudocyst.Results: on comparing mild to severe pancreatitis, IL-18 wassignificantly higher only the first day in severe pancreatitis, whilethe other parameters were steadily higher after the second day. Inpatients developing pseudocyst, IL-18 was also noticeably higherthe first day.Conclusions: IL-18 appears to be the earliest marker of complicationsand severity in acute pancreatitis at both the systemicand local level (pseudocyst)

Colitis ulcerosa, tacrolimus y curación mucosa / No disponible

No disponible

[Interleukin 18 (IL-18) and other immunological parameters as markers of severity in acute pancreatitis]. / Interleucina-18 (IL-18) y otros parámetros inmunológicos como marcadores de gravedad en la pancreatitis aguda.

OBJECTIVE: Our aim was to prospectively compare the behavior of interleukin 18 (IL-18) levels and other immunological parameters during the first week of hospitalization between acute pancreatitis patients with and without severity criteria, as well as between patients with and without late pseudocyst development. PATIENTS AND METHODS: In 36 patients with acute pancreatis we compared sTNF-RI, IL-1Ra, IL-6, and IL-18 levels at days 1, 2, 3 and 7 after hospitalization between mild pancreatitis, severe pancreatitis, and a "control" group (13 patients) with uncomplicated biliary colic, as well as between patients with and without pseudocyst. RESULTS: On comparing mild to severe pancreatitis, IL-18 was significantly higher only the first day in severe pancreatitis, while the other parameters were steadily higher after the second day. In patients developing pseudocyst, IL-18 was also noticeably higher the first day. CONCLUSIONS: IL-18 appears to be the earliest marker of complications and severity in acute pancreatitis at both the systemic and local level (pseudocyst).

[The prophylaxis against post-liver-transplant hepatitis B re-infection]. / Profilaxis de reinfección por el virus de la hepatitis B postrasplante hepático.

OBJECTIVE: To review the prophylaxis against post-liver transplantation hepatitis B reinfection with anti-hepatitis B immunoglobulin and nucleoside analogues. METHOD: A bibliographic search was carried out using Pubmed, entering the following key words: hepatitis B and liver transplantation and (hepatitis B hyperimmune globulin and lamivudine and adefovir dipivoxil) up to June 2006. The initial search was filtered using the terms clinical trial, randomized clinical trial and review. The data contained in selected studies were reviewed. RESULTS: A total of 53 works were found. Prophylaxis with anti-HB immunoglobulin and lamivudine is the best strategy for avoiding recurrence of the hepatitis B virus in patients undergoing hepatic transplants; achieving very low reinfection rates (0-10%) with follow up periods of between 1-5 years. There is a great degree of variability (dose, duration and method of HBIg administration) in the prophylactic protocols reviewed. The use of low doses of anti-HB immunoglobulin (administered intravenously followed by intramuscular administration, or administered intramuscularly from the anhepatic stage), and lamivudine in patients who receive transplants with a low risk of recurrence, shows prophylactic efficacy comparable to the use of high doses of anti-HB immunoglobulin. Furthermore, it implies a considerable reduction in costs. CONCLUSIONS: The availability of suitably designed clinical trials is required to design a more cost-effective protocol and reduce variability.