G.R. Coelho

Orthotopic Liver Transplantation for Hepatocellular Carcinoma: One Center's Experience in the Northeast of Brazil

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. In this study, we sought to assess the outcome of patients with HCC who underwent orthotopic liver transplantation (OLT) in a center in the northeast of Brazil. Between May 2002 and July 2008, 294 OLTs were performed at our center. In 45 patients, HCC was confirmed by histological examination of the explant. Patients were predominantly men of ages ranging from 14-67 years. Hepatitis C virus was involved in 55.4% of the cases. Alpha fetoprotein (AFP) levels were normal in 65.2% of the patients and surpassed 100 ng/mL in only 10.4%. The median waiting time on the list was 10 months. Seventeen patients (37.7%) presented a solitary nodule, 19 (42.2%) had 2 or 3 nodules, and 9 patients (20%) had more than 3 nodules. The maximal diameter of the largest tumor was <3 cm in 26 patients (57.7%) and exceeded 5 cm in 6 patients (13.3%). Ten tumors were well differentiated, 32 were moderately differentiated, and 3 were poorly differentiated. Eleven tumors showed microvascular invasion. There have been 4 tumor recurrences. There was an association between microvascular invasion and tumor recurrence with a statistically significant relative risk. In conclusion, OLT is an excellent option for patients with HCC. The recurrence rate was low (<10%). However, we believe that more prospective studies are needed about OLT beyond the Milan criteria because our study suggested that microvascular invasion may be more important than tumor size or number.

Synchronous hepatocellular carcinoma and renal cell carcinoma in a liver transplant recipient: a case report.

A 52-year-old male with liver cirrhosis secondary to hepatitis virus C, Child-Pugh score of C10, and Model for End-stage Liver Disease score of 20 was listed for liver transplant. During the pretransplant management, an abdominal computed tomography (CT) and magnetic resonance imaging (MRI, Fig. 1) showed a 2.7 2.2 cm mass in the liver and a 1.7 1.2 cm tumor in the right kidney. The liver mass on the CT was hyperdense with the liver parenchyma in the early arterial phase of contrast enhancement and hypodense in the portal phase; on the MRI, on T1-weighted sequences, it was hypointense to the liver and, on T2weighted, it was hyperintense, suggesting hepatocellular carcinoma (HCC). The renal tumor on the CT and was a solitary solid lesion with contrast enhancement during the arterial phase; on the MRI, on T2-weighted images, it was hyperintense to the liver; on T1-weighted, it was hypointense, with a high degree of confidence in diagnosing renal cell carcinoma (RCC). Being a Child-Pugh C patient, he had a prohibitive risk to perform either a biopsy of the kidney tumor or its resection. Based on the fact that renal metastasis from a primary hepatocellular carcinoma is a extremely rare event (1), on the initial stage of both tumors and finally on the MRI and CT findings, we considered the possibility of two synchronous tumors and decided not to contraindicate the liver transplant. During the liver transplantation procedure, after the recipient’s hepatectomy, we performed a partial nephrectomy to resect the kidney mass. Then, the donor liver was implanted. Histopathological analysis confirmed a synchronous HCC and RCC. He showed a good recovery and left the hospital 7 days after the transplant. His immunosuppression regimen was based on tacrolimus and prednisone. After a 12-month followup, patient is alive with good graft function and has no clinical or CT sign of any other tumor. Synchronous early primary cancers are rare. One study showed an incidence of 3.7% of synchronous cancers related to RCC. The most common sites involved were prostate, bladder, and lung. The occurrence of synchronous RCC and HCC is extremely rare (2). There is just one case of synchronous HCC and RCC resected simultaneously during a liver transplantation procedure, recently published on the literature (3). The prognosis of RCC is not likely to be changed by immunosuppression. However, a 5-year follow-up is necessary to confirm the results. The possibility of a synchronous tumor should be considered in cirrhotic patients with HCC. Jose Huygens Parente Garcia Gustavo Rego Coelho Fernanda Paula Cavalcante Jose Telmo Valenca Junior Ivelise Regina Canito Brasil Gleydson Cesar-Borges Paulo Everton Garcia Costa Cyntia Ferreira Gomes Viana Tarciso Daniel Santos Rocha Joao Batista Marinho Vasconcelos Centro de Transplante de Figado do Ceara Hospital Universitario Walter Cantidio Fortaleza, Brazil

Single-Center Transfusion Rate for 555 Consecutive Liver Transplantations: Impact of Two Eras

Orthotopic liver transplantation (OLT) is the treatment of choice for patients with acute or chronic end-stage liver disease, irresectable primary liver tumor, and metabolic disorders. Historically, OLT has been associated with considerable blood loss and the need for transfusions. However, over the years there has been reduction is need for blood products. The aim of this article was to compare two distinct eras for perioperative blood transfusion rate among patients undergoing OLT; Era I, 200 transplantations in 188 patients, and Era II, 355 transplantations in 339 patients. The donor mean age was 33.70 (Era I) versus 35.34 (Era II). Cause of death in both eras was traumatic brain injury followed by cerebral vascular accident. Organ recipient data showed a mean age of 48.87 (Era I) versus 46.49 (Era II). During Era I patients with Child B (56.8%) prevailed, followed by Child C (35.4%) and Child A (7.8%). In Era II also patients with Child B (53.1%) prevailed, followed by Child C (39.6%) and Child A (7.3%). The prevalence of hepatocellular carcinoma (HCC) during Era I was 9% (18) and in Era II 20% (71). The use of blood products in the perioperative period: was as follows packed red blood cells 1.76 (Era I) versus 0.57 (Era II) units; fresh frozen plasma 1.89 (Era I) versus 0.49 (Era II) units; platelets 2.16 (Era I) versus 0.28 (Era II) units; and cryoprecipitate 0.08 (Era I) versus 0.03 (Era II) units. OLT using the piggyback technique was performed with a transfusion rate below <30%, and it reduced blood loss and prevented severe hemodynamic instability.

Combined liver-kidney transplantation: experience at a brazilian university hospital

Background Combined liver-kidney transplant is a routine procedure in many transplant centers. The increase in its number coincided with the introduction in 2002 of the MELD (Model for End-stage Liver Disease) score for allocation of livers, prioritizing patients with renal dysfunction. Aim To analyze the experience with combined liver-kidney transplantation in a liver transplant center in Brazil. Method A retrospective review was conducted. All transplants were performed using grafts from deceased donors. Results Sixteen combined liver-kidney transplantations were performed in the same period, which corresponds to 2.7% and 2.5% of the kidney and liver transplants, respectively. Fourteen patients were male (87.5 %) and two were female (12.5%). The average patients and donors age was 57.3±9.1 and 32.7±13.1, respectively. The MELD score mean was 23.6±3.67. The main cause of liver dysfunction were chronic hepatitis C virus (n=9). As for renal dysfunction, diabetic nephropathy (n=4) was the most frequent. There were six deaths, two of them by severe dysfunction of the liver graft and four by infectious causes. The 1, 3 and 5 years survival rate in patients undergoing liver-kidney transplantations was 68.8%, 57.3% and 57.3%, respectively. Conclusion The survival rates achieved in this series are considered satisfactory and show that this procedure has an acceptable morbidity and survival.

LIVER TRANSPLANTATION IN JEHOVAH'S WITNESSES PATIENTS IN A CENTER OF NORTHEASTERN BRAZIL

CONTEXT Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease and acute liver failure. Currently, Brazil has a well-established public organ transplant program, performing 7,425 solid organs transplants in 2012 alone, among which 1,595 were liver transplants. Jehovahs Witnesses report 7,6 million members worldwide. For religious reasons they refuse transfusion of whole blood or its primary components (red cells, fresh frozen plasma, platelets). OBJECTIVE This study aims to present the results obtained with Jehovahs Witnesses patients by a liver transplantation service. METHOD We conducted a retrospective review of medical records from Jehovahs Witnesses patients (n=4) who underwent orthotopic liver transplantation from September 2009 to September 2011 at the Walter Cantídio University Hospital of the Federal University of Ceará, Fortaleza, CE, Brazil. Coagulation parameters such as Hemoglobin, Hematocrit, Platelets, INR were evaluated during the preoperative, immediate postoperative, postoperative day (POD) 7 and POD 30. RESULTS Coagulation parameters were expressed as means: hematocrit, 35.07%±6.65%, 24.6%±4.74%, 19.85%±2.10%, 31.85%±5.99%; hemoglobin, 12.57 g/dL±2.22, 8.92 g/dL±1.75, 6.92 g/dL±0.58, 11.17 g/dL±0.9; platelets, 160,975 mm3±148000, 128,000 mm3±34836, 65,000 mm3±33496, 234,250 mm3±287003 and INR, 143±0.10, 2.4±0.34, 1.24±0.10, 1.14±0.09. CONCLUSION Liver transplantation can successfully be performed in Jehovahs Witnesses patient population provided that: 1) the medical team has extensive expertise in that field, 2) the patient has an adequate level of hematologic factors preoperatively, and 3) there is availability of specialized equipment such as cell saver to minimize blood loss and thus avoid transfusion requirements.

HEPATIC STEATOSIS ASSESSMENT: a comparative study between surgeon evaluation and forward histopathologic findings

CONTEXT Liver transplantation is one of the last viable resources for patients with end-stage liver disease. Many strategies are been used to improve the number of available organs and overcome waiting list delay. However, hepatic steatosis is one of the mainly concerns when organs are consider to transplantation due to it is importance as a risk factor for primary dysfunction. Surgeons play an important role to decide each organ will be accept or decline and its righteous allocation. OBJECTIVE Retrospectively evaluate the surgeon assessment of steatosis degree and its confrontation with further histopathologic findings. METHODS We analyzed 117 patients underwent deceased liver transplantation for end-stage liver disease in University Hospital Walter Cantideo, Fortaleza, CE, Brazil. A matrix table was organized to estimate the categorical data observed. We clustered the subjects into mild (0%-30%) and moderate (30%-60%) steatosis degree under the clinical criteria of organ suitability for transplantation. We categorized the organs as suitable organ for transplant and as non-suitable organ for transplant. Evaluations between the two first assessments, before perfusion (pre-perfusion) vs biopsy findings and after perfusion vs biopsy findings observations were analyzed and also a comparison between pre-perfusion and after perfusion data was performed. RESULTS On the first assessment, we obtained a 93% of agreement (n = 109) between the two evaluations. On the second assessment, we had an 8% (n = 9) of mistaken allocation. Comparing the observation before (pre-perfusion) and after (after perfusion), we obtained a strong agreement between the surgeons. CONCLUSIONS Although our experienced surgeon team, we have wrongly evaluated feasible organs for transplantation. Nonetheless, our faulty percentage is low comparing to worldwide percentage.

Liver transplantation for acute liver failure: a 5 years experience

BACKGROUND Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. AIM To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. METHODS A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease) scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. RESULTS Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2% at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. CONCLUSION Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients.

Hemophilia B acquired through liver transplantation

Hemophilia B is a sex-linked inherited bleeding disorder, with a frequency of 1 in 30,000 male births. Clinical manifestations are caused by defects in factor (F) IX production, leading to spontaneous or after trauma or surgery bleeding; treatment of acute bleeding episodes consists of parenteral FIX replacement. The first report of liver transplantation in a hemophiliac patient was in 1980, with normalization of FVIII production in a patient with hemophilia A. Many case reports subsequently have confirmed that liver transplantation restores both FVIII and FIX production and leads to clinical resolution of the coagulation defects. In contrast, hemophilia B acquired through liver transplantation has been previously reported only once. Herein, we describe the new onset of FIX deficiency, in association with mild coagulation abnormalities following liver transplantation, attributable to an unrecognized hemophilia B in the donor.

Ten-Year Experience With Liver Transplantation for Hepatocellular Carcinoma in a Federal University Hospital in the Northeast of Brazil

Hepatocellular carcinoma (HCC) is the most frequent and important primary liver tumor, with annual worldwide incidence of over 1 million cases, accounting for at least 500,000 deaths per year. The majority of cases of HCC occur in the setting of liver cirrhosis. In this retrospective, descriptive, and analytical study, between May 2002 and April 2012, 664 liver transplantations (LT) were conducted at a Federal University Hospital in the Northeast of Brazil, among which 140 LT were performed in patients with HCC. The tumor was more frequent in men with an average age of 56 years and infected with hepatitis C virus, many with a history of alcohol abuse. Alpha-fetoprotein was not useful in the diagnosis, and imaging methods have failed to diagnose the nodules in 19 patients (13.6%). Transarterial chemoembolization was the most-used bridging therapy to inhibit tumor growth for patients with HCC eligible for transplantation. The implementation of the Model for End Stage Liver Disease score in 2006 brought benefits to these patients. The rate of HCC recurrence after LT was 8.57% and occurred more often in the first 2 years after transplantation, with the liver graft being the most common site. Significant risk factors for recurrence were a long time on the LT waiting list, number of liver nodules over 3.5, and the presence of vascular invasion. In conclusion, LT for HCC leads to excellent long-term survival, with relatively few patients dying from tumor recurrence.

Alterações metabólicas induzidas por isquemia hepática normotérmica experimental e o efeito hepatoprotetor da ciclosporina

BACKGROUND: Hepatic transplantation is inevitably associated with periods of complete ischemia. However, the clamping of hepatic vascular pedicle is limited by the consequences of the post-ischemic injury to the liver. AIM: To determine the main metabolic alterations caused for the hepatic ischemia and the probable hepatoprotective effect cyclosporin. METHOD: Normothermic hepatic ischemia during 60 minutes was induced in the rats. The time-course (0, 1, 6, 24 hours) of changes in blood and in the hepatic concentrations of lactate, pyruvate, glucose, ketone bodies and in the ratio of acetoacetate/3-hydroxybutyrate, as well as the cytoplasmic and mitochondrial redox state of the liver cells were determined. A group of animals was daily pre-treated with cyclosporine (10 mg/kg) during 4 days until the induction of hepatic ischemia, then they studied 1 hour after hepatic revascularization. Hepatic ischemia caused elevation in the concentrations of lactate in the liver, suggesting that a pronounced level of anaerobic metabolism occurred during the ischemia period. Liver ischemia promoted yet a fall in the concentration and in the ratio of ketone bodies (acetoacetate/3-hydroxybutyrate) in the arterial blood in the studied period of one hour post-revascularization, perhaps reflecting impairment of ketogenesis as a result of the ischemic injury. CONCLUSION: The treatment with cyclosporine cause elevation in the concentration of ketone bodies and in the ratio of acetoacetate/3-hydroxybutyrate in the arterial blood 1 hour after reperfusion of the liver, suggesting that these drugs may accelerate the recovery of the ischemic hepatic lesion with reactivation of ketogenesis.