Diagnostic Accuracy of Transient Elastography for Detecting Liver Fibrosis After Liver Trannsplantation: A Specific Cut-Off Value Is Really Needed?

INTRODUCTION: Liver transplant recipients often perform liver biopsy (LB), specially in the context of potentially recurring diseases, such as hepatitis C infection. However, the LB has risks of complications, despite being the gold standard. Transient elastography (TE) is a noninvasive method comparable to the LB to evaluate liver fibrosis in various settings, but its accuracy among transplant recipients is not fully understood. OBJECTIVE: To determine the accuracy of TE in liver transplant recipients compared with LB to successfully predict liver fibrosis. PATIENTS AND METHODS: Patients who underwent liver transplantation at Hospital Israelita Albert Einstein from 2010 to 2012 and presented with LB indication were also subjected to TE at the time of LB. The medium value of ten successful measurements was kept as a representative of the liver stiffness. The definition of cut-off points was made to ensure specificity of ≥90 % for all fibrosis stages (F0-F4). RESULTS: LB was performed in 267 patients. TE was not analyzed in only 8 (3 %) due to an elevated body mass index. The optimal liver stiffness cut-off value and diagnostic performance were 8.1 kPa for F ≥ 1, 12.3 kPa for F ≥ 2, 15.1 for F ≥ 3, and 16.7 for F = 4 for all patients and were 8.1 kPa for F ≥ 1, 12.3 kPa for F ≥ 2, 16.5 for F ≥ 3, and 17.6 for F = 4 for patients with hepatitis C. CONCLUSIONS: TE demonstrated good performance in defining cut-off points for fibrosis on liver histology observed in transplant recipients. The TE can be considered an alternative to LB in post-liver transplantation.

List and liver transplant survival according to waiting time in patients with hepatocellular carcinoma.

The time that patients with hepatocellular carcinoma (HCC) can safely remain on the waiting list for liver transplantation (LT) is unknown. We investigated whether waiting time on the list impacts transplant survival of HCC candidates and transplant recipients. This is a single-center retrospective study of 283 adults with HCC. Patients were divided in groups according to waiting-list time. The main endpoint was survival. The median waiting time for LT was 4.9 months. The dropout rates at 3-, 6-, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Mortality on the list was 4.8%, but varied depending of the time on the list. Patients who waited less than 3-months had an inferior overall survival when compared to the other groups (p = 0.027). Prolonged time on the list significantly reduced mortality in this analysis (p = 0.02, HR = 0.28). Model for End Stage Liver Disease (MELD) score at transplantation did also independently impact overall survival (p = 0.03, HR = 1.06). MELD was the only factor that independently impacted posttransplant survival (p = 0.048, HR = 1.05). We conclude that waiting time had no relation with posttransplant survival. It is beneficial to prolong the waiting list time for HCC candidates without having a negative impact in posttransplant survival.

Clinical profile and liver explant findings in patients with and without pretransplant downstaging for hepatocellular carcinoma.

INTRODUCTION: Since August 2010, The Brazilian National Transplantation System has allowed performance of liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) who have been successfully treated with preoperative downstaging (DS). Herein we sought to compare the clinical profiles and liver explant findings among patients with versus without preoperative DS. METHODOLOGY: Prospective cohort of patients with HCC within and beyond the MC undergoing OLT. Patients were considered for DS if they were beyond the MC without evidence of vascular invasion or extrahepatic disease. Transcatheter arterial chemoembolization was used for DS, which was considered to be successful if the MC were achieved at any moment during the follow-up. RESULTS: Between May 2006 and May 2010, we performed 130 OLTs in HCC patients, among whom 10 received preoperative DS. Both groups were comparable for gender, age, viral etiology, serum levels of alpha fetoprotein, and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores (P > .05). The liver explants were within the MC in 80% of patients with preoperative DS and 90% of those without preoperative DS. They were comparable for the number of HCC nodules, total tumor size, histologic grade, and presence of microvascular invasion. Patients with pretransplant DS showed larger HCC nodules (33.3 ± 9.65 vs 26.3 ± 9.62 mm; P .029) and more frequent macrovascular invasion (1 vs 1 patient, P = .024). CONCLUSION: Preoperative DS for unresectable HCC may provide a curative treatment for patients who would otherwise be candidates for palliative therapy only. The baseline characteristics and liver explant findings were similar in both groups. We have yet to determine whether the differences observed regarding the size of the largest nodule and the higher frequency of macrovascular invasion have an impact on outcome.

Hepatocellular carcinoma recurrence among liver transplant recipients within the Milan criteria.

INTRODUCTION: Orthotopic liver transplantation (OLT) is an excellent option for patients with unresectable hepatocellular carcinoma (HCC) within the Milan criteria. Recurrence of HCC has a severe impact on post-OLT survival. In this study, we performed an analysis of post-OLT recurrence pattern of HCC. METHODS: The prospective cohort of OLT patients included those with unresectable HCC within the Milan criteria, and those beyond the Milan criteria who were downstaged with transcatheter arterial embolization until they achieved the Milan criteria. RESULTS: Between May 2006 and May 2011, we performed 130 OLT for unresectable HCC within the Milan Criteria among whom 9 patients (6.9%) experienced tumor recurrence. Two (22.2%) had undergone preoperative downstaging. At the time of OLT, mean serum alpha-fetoprotein levels were 623.8 ± 682.9 ng/mL. The liver explants showed 7 (77.8%) subjects were within the Milan criteria, with an average 2.6 ± 2.2 tumors, most of which (89%) were moderately differentiated. Microvascular and macrovascular invasion were observed in 5 (55.6%) and 2 (22.2%) cases, respectively. Liver explants were beyond the Milan criteria in both patients who had undergone preoperative downstaging. Recurrence occurred 23.1 ± 14.3 months after OLT, having been detected in the liver (n = 3; 33.3%), lung (n = 3; 33.3%), brain, peritoneum, and adrenal gland (n = 1 each; 11.1% each). Mean survival after detection of recurrence was 137.4 ± 96.4 days. CONCLUSIONS: Despite strict candidate selection criteria, HCC recurrence may occur after OLT, bearing a significant impact on posttransplant outcomes to optimize results requires refinements in candidate selection, as well as well-defined cost-effective post-OLT surveillance protocols.

Results of retransplantation for primary nonfunction in a single center.

INTRODUCTION: Early graft dysfunction has a negative impact on allograft and patient survivals, evolving to retransplantation or death in the majority of cases. The outcome of a second liver transplant is usually worse than the first procedure. Considering the increasing number of recipients on the waiting list, and the discrepancy between the number of accessible donors and recipients, we sought to analyze the results of retransplantation at our institution and at those within the State of Sao Paulo. METHODS: We reviewed the data of 419 deceased donor transplants on 367 patients from June 2005 to April 2010. Twenty-three patients underwent retransplantation due primary nonfunction (PNF) or early graft dysfunction. The following variables were studied: age, gender, disease that lead to the first transplant, Model for End-Stage Liver Disease (MELD) score on the day before the retransplantation, intensive care unit (ICU) length of stay, and duration of orotracheal intubation (OTI). We compared our patient survival at 30 days and 1 year with that of other patients undergoing retransplantation due to PNF in the Sao Paulo State during the same period. RESULTS: The majority of patients were females (60.87%), with a mean age of 44.6 years. The etiology that led to our first transplantation was cirrhosis due to hepatitis C virus (HCV; n = 6), followed by acute liver failure, (n = 5). The average of ICU stay was 15.08 days (range, 5-45). The mean MELD score was 34.43 (range, 19-50). The survival was 73.92% and 60.78% at 30 days and 1 year postretransplantation, respectively, whereas for São Paulo State, it was 63.04% and 51.63%, respectively.

Antibody-mediated rejection: hyperacute rejection reality in liver transplantation? A case report.

Hyperacute rejection is rare among ABO-compatible liver transplantations. The mechanism is donor preformed antibodies causing graft loss within a few days. Herein, we have described a case of an ABO-compatible liver transplantation that underwent hyperacute rejection, needing retransplantation for treatment. A 27-year-old man of blood group A positive who displayed fulminant hepatic failure due to hepatitis B (in agreement with the O'Grady criteria), received an ABO-compatible graft. He developed significant asthenia, fever, hypotension, oliguria, and coagulopathy. Ultrasonography revealed total thrombosis of the portal vein and absence of dilatation of bile ducts. The patient was priorized for retransplantation and underwent a good subsequent evolution. On anatomopathologic exam the explant revealed thrombosis of the intrahepatic branches of the portal vein with venous and ischemic infarcts compatible with a diagnosis of hyperacute rejection. The clinical findings of hyperacute rejection were characterized by progressive elevation of bilirubin and thrombocytopenia associated with signs of hepatic failure during the first days after transplantation. In this case, the histological exam was compatible with hyperacute rejection, excluding the diagnoses of hepatic artery thrombosis or biliary obstruction, despite the negative test for anti-HLA antibodies. The diagnosis of hyperacute rejection could be made associated with a short ischemic time and a good response after retransplantation.

Twenty years of liver transplantation in Brazil.

This paper summarizes the 20 years of liver transplantation in Brazil, in the context of the Western world scenario. More than 5000 liver transplantations have been performed in the country since September 1, 1985. The living-donor liver transplantation, one of the landmarks in liver transplantation, was first described by our team in 1989. Brazil is the seventh country in number of liver transplants in the Western world and the first in Latin America. Almost 1000 procedures were performed in 2004, 19% of them involving living donors.