Pre- and posttransplant monitoring of alloantibodies by complement-dependent cytotoxicity and luminex methodologies in liver transplantation.

BACKGROUND: This study evaluated the influence of circulating anti-HLA antibodies on outcomes of 97 liver allografts from deceased donors. METHODS: Human leukocyte antigen (HLA) antibody screening was performed by both complement-dependent cytotoxicity (CDC) and multiparameter Luminex microsphere-based assays (Luminex assay). RESULTS: The agreements between T- and B- cell CDC and Luminex assays were 67% and 77% for pre- and posttransplant specimens, respectively. Graft dysfunction was not associated with either positive pretransplant CDC or Luminex panel-reactive antibody (PRA) values. Likewise, positive posttransplant T- or B- cell CDC PRA values were not associated with graft dysfunction. In contrast, posttransplant Luminex PRA values were significantly higher among patients with graft dysfunction compared with subjects with good outcomes (P = .017). CONCLUSION: Posttransplant monitoring of HLA antibodies with Luminex methodology allowed identification of patients at high-risk for poor graft outcomes.

Case report of hepatic mucormycosis after liver transplantation: successful treatment with liposomal amphotericin B followed by posaconazole sequential therapy.

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SOT), with a cumulative incidence of around 2% during the first year after SOT. The associated mortality rate is high, and surgical debridement is frequently required as part of the treatment along with antifungal therapy based mostly on amphotericin B formulations, We describe here an unusual case of hepatic mucormycosis in a liver transplant recipient that was successfully treated with clinical therapy based on liposomal amphotericin B followed by posaconazole, without surgical resection.

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

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.

Phenotypic expression of familial amyloid polyneuropathy in Brazil.

Familial amyloid polyneuropathy (FAP) is an inherited amyloidosis mainly associated with transthyretin Val30Met variant. Clinical heterogeneity has been reported in different populations with FAP and Va130Met variant. In order to characterize FAP expression in Brazilians and to compare its features to those reported in other cohorts, 44 Brazilian patients (27 females, median age 36 [23-53] years) with FAP and the Val30Met variant were investigated. Approximately 40% of their family members, with the exception, of parents and siblings, had FAP. Most of the patients had symptoms of peripheral neuropathy at onset. Median age at onset was 32 [20-44] years. Earlier onset was observed in males (27 [20-43] years in males vs. 33 [20-44] years in females, P = 0.02) and in patients whose parents had FAP (31 [20-44] years vs. 40 [37-43] years in patients, respectively with and without affected parents, P = 0.03). Phenotypic expression of FAP in Brazil is similar to the one reported in Portugal, characterized by high disease penetrance, early onset, particularly in males and in subjects with affected parents, and major symptoms of peripheral neuropathy. These data highlight the influence of common genetic factors, shared by both groups of patients, in disease expression.

Anesthetic management of liver transplantation in patients with fulminant hepatic failure: case reports.

Fulminant hepatic failure (FHF), although not frequent, produces a high mortality rate of 70% to 90%. This study describes the management of FHF patients without the use of any intracranial pressure monitoring device.

Subcapsular hematoma of the graft after liver transplantation.

Subcapsular hematoma of the graft is an underreported complication of liver transplantation (LT). Among 408 LT performed from September 1, 1985, to September 1, 2000, eight patients developed a subcapsular hematoma within 30 days after LT (8/408 = 2.0%). Among the six early cases observed, five required further surgical approaches due to hematoma progression, rupture, and hemorrhage. One patient underwent liver retransplantation due to uncontrollable hepatic hemorrhage. The two more recent cases were successfully treated by early opening of the Glisson's capsule with hemostasis of the hepatic raw bleeding surface. The five patients who developed acute renal failure required dialysis. Three patients died during hospitalization. Among the survivors, two were discharged on the postoperative (PO) day 15; the others on PO day 37, 38, and 56. In conclusion, subcapsular hematoma of the graft is a potentially serious complication of LT that may produce severe hemorrhage, shock, and in extreme cases, graft loss or even death. The severity of the complication is related to the extension of the decapsulated area of the graft. An early surgical approach with intentional opening of the hematoma before progression of the lesion seems to facilitate hemostasis and improve results.

Improved clinical outcomes for liver transplant recipients using cyclosporine monitoring based on 2-hr post-dose levels (C2).

BACKGROUND: A prospective, open-label, study was conducted at 29 centers in 9 countries, involving 307 de novo liver transplant patients to compare the clinical usefulness of monitoring 2-hr post-dose cyclosporine (CsA) levels (C2) with conventional trough cyclosporine blood levels (pre-dose) (C0). METHODS: Neoral oral therapy was initiated at 15 mg/kg/day and dose adjusted according to predetermined C2 or C0 target level ranges. The primary efficacy variable was treatment failure at 3 months, where evaluation was based on a composite endpoint of biopsy-proven rejection, treatment for rejection, graft loss, death, or premature withdrawal/discontinuation from the study. RESULTS: Baseline characteristics were similar between groups. Graft loss at 12 weeks (retransplantation or death) occurred in 6.8% C2 and in 7.0% C0 patients. Overall incidence of treated acute rejection was lower for C2 (23.6%) than C0 patients (31.6%) (P=0.144, Cochran-Mantel-Haenszel [CMH] test). In hepatitis C virus (HCV)-negative patients, the incidence of rejection in the C2 group was significantly less than in the C0 group (21.2% vs. 33.0%; P<0.05), whereas in HCV-positive patients, the rejection rate was similar in both groups (26.7% for C2 group vs. 27.3% for C0 group: P=0.81). C2 patients (n=16) who reached minimum target CsA levels by day 3 had a notably low incidence of rejection (12.5%), whereas there was no difference in the incidence of rejection in C0 patients, irrespective of time to reach target level. For biopsy-proven acute rejections (21.6% for C2 vs. 30.4% for C0), the incidence of moderate and severe histological diagnosis was significantly lower in the C2 group than in the C0 group (47% vs. 73%; P=0.01). Safety profiles were similar between the two groups, with few patient withdrawals due to adverse events (9.5% for C2; 7.0% for C0). CONCLUSIONS: Using C2 monitoring, the overall incidence of acute cellular rejection was lower compared with the C0 group, and the histological severity of acute rejections was shown to be significantly milder for the C2 group, indicative of good long-term prognosis. These data demonstrate that the use of C2 monitoring is superior to C0 and results in a reduction in the incidence and severity of acute cellular rejection without detrimental effect on the drug safety profile.

Human polyclonal anti-hepatitis B surface antigen immunoglobulin reduces the frequency of acute rejection after liver transplantation for chronic hepatitis B.

BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 +/- 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.

Familial amyloidotic polyneuropathy type 1 in Brazil is associated with the transthyretin Val30Met variant.

UNLABELLED: Familial amyloidotic polyneuropathy type 1 (FAP1) is an inherited systemic amyloidosis that is secondary to the deposition of transthyretin (TTR) variants in peripheral nerves and in certain visceral organs. More than 50 distinct mutations have already been described in the TTR gene. Yet, the most common mutation found worldwide is a substitution of valine for methionine in position 30 (Val30Met). Currently, the variants of TTR in Brazilian FAP1 patients remain largely unknown and the aim of this study was to analyze the frequency of the TTR Val30Met mutation in such Brazilian subjects. METHODS: Thirty-two FAP1 patients belonging to 24 different families were studied for the presence of Val30Met variant by PCR-RFLP. RESULTS: All Brazilian FAP1 subjects studied were positive for the TTR Val30Met variant. As expected, all of them were heterozygous for the mutation. CONCLUSION: TTR Val30Met mutation was the sole TTR variant found in Brazilian FAP1 patients in this cohort, and it was present even in those subjects without a clear history of Portuguese ancestry.