ABSTRACT
BACKGROUND: The cause of late graft dysfunction has not been elucidated. Although an antibody-mediated reaction is suspected as a potential mechanism, the target antigens have not been clarified. METHODS: To clarify the etiology of idiopathic posttransplantation hepatitis (IPTH), we simultaneously examined the presence of antibodies that react with liver tissue (ARLT) by means of indirect immunofluorescence staining, as well as the presence of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA). A subanalysis of the IPTH group was also performed. Within the IPTH group, the correlation between ARLT titer and clinical data were analyzed. RESULTS: In the sera of patients with IPTH (30 patients), ARLT were found at a significantly higher frequency than in patients without IPTH (42 patients; P < 0.001). Moreover, the ARLT titer appeared to be correlated with the severity of hepatitis or hepatic injury. In contrast, the frequency of HLA-DSA was significantly lower in patients with IPTH than in patients without IPTH (P = 0.001). CONCLUSION: Our findings indicate that ARLT, and not HLA-DSA, profoundly influence the etiology of IPTH.
Subject(s)
Autoantibodies/blood , Graft Rejection/immunology , HLA Antigens/immunology , Hepatitis/immunology , Isoantibodies/blood , Liver Transplantation , Postoperative Complications/immunology , Adolescent , Animals , Biomarkers/blood , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Hepatitis/diagnosis , Humans , Infant , Male , Postoperative Complications/diagnosis , Rats , Rats, WistarABSTRACT
AIM: To analyze the risks of preoperatively produced donor-specific antibody (DSA) in liver transplantation. METHODS: DSA was assessed using direct complement-dependent cytotoxicity (CDC) and anti-human globulin- (AHG-) CDC tests, as well as the Luminex Single Antigen assay. Among 616 patients undergoing blood type identical or compatible living donor liver transplantation (LDLT), 21 patients were positive for CDC or AHG-CDC tests, and the preserved serum from 18 patients was examined to determine targeted Class I and II antigens. The relationships between the mean fluorescence intensity (MFI) of DSA and the clinical outcomes were analyzed. RESULTS: Patients were divided into 3 groups according to the MFI of anti-Class I DSA: high (11 patients with MFI > 10,000), low (2 patients with MFI < 10,000), and negative (5 patients) MFI groups. Six of 11 patients with high Class-I DSA showed positive Class-II DSA. Hospital death occurred in 7 patients of the high MFI group. High MFI was a significant risk factor for mortality (P = 0.0155). Univariate analysis showed a significant correlation between MFI strength and C4d deposition (P = 0.0498). CONCLUSIONS: HLA Class I DSA with MFI > 10,000 had a significant negative effect on the clinical outcome of patients with preformed DSA in LDLT.
Subject(s)
Cytotoxicity Tests, Immunologic , Immunoassay , Isoantibodies/analysis , Liver Transplantation/mortality , Living Donors , Adolescent , Adult , Analysis of Variance , Child , Female , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Histocompatibility Testing , Humans , Infant , Isoantibodies/immunology , Male , Middle Aged , Survival AnalysisABSTRACT
The goals of this study were to evaluate the incidence of hepatic venous outflow obstruction (HVOO) in pediatric patients after living donor liver transplantation (LDLT) using left-sided lobe grafts and to assess the therapeutic modalities used for the treatment of this complication at a single center. Four hundred thirteen primary LDLT procedures were performed with left-sided lobe grafts between 1996 and 2006. All transplants identified with HVOO from a cohort of 380 grafts with survival greater than 90 days were evaluated with respect to the patient demographics, therapeutic intervention, recurrence, and outcome. Seventeen cases (4.5%) were identified with HVOO. Eight patients experienced recurrence after the initial balloon venoplasty. Two patients finally required stent placement after they experienced recurrence shortly after the initial balloon venoplasty. A univariate analysis revealed that a smaller recipient-to-donor body weight ratio and the use of reduced grafts were statistically significant risk factors. The cases with grafts with multiple hepatic veins had a higher incidence of HVOO. In conclusion, the necessity of repeated balloon venoplasty and stent placement was related to poor graft survival. Therefore, the prevention of HVOO should be a high priority in LDLT. When grafts with multiple hepatic veins and/or significant donor-recipient size mismatching are encountered, the use of a patch graft is recommended. Stent placement should be carefully considered because of the absence of data on the long-term patency of stents and stent-related complications. New stenting devices, such as drug-eluting and biodegradable stents, may be promising for the management of HVOO.
Subject(s)
Budd-Chiari Syndrome/etiology , Liver Transplantation/adverse effects , Living Donors , Universities , Adolescent , Budd-Chiari Syndrome/epidemiology , Budd-Chiari Syndrome/therapy , Catheterization/instrumentation , Chi-Square Distribution , Child , Child, Preschool , Female , Graft Survival , Humans , Incidence , Infant , Infant, Newborn , Japan , Kaplan-Meier Estimate , Male , Prosthesis Design , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Stents , Time Factors , Treatment OutcomeABSTRACT
INTRODUCTION: Thrombotic microangiopathy (TMA) is a complication occurring after liver transplantation (LT), and an unusually large multimer (ULM) of Von Willebrand factor (VWF) and ADAMTS13 may play an important role in the onset of TMA during LT. MATERIAL AND METHODS: Eight-one patients underwent living donor LT (LDLT). Seventeen of those patients had both severe thrombocytopenia and hemolytic anemia with fragmented red cells and were diagnosed as TMA- like syndrome (TMALS). RESULTS AND CONCLUSIONS: A significant reduction of ADAMTS13 and an increase of VWF were observed in the patients with TMALS. The ADAMTS13 activity in patients after LDLT was significantly reduced from day 1 to day 21, and it was significantly low in those with TMALS at day 14 and 28. The VWF levels in patients with LDLT were significantly high, and the VWF/ADAMTS13 ratio was significantly increased in patients at 7, 14 and 28 days after LDLT, especially in patients with TMALS at day 14 and 28 after LDLT. High molecular weight multimers of VWF were observed to have increased in patients with LDLT, and the high molecular weight multimers of VWF were further increased in those with mild TMALS but they decreased in those with severe TMA. These findings suggest that ULM- VWF and ADAMTS13 might be associated with the onset of TMA after LT.
Subject(s)
ADAM Proteins/blood , Liver Transplantation/adverse effects , Thrombotic Microangiopathies/blood , Thrombotic Microangiopathies/etiology , ADAMTS13 Protein , Aged , Child , Female , Humans , Male , Middle Aged , von Willebrand Factor/metabolismABSTRACT
Thrombotic microangiopathy (TMA) or thrombotic thrombocytopenic purpura (TTP) is a life-threatening syndrome characterized by increased number of fragmented red cells (FRCs) and thrombocytopenia. FRCs can be measured using the recently developed automated hematology analyzer XE-2100. The normal range for FRCs is 0% to 0.205%, as determined by the automated hematology analyzer XE-2100. The FRC count is significantly elevated in patients with TMA associated with liver transplantation, bone marrow transplantation, or TTP. In patients with TMA after liver transplantation, the FRC count is significantly higher than in those without TMA. In receiver operating characteristic analysis for the diagnosis of TMA, the area under the curve is 0.986, suggesting that FRC is a useful marker for the diagnosis of TMA. When the cutoff value of FRC for TMA is 1.2%, the sensitivity is 90% and the specificity is 96%, indicating that FRC is the most useful screening test for the diagnosis of TMA.
