The presence of B-cell nodules does not necessarily portend a less favorable outcome to therapy in patients with acute cellular rejection of a renal allograft.

The presence of B-cell nodules in kidney biopsies of patients undergoing acute renal allograft rejection has been reported to be associated with glucocorticoid resistance and a high risk of graft failure. In an attempt to corroborate this observation, biopsies of renal transplants that evidenced Banff grade I A acute rejection were examined for the presence of B- or T-cell nodules, the detection of which was correlated with the therapeutic response. Biopsies from 14 consecutive renal transplant recipients with a diagnosis of acute cellular rejection were examined for the presence of T (CD3-positive) or B (CD20-positive) cells by immunohistochemistry. All patients were biopsied because of a rise in serum creatinine. No biopsy showed evidence of acute humoral rejection. Immunofluorescence microscopy was negative for C4d deposition in peritubular capillaries. There were no neutrophils in the peritubular or glomerular capillaries. Five patients had T-cell nodules; four had B-cell nodules; three had both T- and B-cell nodules; two had no nodules. All biopsies contained CD3-positive cells in the tubules and in the interstitium. In all but one of the patients, episodes of acute rejection were treated with steroids (one received thymoglobulin). Furthermore two patients received mycophenolate mofetil and one, sirolimus. There were no significant differences among the groups in either the initial creatinine or the creatinine after therapy. The presence of B-cell nodules in renal allograft biopsies of patients experiencing acute cellular rejection did not portend a less favorable outcome.

c-Kit-positive mast cells in portal tracts cannot be used to distinguish acute cellular rejection from recurrent hepatitis C infection in liver allografts.

Cirrhosis secondary to chronic hepatitis C virus (HCV) is the most common indication for liver transplantation. Recurrence of HCV infection in the liver allograft occurs at a high rate. The differentiation of recurrent HCV infection from acute cellular rejection (ACR) represents a difficult challenge in transplantation pathology. The c-Kit receptor is a tyrosine kinase membrane protein encoded by the c-Kit proto-oncogene, which is expressed on mast cells and on hematopoietic stem and progenitor cells. Mast cells are important effector cells of a broad range of immune responses. Recently, c-Kit+ mast cells were shown to form part of the inflammatory infiltrate in acute liver allograft rejection. A strong relationship was found between c-Kit+ cell densities and increasingly severe rejection. The present study sought to determine whether the presence of c-Kit+ cells could be used to distinguish between ACR and recurrent HCV in liver allografts. Immunohistochemical staining for c-Kit was performed on 20 transplant biopsy specimens from 10 patients with mild to moderate ACR and 10 other patients with recurrent hepatitis C. The number of c-Kit+ cells per portal tract varied with the density of the overall inflammatory infiltrate. There was no significant difference between the number of c-Kit+ cells in the biopsy specimens that carried a diagnosis of ACR and those from patients who had been diagnosed as having recurrent HCV. It was concluded that immunohistochemical staining for the presence of c-Kit+ mast cells cannot be used to differentiate between ACR and recurrent HCV infection in liver allograft biopsy specimens.

Basiliximab induction in adult liver transplant recipients with 93% rejection-free patient and graft survival at 24 months.

Induction with the use of interleukin-2 receptor monoclonal antibodies may avoid many of the adverse events associated with polyclonal antibodies and significantly impact on rejection-free long-term survival in orthotopic liver transplantation (OLTx). We describe our experience with the use of basiliximab induction therapy in adult OLTx recipients on tacrolimus-based immunosuppression. Forty-six consecutive deceased donor primary OLTx were analyzed. All patients received standard doses of basiliximab, tacrolimus, and steroids. Mycophenolate mofetil was also used as indicated. The mean follow-up period was 17.9 months. Forty-three patients remained rejection-free during follow-up. The actuarial patient and graft survival rate at 2 years was 93%. The rate of histology-proven hepatitis C virus (HCV) recurrence was 24%, with two progressing to severe cholestatic recurrent HCV. None of the study patients developed (cytomegalovirus (CMV) infection or posttransplant lymphoproliferative disease (PTLD). Results were compared to a historical group of 46 OLTx recipients on tacrolimus-based immunosuppression without basiliximab induction. The historical group had a rejection rate of 34% with lower patient and graft survival rates of 71.74% and 69.5%, respectively, at 24 months as well as a higher histological HCV recurrence rate of 77% (17/22), with three patients progressing to graft failure within 2 years. CMV infection and disease developed in 4.5% of the patients. Although PTLD was not observed, three recipients with hepatocellular carcinoma (HCC) developed and died of metastatic HCC. Induction with basiliximab in combination with tacrolimus-based immunosuppressive regimen reduces the incidence of rejection and improves rejection-free survival rate after OLTx without increasing the incidence of CMV, PTLD, or HCV recurrence.

Hepatic artery thrombosis after orthotopic liver transplantation.

OBJECTIVE: Hepatic artery thrombosis after liver transplantation is uncommon, but represents an important cause of morbidity and mortality. The aim of this study is to identify the possible risk factors for the development of hepatic artery thrombosis, and the impact of hepatic artery thrombosis on the patients and graft survival. METHODS: Between January 1994 and June 1998, we reviewed retrospectively a series of 86 liver transplant procedures performed on 81 adult patients. Arterial anomalies of the donor graft, rejection episodes, cold ischemia time, ABO matching, the use of blood/fresh frozen plasma during and after surgery, and the use of heparin as prophylactic anticoagulation therapy were examined as a possible contributing risk factors for the development of hepatic artery thrombosis. RESULTS: Hepatic artery thrombosis occurred in 7 procedures out of 86 (9%). Early cases of Hepatic artery thrombosis within 15 days after transplant occurred in 4 patients. Late thrombosis occurred in 3 patients. Analysis of potential risk factors for the development of hepatic artery thrombosis was carried out. Five out of 40 patients who did not received prophylactic heparin had hepatic artery thrombosis (12.5%), while only 2 out of 46 patients who received prophylactic heparin had hepatic artery thrombosis 4%. On the other hand, 6 out of the 7 patients developed hepatic artery thrombosis received more than 5 units of blood transfusion during the transplant procedure (11%) while only one patient developed hepatic artery thrombosis who received less than 5 units intra-operatively (3%). Management of hepatic artery thrombosis cases were carried out in the form of: thrombectomy (n = 1), thrombectomy followed by retransplantation (n = 2), and non-surgical or conservative treatment (n = 4). The overall survival rate was (43%) (3 out of 7). Out of four deaths, 3 were directly related to hepatic artery thrombosis while the cause of death iin the remaining patients was attributed to pulmonary sepsis. CONCLUSION: Early hepatic artery thrombosis leads to death unless quick retransplantation follows. Conservative treatment for the late onset hepatic artery thrombosis on occasion has been useful. The use of postoperative prophylactic anticoagulation therapy might be of benefit in the prevention of hepatic artery thrombosis after liver transplantation. Increased transfusion requirement for red blood cells during transplant procedure was independently associated with increase incidence of hepatic artery thrombosis.

Brain abscess in solid organ transplant recipients receiving cyclosporine-based immunosuppression.

OBJECTIVE: To determine the incidence, clinical presentation, and outcome and confounding factors associated with the development of a brain abscess in solid organ transplant recipients. DESIGN: A 14-year retrospective survey. SETTING: A single, multiorgan, academic transplantation center. PATIENTS: A total of 2380 liver transplant recipients, 1650 kidney transplant recipients, and 598 heart, heart-lung, or lung transplant recipients of all ages (pediatric and adult) were included. All patients were given cyclosporine-based immunosuppression during this period. MAIN OUTCOME MEASURE: A brain abscess was determined to be present it there was histological and/or microbiological confirmation of a brain lesion seen by a computed tomographic scan. A brain abscess was considered suspicious if radiographic findings were seen in the clinical setting of neurologic symptoms and fever without histological or microbiological confirmation. RESULTS: A brain abscess developed in a total of 28 patients (0.61%) of the total study population. The frequency of brain abscess according to organ type was as follows: 0.63%, liver; 0.36%, kidney; and 1.17%, heart and heart-lung. The overall mortality was 86%. Complicating factors associated with fungal (Candida and Aspergillus sp) abscess formation included major subsequent operations, retransplantations, antirejection therapy, associated bacteremia or viremia, and multiorgan failure. The lung was the primary site of dissemination in 18 patients. Low-dose prophylactic amphotericin was ineffective in preventing a fungal brain abscess in 10 high-risk patients. Because of the ineffective therapy and the deadly nature of established fungal abscesses, full-dose antifungal therapy and reduced immunosuppression were warranted on identification of a high-risk clinical setting. Nonfungal abscesses (Nocardia and Toxoplasma sp) occurred in healthy graft recipients long after transplantation. The existing medical therapy is usually effective in these patients, provided that rapid tissue diagnosis is established. CONCLUSIONS: The epidemiological features of brain abscess formation after solid organ transplantation suggest 2 populations of patients exist that differ in timing, clinical setting, and response to therapy. For the chronically immunosuppressed outpatient, an established abscess should be empirically treated with sulfonamides until tissue diagnosis is confirmed. On the other hand, the acutely immunosuppressed posttransplant recipient, with defined risk factors, should receive full-dose therapy with amphotericin B and concomitantly lowered immunosuppression.

Biliary stones and sludge in liver transplant patients: a 13-year experience.

PURPOSE: To determine the prevalence, radiologic features, and clinical significance of bile duct filling defects (BDFDs) in liver transplant recipients studied with cholangiography. MATERIALS AND METHODS: During 13 years, 4,100 cholangiograms were obtained in 1,650 patients. All studies showing BDFD suggestive of stones, sludge, cast, or necrotic debris were retrospectively evaluated. RESULTS: The prevalence of BDFD was 5.7% (n = 94). On the basis of cholangiographic appearance, BDFDs were categorized as sludge or cast in 53 grafts (56%), stones in 32 (34%), and necrotic debris in nine (10%). Forty-three patients (46%) underwent surgical biliary reconstruction, while 14 (15%) underwent interventional radiologic treatments. Twenty-four of 32 stones (75%) were treated with surgical reconstruction, compared with 31% (19 of 62 grafts) of other BDFDs (P < .0001). Necrotic debris and sludge were associated with hepatic artery occlusion in seven of nine (78%) and 16 of 53 (30%) grafts, respectively. CONCLUSION: Stones and sludge are relatively infrequent after liver transplantation but are associated with high morbidity. Surgical or interventional radiologic treatments are usually performed. Bile duct stones are usually treated with surgical biliary reconstruction. While debris and bile duct necrosis are due to ischemia from hepatic artery occlusion, sludge may also have an ischemic pathogenesis in some cases.