Heart transplantation using donors positive for hepatitis

From May 1994 to September 2003, 177 hearts were procured for heart transplantation (HTx) from donors ranging in age from 1 year 2 months to 66 years 5 months (mean = 30 years). All donors and recipients received serologic tests for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), and hepatitis C virus antibody (anti-HCV). Thirty-two donors were HBsAg-positive and another four were anti-HCV-positive. Two HBsAg-positive donors were transplanted to patients with no previous evidence of hepatitis. After HTx, one received hepatitis B immunoglobulin prophylaxis and no hepatitis was noted during a 5 years follow-up. The other seroconverted at 4 months after HTx, requiring lamivudine treatment. Another four HBsAg-positive donors were transplanted to HBsAg-positive recipients. All four recipients had hepatitis flare-ups requiring lamivudine treatment. The other 26 HBsAg-positive donors were transplanted to anti-HBs-positive recipients. None suffered from hepatitis. Among the four patients receiving anti-HCV-positive hearts, seroconversion was noted in one recipient at 26 months. This patient never had clinical hepatitis before he died of allograft rejection at 3 years after HTx. The other three recipients remain anti-HCV negative during follow-up of 80, 50, and 46 months. It was concluded the hepatitis B- or C-positive donors could be used as heart donors for status 1 patients. Donors with positive HBsAg may be transplanted to anti-HBs-positive recipients with no HBV infection.     

Strategies for Maximizing Heart and Lung Transplantation Opportunities in Japan

Introduction

Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors.

Method

Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function.

Results

Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%.

Conclusion

Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities.     

Medium-term results of heart transplantation using donors over 63 years of age

BACKGROUND: The continual shortage of hearts for transplantation (HTx) led to the expansion of the donor pool by accepting older donors. We compared the medium-term follow-up of patients after HTx with older hearts (over the age of 63 years) with those of patients after HTx with younger hearts. PATIENTS AND METHODS: Since April 1994 we have used hearts for HTx from donors older than the age of 63 years. Until November 1998, 309 HTx and 9 re-HTx were performed in 309 adults with a mean age of 50.7+/-10.9 years (range 17-68 years). There were 252 men and 57 women. The patients were divided into two groups: group I--donor age under 63 years (296 patients, mean age 50.4+/-11 years; mean donor age 38.1+/-13 years; mean follow-up 1.7+/-1.6 years); group II-donor age of more than 63 years (13 patients, mean age 57.4+/-5.6 years; mean donor age 65.1+/-2.1; mean follow-up 2.2+/-1.6 years). There were no differences in the etiology of heart failure, gender, or ischemia time between the groups. The patients in group II were significantly older (P = 0.008). Multiple factors were analyzed in the groups, which included changes in the left/right ventricle ejection fraction, early postoperative mortality (up to 30 days), cumulative survival rates and cardiac-dependent morbidity [myocardial infarction, malignant arrhythmias, coronary stenosis (>50% in one of the main coronary arteries) and transplant vasculopathy]. Additionally, freedom from cytomegalovirus infection (rise of titer or seroconversion) and freedom of acute rejection episodes grade > or =2 (International Society of Heart & Lung Transplantation [ISHLT]) were analyzed. RESULTS: After 1 year mean left and right ventricle ejection fraction were good in both groups and did not significantly change for up to 2 years. No Re-HTx was performed in group II. The early postoperative mortality was similar in both groups (P = 0.8). Also, the cumulative survival rates were similar in both groups (P = 0.87). Long-term cardiac morbidity was lower in group I (P = 0.03). The long-term freedom from cytomegalovirus infection in group I was significantly higher when compared with group II (P = 0.0002). The long-term freedom from severe rejection episodes was similar in both groups (P = 0.3) CONCLUSION: The study found a significant increase in long-term cardiac morbidity due to more focal coronary stenosis in group II, and freedom from cytomegalovirus infection, but did not find significant differences in the long-term survival between patients who received hearts from donors of up to 63 years of age and from those more than 63 years. The acceptance of donors older than 63 years old for HTx does not worsen the outcome of the recipients. The careful selection of older donors, with close monitoring of the coronary situation after HTx and expanded indications for revascularization of older hearts, could make HTx with older hearts, even in older recipients, a safe option.     

Outcome of pediatric heart transplantation in blood culture positive donors in the United States

Active donor infection at the time of organ procurement poses a potential infection risk and may increase post‐transplant morbidity and mortality in recipients. Our hypothesis was that pediatric heart transplant recipients from blood culture positive donors (BCPD) would have increased morbidity and mortality compared to non‐blood culture positive donors (NBCPD). A retrospective analysis of pediatric heart transplant recipients using the organ procurement and transplant network (OPTN) between 1987 and 2015 was conducted. Recipient as well as donor data were analyzed. Propensity score matching with 1:2 ratios was performed for recipient variables. Post‐transplant morbidity and mortality were compared for recipients of BCPD and NBCPD. Among 9618 heart transplant recipients, 450 (4.7%) were from culture positive donors. Recipients of BCPD had longer duration of listing as Status 1; diagnosis of congenital heart disease or restrictive cardiomyopathy and required support (IV inotropes, Inhaled NO and LVAD) prior to transplant. Post‐transplant survival between the 2 groups was not different. Propensity‐matched recipients had similar length of stay; stroke rate; need for dialysis; pacemaker implantation and treated rejection episodes in the first year post‐transplant. Careful acceptance of BCPD may have the potential to increase availability of donor hearts in the pediatric population.     

Natural leukocyte interferon alfa for the treatment of chronic viral hepatitis in heart transplant recipients

BACKGROUND: A more rapid and aggressive course of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related infection in organ transplant recipients has been described. Interferon alfa is the most accepted drug for treating HBV and HCV chronic infections. However, the use of interferon alfa-N3 has been contraindicated in heart transplant (HTx) recipients because of the hypothesized greater risk of triggering acute cellular rejection. The aim of this clinical pilot study was to evaluate tolerability, safety, and efficacy of natural leukocyte interferon alfa in the treatment of chronic HBV and HCV in HTx recipients. METHODS: Seven HTx recipients were enrolled in the study: two with HBV, four with HCV, and one with combined HBV-HCV chronic infection. The patients had a mean follow-up after heart transplantation of 8.5+/-3 years, before starting interferon alfa-N3 treatment at a dose of 6 MU three times per week, intramuscularly for 12 months. RESULTS: All patients completed the treatment with no major side effects. No unexpected episodes of acute cellular rejection were observed during the treatment. Mean aminotransferase serum levels were significantly lower than before transplantation at 3 (P<0.03), 6 (P<0.02), and 12 (P<0.02) months of treatment and at the 12-month follow-up (P<0.02). A complete and sustained response was achieved in all subjects with HBV-related chronic hepatitis, whereas sustained virologic response was observed in one of four HCV patients. CONCLUSIONS: The preliminary data emerging from our study indicate that natural leukocyte interferon alfa-N3 can be safely administered in HTx recipients with chronic HBV or HCV viral hepatitis. Further studies with larger numbers of patients are needed to assess the efficacy of interferon alfa-N3 on HCV virologic response.     

Factors predicting 10-year survival after heart transplantation.

BACKGROUND: We sought to identify factors predictive of long-term (>10-year) survival in heart transplant (HTx) recipients. METHODS: Four hundred fifteen adult patients underwent HTx at our institution between August 1982 and May 1997. The 158 patients who survived >10 years (Group A) and the 116 patients who died between 2 and 6 years (Group B) of HTx were compared in terms of gender, gender mismatch, ethnicity, age, height, weight, United Network for Organ Sharing status, type of induction therapy (OKT3 or anti-thymocyte globulin), infections (bacterial, viral, fungal and protozoal), cytomegalovirus (CMV) status, CMV mismatch, diabetes mellitus, hypertension and incidence of rejection episodes and transplant coronary artery disease within 2 years of HTx. RESULTS: Group A (135 men, 23 women; mean age 48 +/- 11 years) had significantly fewer post-HTx rejection episodes and viral, bacterial, fungal and total infections than did Group B (95 men, 21 women; mean age 49 +/- 12 years). Group A also had a significantly lower mean donor age, a lower incidence of pre-HTx diabetes, and a lower mean cholesterol level 1 year after HTx. In a multivariate analysis, fewer bacterial infections and rejection episodes after HTx, the absence of pre-HTx diabetes, and lower donor age were associated with longer survival. CONCLUSIONS: Pre-HTx diabetes, donor age and incidences of infection and rejection within 2 years of HTx predict long-term (>10-year) survival. Better control of infection and rejection during the first 2 years after HTx may improve survival.     

Human Herpesvirus 8 (HHV8) Transmission and Related Morbidity in Organ Recipients

The aims of the study were to assess the risk of HHV8 transmission resulting from organ transplantation, and related morbidity in liver, heart and kidney transplant recipients. Donor and recipient serologies were screened between January 1, 2004 and January 1, 2005 using HHV8 indirect immunofluorescence latent assay (latent IFA) and indirect immunofluorescent lytic assay (lytic IFA). Recipients negative for latent IFA with a donor positive for at least one test were sequentially monitored for HHV8 viremia and underwent serological tests over a period of 2 years. The results showed that among 2354 donors, HHV8 seroprevalence was 9.9% (lytic IFA) and 4.4% (latent IFA). A total of 454 organ recipients (281 renal, 116 liver and 57 heart) were monitored over a 2‐year period. Seroconversion was observed in 12 patients (cumulative incidence 28%) whose donor had positive latent IFA and in 36 patients (cumulative incidence 29%) whose donors were positive only for lytic IFA, without differences across types of transplants. Positive HHV8 viremia was detected in only 4 out of 89 liver transplant recipients during follow‐up and not in recipients of other types of transplant. Two liver transplant recipients and one kidney transplant recipient developed KS. In conclusion, although HHV8 transmission is a frequent event after organ transplantation, HHV8‐related morbidity is rather rare but can be life threatening. Donor screening is advisable for monitoring HHV8 seronegative liver transplant recipients.     

High incidence of severe infections in heart transplant recipients receiving tacrolimus

BACKGROUND: Tacrolimus (FK) is being increasingly used as an alternative to cyclosporine (CyA) in heart transplantation (HTx). It is believed to engender slightly more powerful protection against acute rejection. However, the increased immunosuppression could result in an excess of infectious complications. METHODS: Our study compared the incidence of major infections (MInf), defined as life-threatening infectious episodes requiring admission and intravenous (IV) antimicrobial therapy, among a series of HTx recipients treated with either FK (n=30) or CyA (n=84). RESULTS: A total of 21 patients received FK in an elective protocol and 9 patients initially treated with CyA were converted to FK. Tacrolimus was combined with azathioprine and prednisone in 21 cases, and with mycophenolate mofetil and steroids in 8 recipients. After a follow-up between 6 and 37 months, 11 patients (37%) in the FK group developed 13 episodes of MInf, most (85%) occurring during the first posttransplant year. Conversely, CyA patients (n=84), a group with similar characteristics and follow-up, showed a MInf incidence of 12% (P<.05). Among the FK group, the most common site of MInf was pulmonary (69%). A variety of opportunistic agents caused MInf in 54% of cases, whereas the remaining ones were attributed to nosocomial bacteria. There were three deaths (27% of all MInf), all in azathioprine-treated patients with initial FK therapy. CONCLUSIONS: Tacrolimus therapy seems to be associated with an increased incidence of severe infections in HTx recipients. We recommend aggressive diagnostic and therapeutic approaches for patients on FK who develop signs or symptoms of infection in the first year after HTx.     

Extracoporeal Membrane Oxygenation to Rescue Cardiopulmonary Failure After Heart Transplantation: A Single-Center Experience

Extracorporeal membrane oxygenation (ECMO) can provide excellent mechanical circulatory support (MCS). Some case reports use ECMO to rescue heart transplantation (HTx) recipients with posttransplant cardiopulmonary failure. Herein reported a series of use of ECMO to rescue HTx recipients with refractory cardiopulmonary failure have during the posttransplant period. The causes of cardiopulmonary failure were right ventricular failure, primary graft failure, acute rejection, or sepsis. A retrospective review of 366 consecutive HTx recipients revealed 40 cases of cardiopulmonary failure requiring ECMO rescue in the posttransplant period. There were 14 patients diagnosed as right ventricular cardiopulmonary failure; 7 primary graft failure with a stunned donors myocardium, 8 as acute cellular or humoral rejection, and 11 as sepsis with positive blood cultures. ECMO-related variables were evaluated for association with mortality. The HTx recipients included 35 males and 5 females with overall median age of 42.3 years (range, 0.48-65.22). The weaning rate was 72.5% (29/40) and survival, 52.5% (21/40). ECMO provided temporary MCS rescuing some HTx recipients with posttransplant cardiopulmonary failure. None of the patients receiving ECMO support for >4 days survived.     

Small vessel disease after heart transplantation: impact of immunologic and nonimmunologic risk factors*

To determine risk factors for small vessel disease after heart transplantation (HTx), characteristics of donors and organ harvesting were evaluated in 246 HTx patients (205 male, 41 female, mean survival 5.4 years). In right ventricular endomyocardial biopsies (EMB, n = 5421) evidence of microvascular disease [endothelial cell (EC) swelling/vessel wall thickening] was evaluated by light microscopy (hematoxylin and eosin staining, ×200). Mild EC swelling/vessel wall thickening were found in 204 and 213 patients, severe EC swelling/vessel wall thickening were present in 23 and 142 patients respectively. Evidences of mild and severe acute cellular rejection were found in 2064 and 421 EMB respectively. Microvascular disease was positively correlated with mild acute rejection episodes (P < 0.05). EC swelling was more frequent in patients with donors dieing of craniocerebral trauma. No correlations were present to further demographical data. Microvascular alterations after HTx seem to be the result of an immunologic conflict rather than to depend on nonimmunologic factors.     

Blood type incompatible cardiac transplantation in young infants.

OBJECTIVE: Donor organ shortage in pediatric heart transplantation (HTx) is causing mortality rates of 30-50% on the waiting list. Due to immaturity of the immune system of newborns and infants, ABO-incompatible HTx may be an option to increase donor availability. We present our experience with ABO-incompatible HTx. METHODS: Three infants were transplanted ABO-incompatible since 12/2004: (1) hypoplastic left heart complex, (2) restrictive hypertrophic cardiomyopathy, (3) dilative cardiomyopathy. Age at HTx was 7, 5, and 3.5 months. All recipients had blood type O, donors were A, A, and B. Informed consent was given by parents, the ethics committee, and Eurotransplant. RESULTS: Preoperative isohemagglutinin titers were low (Patient 1: 1:4 for anti-A1, A2, B, Patient 2: 1:4, 1:1, 1:4 for anti-A1, A2, B, respectively, and Patient 3: 0 for all, but quick spin 1+ for all). Intraoperatively, plasma was separated from red blood cells and discarded up to six times until antibodies were eliminated. Immunosuppressive induction with ATG was started for 5 days. Basic immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Extubation was performed on days 15, 2, and 1, respectively. After a follow-up of 17, 16, and 12 months all patients are well, ventricular function is excellent without any acute rejection periods; Patient 1 is still on dialysis. Isohemagglutinin titers against donor blood type have disappeared in follow-up. CONCLUSIONS: ABO-incompatible cardiac transplantation shows good short-term results in young infants and seems to be a safe procedure to lower the mortality on the waiting list.     

Heart transplant coronary artery disease in Chinese recipients

BACKGROUND: Transplant coronary artery disease is the principle limiting factor for long-term survival of heart transplantation (HTx) recipients. We reviewed our data to assess the incidence of this disorder among Chinese HTx recipients and to compare it with the results of Western studies. MATERIAL AND METHODS: From July 1988 to May 2002, 182 patients received 184 orthotopic HTx. One hundred sixty-three recipients survived for at least 1 year with available SPECT scans or coronary angiogram studies. The data set included donor characteristics, recipient characteristics, active cytomegalovirus (CMV) infection rate, rejection episodes, immunosuppressants, and human leukocyte antigen (HLA) mismatches. RESULTS: Surgical mortality in our program was 4.3% and the actuarial freedom from coronary artery disease at 1, 3, and 5 years was 99%, 95%, and 92%, respectively. Angiogram results were stratified into coronary artery disease (n = 15) or absence of the disorder (n = 148) groups. Only older donor age showed statistical significance between the groups. Compared with the Western series, the present data show higher actuarial survival rates and freedom from coronary artery disease. There were statistically significant differences in regard to graft ischemia time, proportion of male recipients, ischemic heart disease, rejection episodes during the first year, and incidence of CMV infection. CONCLUSIONS: SPECT scan can detect coronary artery disease before there is significant stenosis of the coronary artery with acceptable survival rates. Chinese HTx recipients show a lower incidence of the disorder, lower rates of ischemia heart disease, lower proportion of male gender, lower incidence of CMV infection, fewer rejection episodes during the first year, and less ischemic time than Western recipients, which maybe the contributing factors to their better survival.     

Outcomes of Heart Transplantation for Cardiac Amyloidosis: Subanalysis of the Spanish Registry for Heart Transplantation

Amyloidosis (Am), a systemic disease, has poor prognosis because of organ damage produced by protein deposition in the extracellular space. Although heart transplantation (HTx) is possible, donor availability concerns and high mortality make this approach controversial. The Spanish Registry for Heart Transplantation includes 25 Am patients (54 ± 9 years): 13 with AL type, 2 with AA and 10 with TTR mutation. Fifteen patients (60%) died during follow-up (4.9 ± 1.3 years): 9 AL-Am patients, both AA-Am patients and 4 with TTR-Am. HTx survival for Am patients was similar to patients without Am at 1 month but significantly worse at 5 years: 46% versus 78% (p < 0.02). Of 10 AL-Am patients undergoing successful HTx, 4 died of systemic Am. Stem cell transplantation was performed in 3 (1 died of acute rejection). Five of 10 patients with TTR-Am underwent liver transplant; 4 remained alive at the last follow-up. Findings include poor outcome for AL-Am patients despite HTx and better survival for TTR-Am patients if HTx is associated with liver transplantation. Given the shortage of donors and poor outcome for Am patients, we would recommend that HTx be reserved for patients without or with mild systemic Am and be supplemented by additional therapies as indicated.     

HBV and HCV infections in heart transplant recipients.

BACKGROUND: Heart transplant (HTx) recipients risk acquiring hepatotropic viral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of these infections on post-HTx survival remains unclear. The aim of the present study was to define the prevalence, clinical features, and natural history of HBV and HCV infections in a cohort of HTx recipients. METHODS: We retrospectively studied 360 consecutive patients who had undergone HTx. Clinical picture, hepatic injury indexes, and HBV/HCV viral serology were followed post-transplant. RESULTS: During follow-up (average, 8 +/- 3.1 years), 49 (16.5%) of the HTx recipients tested positive for at least 1 of the 2 viruses (3.1% HBV, 12% HCV, 0.5% concomitant infection). The prevalence of HCV infection in heart transplant recipients transplanted before and after 1990 was 28% and 4.2%, respectively, the latter being markedly lower (p < 0.001) than in earlier series of HTx recipients and much lower than expected in the age- and sex-matched general population. All HBV-positive and 58% of HCV-positive recipients developed chronic liver disease. Sixteen percent of patients developed cirrhosis during follow-up, and 8% died of end-stage liver disease. CONCLUSIONS: The prevalence of HBV and HCV in a large population of HTx recipients is not very different from that reported in the general population. Active viral replication of HBV and an aggressive natural history of both infections are seen in HTx recipients, however. The low prevalence of HBV- and HCV-related infection in recent series probably reflects current viral screening and vaccination policies.     

Heart transplantation in the patient under ventricular assist complicated with device-related infection

Ventricular assist devices (VAD) have benefited patients with end-stage heart failure as a bridge to heart transplantation (HTx). We present our experience of HTx in the presence of device-related infection (DRI) including driveline exit site with pocket infections. From May 1996 to April 2003, mechanical circulatory support with the HeartMate VAD was performed in eight patients, and with the Thoratec VAD in seven patients. Although 151 patients underwent HTx during that period, only 8 of the 15 patients had suitable donors and underwent orthotopic HTx. Six of the eight patients developed DRI. Their ages ranged from 18 to 59 years (mean = 36 +/- 14 years). The duration of VAD support ranged from 8 to 287 days (mean = 125 +/- 117 days). The general condition and cardiac function improved gradually under VAD support. At the time of HTx, all six male patients were suffering from DRI. The causative microorganisms were Acinetobacter baumannii (n = 3) methicillin-resistant Staphylococcus aureus (n = 2), and Enterococcus faecium (n = 1). All patients underwent successful HTx, and were discharged in good condition. It is concluded that under the coverage of appropriate antibiotics, HTx can be successfully performed for the patients for VAD support with DRI. It is important to prevent the spread of infection during HTx. Adequate debridement and drainage of the infected materials prevents postoperative wound infections.     

Effect of posttraumatic donor's disseminated intravascular coagulation in intrathoracic organ donation and transplantation

INTRODUCTION: Our aim was to evaluate the influence on yield and function of intrathoracic organs from donors after severe cranial trauma complicated by disseminated intravascular coagulation (DIC). MATERIALS AND METHODS: This retrospective observational study in a patient cohort with severe cranial trauma reading to brain death compared the number of harvested thoracic organs among individuals with versus without previous DIC. We examined exclusions for organ donation and their probable relationship to DIC. We also analyzed blood components transfused to normalize coagulation parameters. The organ recipients were followed for 1 month to detect acute graft failure. RESULTS: Among 147 organ donors, 37 were brain dead after suffering severe cranial trauma and 13 met DIC criteria upon admission. We did not observe demographic differences among donors, although there was a trend for DIC donors to be younger (32 +/- 10 vs 40 +/- 21 years old; P = .11). Twenty-eight donors (12 with DIC and 16 without) and 29 donors (13 with DIC and 16 without) met age and medical criteria for potential heart or lung donation, respectively. Donation exclusion was related to trauma instead of DIC itself. We did not find any difference among the number of cardiac and lung organs harvested from organ donors with DIC (67% and 31%, respectively) or without DIC (75% and 44%, respectively). All DIC donors had clinical bleeding and received multiple units of blood products. Organs were harvested 37 +/- 23 (13 to 80) hours after admission. All patients had normalized coagulation parameters at surgery. In the postoperative evolution, none of the cardiac or lung recipients from DIC donors met primary graft failure criteria. CONCLUSIONS: We concluded that hearts and lungs from donors with previous DIC were suitable for transplant recipients.     

Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986

We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV-1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P less than 0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1.     

Preferential Depletion of Blood Myeloid Dendritic Cells During Acute Cardiac Allograft Rejection Under Controlled Immunosuppression

Allo-Ag presentation to Ag-specific T-lymphocytes by donor or recipient dendritic cells (DCs) induces acute rejection (AR) after solid organ transplantation. It is postulated that myeloid (mDC) and plasmacytoid (pDC) subsets circulate differentially between bone marrow, heart and lymphoid tissues after cardiac transplantation (HTx). We investigated peripheral blood DC subset distribution, maturation and lymphoid homing properties in relation to endomyocardial biopsy (EMB) rejection grade after clinical HTx. Twenty-one HTx recipients under standard immunosuppression were studied in a 9-month follow-up. mDC and pDC numbers were analyzed by flow cytometry in fresh venous whole blood samples collected during the EMB procedures and before histological diagnosis of AR. Subsets were further characterized for maturation marker CD83 and lymphoid homing chemokine receptor CCR7. Although numbers of both DC subsets remained low for the whole post-HTx period, we observed a negative association of mDCs with rejection grade. Repeated measurements analysis revealed that only mDCs decreased during AR episodes. Rejectors had lower mDC numbers after a 3-month follow-up compared to nonrejectors. Furthermore, patients during AR exhibited low proportions of mDCs positive for CD83 or CCR7. These findings suggest peripheral blood mDC depletion in association with selective lymphoid homing of this subset during AR after clinical HTx.     

Disease recurrence and rejection following liver transplantation for autoimmune chronic active liver disease.

Autoimmune chronic active liver disease (ACALD), a major indication for liver transplantation, is associated strongly with antigenic determinants HLA-B8 and DR3. A retrospective analysis of 43 patients who underwent OLTx for putative ACALD and who, as well as their tissue organ donors, were typed, was performed. Disease recurrence and graft rejection episodes were determined by chart review and histopathological review of all material available. Disease recurrence was histologically documented in 11 (25.6%) of these 43 cases. Graft rejection episodes occurred in 24 (55.8%). All recurrences were in recipients of HLA-DR3-negative grafts. Nine of the recurrences were in HLA-DR3-positive recipients (odds ratio: 6.14, P less than 0.03). Two of 11 cases of disease recurrence were in recipients who were HLA-DR3-negative. Nine of these 11 had received HLA-DR3-negative grafts. Rejection occurred in 13 HLA-B8-positive recipients, 12 of whom received HLA-B8-negative grafts. Eleven HLA-B8-negative recipients experienced at least one rejection episode and 9 of these had received HLA-B8-negative grafts. Based upon these data we conclude: 1) that recurrence of putative ACALD is more likely to occur in HLA-DR3-positive recipients of HLA-DR3-negative grafts; (2) that recurrences were not seen in recipients of HLA-DR3-positive grafts; (3) that HLA-B8 status does not affect disease recurrence; and (4) that neither the HLA-B8 nor the DR3 status of the graft or recipient has an effect on the observed frequency of rejection.     

Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries.

BACKGROUND: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. METHODS: Patients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). RESULTS: Group A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142+/-34 vs 195+/-59, p<0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82+/- 0.33) and a restoration to normal values thereafter (group B: 2.52+/- 0.53 vs NL: 2.62+/-0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. CONCLUSION: This study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.