OKT3 and viral disease in pediatric liver transplant recipients

Seventy-four consecutive pediatric liver transplant recipients were reviewed to assess the effect of the monoclonal anti-T-lymphocyte antibody OKT3 on subsequent viral infection (9 patients were excluded due to postoperative demise during the 1st week). Twenty-two patients received OKT3 in addition to standard cyclosporine-prednisone immunosuppression for either steroid-resistant acute rejection (18) or to facilitate reduction of cyclosporine due to severe renal impairment (4). Invasive infections were diagnosed by histology or culture in tissue biopsies or bronchoalveolar lavage specimens. The overall incidence of viral infection was 58%, half of which was due to cytomegalovirus (CMV). Invasive viral disease was associated with increased mortality (37% vs. 3% p = 0.001). Viral-related deaths were due to CMV (5), disseminated adenovirus (3), disseminated enterovirus (1) and respiratory syncytial viral pneumonia (1). The use of OKT3 was associated with increased viral disease (59% vs. 33% p=0.04) and invasive primary CMV disease (58% vs. 19% p=0.04). Trends were observed toward increased overall viral infection (73% vs. 51 % p=0.08), primary CMV infection (58% vs. 25% p=0.08) and overall mortality (27% vs. 9% p =0.08) following OKT3 therapy. We conclude that pediatric liver transplant recipients who require OKT3 therapy may be at increased risk for invasive viral disease and especially invasive primary CMV disease.     

Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy

BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.     

Infections in cardiac transplant recipients: clinical and microbiological characteristics and consequences

INTRODUCTION: Infections are one of the main complications that cause morbidity and mortality in cardiac transplant recipients. We sought to establish the incidence of infections, identify the predisposing factors and determine their consequences. PATIENTS: A prospective study of 30 patients who received cardiac transplantations in our hospital from July 2003 to May 2005. RESULTS: Of the 30 transplant recipients, 93.3% were men (average age, 48 years); the average age of the women was 53 years. The incidence of infection was 70%: 21 episodes of infection. The main clinical symptoms were bacteriemia (28%), pneumonia (19%), and surgical wound infections (14%). The etiology of the infection, as established in 12 cases (57%), was bacterial (66%), viral (25%), or fungal (9%). The most common microorganisms were cytomegalovirus and coagulase-negative staphylococcus. None of the donors had a history of infection. There was a higher frequency of serious complications, such as renal failure (12.9%), respiratory insufficiency (9.6%), and multiorgan failure (9.6%) among patients with versus without infections (P < .05). The 1-year survival rate of patients with infections was similar to that of patients with no infections (83% vs 88%, P = NS). CONCLUSIONS: The incidence of infections was 70%. Bacteremia, pneumonia, and surgical wound infections occurred most frequently. Cytomegalovirus and coagulase-negative staphylococcus were the most frequent microorganisms. Patients with infections had the most serious complications, but their survival rate was similar to that of patients free of this complication.     

Influenza Virus Infection in Adult Solid Organ Transplant Recipients

BACKGROUND: Solid organ transplant (SOT) recipients have been reported to be more susceptible to influenza virus. However, little is known about the clinical epidemiology and the implications of influenza viral infection among SOT recipients. METHODS: Cohort study of influenza viral infection in SOT recipients at the University of Pittsburgh Medical Center. RESULTS: Between November 1990 and April 2000, 30 cases of influenza were diagnosed in SOT recipients at our center, including influenza A (n = 22) and influenza B (n = 8). These included recipients of lung (n = 19), liver (n = 5) and kidney (n = 6) transplants. The incidence of influenza viral infection was 41.8 cases/1,000 person years (PYs), 2.8 cases/1000 PYs and 4.3 cases/ 1,000 PYs among lung, liver and renal transplant patients, respectively (p <0.0001). Symptoms were reported in all patients and included malaise, myalgia/ arthralgia, fever, cough, and shortness of breath. Secondary bacterial pneumonia occurred in five patients (17%). Other complications were seen in three SOT recipients (2 liver and 1 kidney) and included: myocarditis, myositis, and bronchiolitis obliterans. Biopsy of the transplanted organ was performed in 21 SOT recipients (18 lung, 1 liver and 2 kidney) at the time of influenza viral infection. Overall, 62% (13/21) showed variable degrees of acute allograft rejection, and included 61% (11/18) of lung, and 100% (2/2) of kidney transplant recipients. CONCLUSIONS: Influenza infection is associated with significant morbidity in different groups of SOT recipients. Studies are needed to determine if yearly chemoprophylaxis with antiviral drugs might benefit this patient population.     

Infection frequency and profile in different age groups of kidney transplant recipients

BACKGROUND: Older transplant recipients have been shown to be at greater risk for infectious death than younger adults, but no study to date has looked at relative risk of infection and infection profile differences for children versus adults, which may be very different from one another. METHODS: Data from primary Medicare renal transplant recipients between 1991 and 1998 (n=64,751), as reported in the United States Renal Data System (USRDS), were analyzed for Medicare claims (both inpatient and outpatient) for infection and type of infection in the first year posttransplant. Cox regression was used to model adjusted hazard ratios (AHR) for infection. RESULTS: Total infections among renal transplant recipients increased significantly in more recent years. Patients transplanted in or after 1995 had a significantly higher adjusted risk for infection compared to those transplanted earlier (AHR 1.34, 95% CI=1.29-1.39). Older adults > or = 51 years of age had the highest percentage of experiencing infection, as compared to adults between 18-50 years and children < or = 17 years (P<0.001). Children were at highest risk of viral infection prior to 1995 but at lowest risk of viral infection after 1995, whereas elderly adults were at highest risk of bacterial infection throughout the study. Children experienced more claims for viral infections, whereas older transplant recipients experienced more claims for bacterial infections. CONCLUSIONS: The two extremes of transplant recipient age display very different risks for infection claim frequency and profile.     

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.

BACKGROUND: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. METHODS: English-language articles identified by a MEDLINE search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. RESULTS: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality. CONCLUSIONS: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart-lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.     

Preoperative risk factor assessment in liver transplantation.

BACKGROUND. Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS. We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS. The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS. These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.     

Increased incidence of gastrointestinal surgical complications in renal transplant recipients with polycystic kidney disease

BACKGROUND: We had the impression that, although our renal transplant recipients with polycystic kidney disease (PKD) had excellent long-term renal graft function, they had an increased incidence of postoperative gastrointestinal (GI) complications. METHODS: Over a 10-year period (1987 through 1996), 1467 renal transplants were performed in 1417 patients; 145 of these transplants involved PKD recipients. In the PKD group, 18 patients (12.4%) developed a posttransplant complication necessitating GI surgery (PKD-GI), an incidence twice that in the non-PKD recipients (73 patients or 6.2%, non-PKD-GI). RESULTS: PKD and non-PKD recipients displayed no significant difference in mortality. The PKD patients had better long-term renal graft survival than the non-PKD patients (P=0.08). There was no difference in mortality (P>0.6) or renal graft survival (P>0.6) between the PKD-GI and PKD-non-GI groups. The PKD-GI group had no increased mortality over the non-PKD-GI patients (P>0.6), despite a higher incidence of GI surgical complications in the PKD group versus the non-PKD group (overall: 12.4 vs. 6.2%, P<0.01; within 90 days of transplant: 7.6 vs. 3.3%, P<0.02) and a greater propensity for small and large bowel complications (overall: 9.0 vs. 2.6%; P< 0.001; less than 90 days: 6.9 vs. 2.0%, P<0.002). The PKD-GI recipients tended toward less long-term graft loss than their non-PKD-GI counterparts (11.1 vs. 27.4%; P=.22). The PKD-GI recipients suffered no acute rejection episodes within 90 days after their GI operation versus 11 of 73 non-PKD-GI recipients (O vs. 15.1%; P=0.075). CONCLUSIONS: PKD recipients of renal grafts should be watched closely early after transplant because of their increased risk of GI complications. These complications resulted in no increase in mortality or graft loss compared to non-PKD recipients with GI complications despite the PKD group's higher incidence of bowel perforation and increased age at time of transplant.     

Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients

BACKGROUND: Invasive fungal infection has a major impact on the morbidity and mortality of liver transplant recipients. Human herpesvirus (HHV)-6 infection after transplantation is associated with an immunosuppressive state and the development of cytomegalovirus disease. Because cytomegalovirus infection is a risk factor for invasive fungal infection after transplantation, we have examined whether HHV-6 and fungal infection are associated after transplantation. METHODS: Pretransplantation sera from 247 consecutive liver transplant recipients were analyzed for IgG to HHV-6. Thirty-three (13%) HHV-6-seronegative recipients were identified. Six of 33 (18%) seronegative recipients experienced fungal infection as compared with 15 of 214 (7%) seropositive recipients (P=0.034). RESULTS: In a univariate analysis of risk factors for fungal infection, pretransplantation seronegativity to HHV-6 (P=0.034), intraoperative cryoprecipitate requirements greater than the 75th percentile (P=0.035), reoperation (P=0.005), biliary stricturing postoperatively (P=0.046), and gastrointestinal or vascular complications postoperatively (P=0.030) were identified as significant risk factors. Moreover, in pairwise multivariate analysis, pretransplantation HHV-6 seronegativity remained a significant variable even in the presence of each of the other variables. CONCLUSIONS: These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation.     

Mucocutaneous lesions in transplant recipient in a tropical country

Dermatological manifestations are common in renal transplant patients, but differ markedly with ethnic group and geographical location. We studied mucocutaneous lesions in 54 renal allograft recipients (related donors = 30; unrelated donors = 24) living in tropical atmospheres. Their gender was 50 males, and 4 females ranging in age between 15 and 63 years (mean = 37.84 years). The mean duration of follow-up was 124 months (range = 4 to 173 months). All patients received kidneys from living donors and were kept on immunosupression with mean daily doses of prednisolone, azathioprine, and cyclosporine of 10.2 mg, 68.6 mg, and 252 mg, respectively. The mean trough concentration of cyclosporine was 185 ng/mL. The mucocutaneous lesions were divided into four groups: drug-induced (n = 24, 44.4%), fungal (n = 18, 33.3%), viral (n = 9, 16.6%), and bacterial (n = 10, 18.5%). Cushingoid features, gum hypertrophy, and hypertrichosis were seen in 7 (12.9%) patients. Steroid acne was seen in three cases. Pityriasis versicolor was the most common (20.3%) fungal infection of the skin. In addition, Tinea unguium and mucocutaneous candidiasis were noted in four and three cases respectively. Herpes virus infection (Herpes zoster 5; Herpes simplex 2) was noted in 7 (12.9%) cases. Chicken pox at 5 years posttransplant and cutaneous vasculitis associated with cytomegalovirus disease at 6 months posttransplant were seen in one case each. We have not seen warts in our patients. Pyogenic bacterial infection of skin in the form of abscess (n = 6), cellulitis (n = 3), and pyoderma (n = 1) were observed in 10 (18.5%) patients. Thus, drug-induced mucocutaneous side effects and skin fungal infections are the most common dermatological manifestations among renal transplant recipients living in a tropical country.     

Mannose‐Binding Lectin–Deficient Donors Increase the Risk of Bacterial Infection and Bacterial Infection–Related Mortality After Liver Transplantation

Mannose‐binding lectin (MBL) is synthesized by the liver and binds to microbes. MBL2 gene polymorphisms produce intermediate/low/null or normal MBL serum levels (MBL‐deficient or MBL‐sufficient phenotypes, respectively). We aimed to evaluate the incidence and severity of infection, rejection, and survival within 1 year after liver transplantation (LT) according to donor and recipient MBL2 gene polymorphisms. A repeated‐event analysis for infection episodes (negative binomial regression, Andersen–Gill model) was performed in 240 LTs. Four hundred twenty‐eight infectious episodes (310 bacterial, 15 fungal, 65 cytomegalovirus [CMV]‐related, and 38 viral non–CMV‐related episodes) and 48 rejection episodes were recorded. The main bacterial infections were urinary (n = 82, 26%) and pneumonia (n = 69, 22%). LT recipients of MBL‐deficient livers had a higher risk of bacterial infection (incidence rate ratio [IRR] 1.48 [95% confidence interval 1.04–2.09], p = 0.028), pneumonia (IRR 2.4 [95% confidence interval 1.33–4.33], p = 0.013), and septic shock (IRR 5.62 [95% confidence interval 1.92–16.4], p = 0.002) compared with recipients of MBL‐deficient livers. The 1‐year bacterial infection–related mortality was higher in recipients of MBL‐deficient versus MBL‐sufficient livers (65.8% vs. 56.1%, respectively; p = 0.0097). The incidence of rejection, viral, or fungal infection was similar in both groups. Recipient MBL2 genotype did not significantly increase the risk of bacterial infection. LT recipients of MBL‐deficient livers have a higher risk of bacterial infection, pneumonia, septic shock, and 1‐year bacterial infection–related mortality after LT.     

Spectrum of severe infections in an Asian renal transplant population

Infections in renal transplant recipients (RTX) account for 26% of hospitalization days annually and 40% of overall mortalities. A retrospective study of infections requiring hospitalization occurring among 725 Asian RTX in 2002 was performed. RESULTS: Serious infections requiring at least one hospitalization occurred in 9.2% of RTX (n = 67). Multiple pathogens affected 28.4% of patients, resulting in 118 infectious episodes during 93 hospitalizations. Mean age of affected patients was 48 years and female to male ratio was 2:1. Forty-one (61.2%) had impaired renal function (serum creatinine >141 mumol/L). Mean duration of hospitalization per patient was 17 days and the in-patient mortality rate was 17.9% eighty-one (87%) hospitalizations were for late infections (>6 months posttransplant). Cyclosporine (CsA) with prednisolone with or without azathioprine was the immunosuppressant in 62.7% (n = 42) of RTX but proportionally, infections were more frequent among RTX on other more potent immunosuppressants (n = 21; 7.4% CsA-based vs. 19.3%, potent, P < .05). Bacterial, viral, fungal, and Pneumocystis carinii infections comprised 64.4%, 20.3%, 5.9%, and 4.2% respectively. Urinary tract infection, pneumonia, and bacterial septicemia (35.52%, 31.6%, and 11.8%, respectively) were the major presentations. E. coli, cytomegalovirus (CMV), and Candida were the most common pathogens. Notably, 13 out of 18 (72.2%) viral CMV infections were co- infections, occurring together with bacterial infections. CONCLUSIONS: Late infections with the use of potent immunosuppressives and concurrent CMV reactivation are a major cause of morbidity. Longer antibacterial prophylaxis and closer monitoring for CMV infections may help reduce morbidity.     

Infectious complications after OKT3 induction in liver transplantation

The present study examines the incidence, risk factors, bacteriology, and mortality of infectious episodes and the role of antimicrobial prophylactic regimens after OKT3 induction in liver transplantation. Infections occurring in the first 6 months were evaluated according to the Centers for Disease Control criteria in 102 transplant recipients. Patients were administered OKT3 for 5 to 10 days, beginning intraoperatively, azathioprine, low-dose prednisone, and delayed introduction of cyclosporine. There were 140 major and 30 minor infections for an incidence of 1.7 infections per patient. Twenty-seven patients (26%) had no infectious episodes during the 6 months of follow- up. Bacterial and fungal infections peaked during the first month posttransplantation, whereas viral infections peaked during the second month. Infection-related mortality was 10%. One-year survival rate of patients who suffered a major infection was less than those who were infection free, but the difference was not statistically significant (79% vs. 89%; P = .61). There was a significantly higher incidence of enterococcal infections under cefotetan prophylaxis than under ampicillin-sulbactam (.375 vs. 11 infections per patient; P = .0017). There were 14 episodes of cytomegalovirus disease (14%) but no cytomegalovirus-related mortality or graft loss, and all cases responded to ganciclovir treatment. Bivariate and multivariate analyses identified only retransplantation as a risk factor for infection. In conclusion, OKT3 induction after liver transplantation is associated with a manageable incidence of bacterial, viral, or fungal infections. This is caused by, at least in part, improved anti-infective prophylaxis. (Liver Transpl Surg 1997 Nov;3(6):563-70)     

Opportunistic upper gastrointestinal infection in transplant recipients

Opportunistic infection of the upper gastrointestinal tract by cytomegalovirus (CMV) or invasive fungal infection was studied in 219 consecutive kidney and kidney/pancreas transplant recipients with regard to incidence, presentation, and clinical outcome. Prompt upper endoscopy was done in all patients with these symptoms: dyspepsia, dysphagia, or bleeding. Multiple biopsies were obtained for fungal culture, CMV culture, CMV assay, and histologic examination for fungal invasion.Between April 1991 and July 1993, 57/219 (26%) transplant patients developed upper gastrointestinal symptoms. At endoscopy, gross mucosal abnormality was evident in 48/57 (84%). Opportunistic infection was found in 21/48 (44%); however, CMV infection was also detected in 2/9 (22%) who had a normal study. Overall, CMV was present in 15/57 (26%) and invasive fungal infection in 8/57 (14%). All 23 infections were successfully eradicated. Opportunistic infection occurred in 12/31 (39%) with dyspepsia, 9/14 (64%) with dysphagia, and 2/12 (17%) with bleeding. Graft loss occurred in 5/23 (22%) with opportunistic infection vs 23/196 (12%) other recipients.Upper gastrointestinal symptoms are indicative of serious opportunistic infection in a significant number of transplant recipients. As opportunistic infection may jeopardize allograft function, all patients with upper gastrointestinal tract symptoms require prompt endoscopy and biopsy to effect appropriate therapy. Random biopsy is also recommended in the face of a normal endoscopic examination.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Nashville, Tennessee, USA, 18–19 April 1994     

Risk Factors for Rejection and Infection in Pediatric Liver Transplantation

Rejection and infection are important adverse events after pediatric liver transplantation, not previously subject to concurrent risk analysis. Of 2291 children (<18 years), rejection occurred at least once in 46%, serious bacterial/fungal or viral infections in 52%. Infection caused more deaths than rejection (5.5% vs. 0.6% of patients, p < 0.001). Early rejection (<6 month) did not contribute to mortality or graft failure. Recurrent/chronic rejection was a risk in graft failure, but led to retransplant in only 1.6% of first grafts. Multivariate predictors of bacterial/fungal infection included recipient age (highest in infants), race, donor organ variants, bilirubin, anhepatic time, cyclosporin (vs. tacrolimus) and era of transplant (before 2002 vs. after 2002); serious viral infection predictors included donor organ variants, rejection, Epstein-Barr Virus (EBV) naivety and era; for rejection, predictors included age (lowest in infants), primary diagnosis, donor-recipient blood type mismatch, the use of cyclosporin (vs. tacrolimus), no induction and era. In pediatric liver transplantation, infection risk far exceeds that of rejection, which causes limited harm to the patient or graft, particularly in infants. Aggressive infection control, attention to modifiable factors such as pretransplant nutrition and donor organ options and rigorous age-specific review of the risk/benefit of choice and intensity of immunosuppressive regimes is warranted.     

Complications by age in primary pediatric renal transplant recipients

  We asked whether pediatric renal transplant recipients, subgrouped by age, differed in the percentage and number of hospital readmissions and in the incidence of infectious complications post transplant. Between 1 August 1985 and 31 October 1993, a total of 164 patients <18 years of age underwent primary transplants, with cyclosporine-based immunosuppression, at the University of Minnesota. The percentage of readmissions (P = NS), the mean number of readmissions (P = NS), and the length of hospital stay during readmission (P = NS) did not differ significantly among age groups. The overall incidence of acute rejection was greater in those ≥2 years than those <2 years (P = 0.002), and in living donor recipients ≥2 years versus those <2 years (P = 0.02). The incidence of bacterial infection (<2 years, 87%; 2 – 5 years, 72%; 6 – 12 years, 51%; 13 – 17 years, 40%) was greater in younger recipients (P = 0.0001). The most common bacterial infection in recipients ≤5 years was Clostridium difficile-associated diarrhea; in those >5 years, urinary tract infection. The overall incidence of viral infection did not differ among groups (P = NS). The most common viral infection in recipients ≤5 years was varicella and those >5 years, cytomegalovirus infection. Risk factors for infection in the first 6 months post transplant included age <2 years and Solu-Medrol treatment for acute rejection. In conclusion, young recipients <2 years of age at the time of transplant are at a higher risk for bacterial infection post transplant. Received May 1, 1996; received in revised form and accepted December 16, 1996     

Hepatocellular carcinoma in renal transplant patients

INTRODUCTION: Chronic liver diseases, especially those related to hepatitis B (HBV) and C viruses (HCV), are a common problem in renal transplant patients. Hepatocellular carcinoma (HCC) is a complication of chronic liver diseases, incidence in the renal transplant cohort is higher than in the general population (1.4% to 4% vs 0.005% to 0.015%). METHODS: We retrospectively evaluated the incidence of HCC, its clinical presentation, the treatments, and the relation to chronic viral hepatitis among the population transplanted at our center between January 1980 and December 1998 and followed to August 2003. RESULTS: During the study period, six recipients among 534 renal transplants displayed HCC (incidence 1.12% of the entire population and 2.29% of patients with chronic viral hepatitis). Among the cohort five were men, and all had chronic viral hepatitis: three HBV, one HCV, and 2, a coinfection. HCC was diagnosed 124.1 (range 45 to 244) months after transplantation. All patients presented with abnormal liver function tests and tumors larger than 5 cm. Four had more than three tumors and three had an alpha-fetoprotein level higher than 400 IU/mL. Three patients received no treatment (survivals 1, 1, and 4 months); two patients, chemoembolization (survival 6 and 12 months); and one, surgical ethanol injections (survival 4 months). The overall survival was 4.5 months. CONCLUSION: HCC in renal transplant recipients is a common complication among patients with chronic viral hepatitis. The outcome was poor because HCC was detected at an advanced stage. Screening strategies for early diagnosis must be prospectively evaluated.     

Risk Factors for Hospitalization for Bacterial or Viral Infection in Renal Transplant Recipients—An Analysis of USRDS Data

We previously showed that children are more likely to develop viral infections post-kidney transplant while adults are more likely to develop bacterial infections. In this study we determined the overall risk factors for hospitalization with either a bacterial (HBI) or a viral infection (HVI). We analyzed data from 28 924 United States Renal Data System (USRDS) Medicare primary renal transplant recipients from January 1996 to July 2000, for adjusted hazard ratio (AHR) for HBI or HVI in the first 3 years posttransplant.For HVI, significantly higher AHR was seen with (a) recipient age <18 years (AHR 1.57, 95% CI = 1.02, 2.42), (b) donor CMV positive (AHR 1.72, 95% CI = 1.34, 2.19). For HBI, significantly higher AHR was seen with (i) delayed graft function (AHR 1.28, 95% CI = 1.076, 1.518), (ii) primary renal diagnosis chronic pyelonephritis (AHR 1.71, 95% CI = 1.18, 2.49); (iii) associated pretransplant diabetes (AHR 1.80, 95% CI = 1.53, 2.12); (iv) female gender AHR 1.63, 95% CI = 1.41, 1.88). Lower AHR for HVI was seen in CMV-positive recipients and for HBI with more recent year of transplant. Other covariates did not impact significantly in either HVI or HBI.     

The influence of mycophenolate mofetil versus azathioprine and mycophenolic acid pharmacokinetics on the incidence of acute rejection and infectious complications after renal transplantation

PURPOSE: The present retrospective study investigated the influence of mycophenolate mofetil (MMF) instead of azathioprine (AZA) as part of tacrolimus-based immunosuppression. Mycophenolic acid (MPA) pharmacokinetic (PK) parameters were used for associations with the incidence of acute rejection (AR) episodes and infectious complications after renal transplantation. METHODS: The 66 consecutive renal transplant recipients reported herein excluded ABO-incompatible transplants or cytomegalovirus (CMV)-seronegative recipients. The immunosuppressive regimen consisted of tacrolimus, steroids, and AZA 1-2 mg/kg/d in 22 patients (between February 1998 and December 2000) or MMF 2 g/d in 44 patients (since January 2001). CMV infection was defined as positive CMV-antigenemia. MPA PK was studied on day 28 after transplantation in 21 recipients. RESULTS: AR occurred in 13.6% of patients in the MMF group compared with 18.2% in the AZA group. The viral infection (CMV, varicella zoster virus, adenovirus hemorrhagic cystitis, and malignancy related to Epstein-Barr [EB] virus) rate was 22.7% in the MMF group and 0% in the AZA group (P = .015). There were no bacterial or fungal infections observed in the 2 groups. MMF dose per body weight was significantly lower among patients with AR than those without AR (25.1 vs 35.6 mg/kg; P = .026). There were no differences in MPA PK parameters between patients with and without viral infections. CONCLUSIONS: Patients treated with MMF required less treatment for AR, however, there were no significant differences. MMF dose per body weight may play an important role in the occurrence of AR. Although virus infections occurred in recipients treated with MMF, MPA PK did not influence the infectious complications after renal transplantation.     

Chronic viral hepatitis in renal transplant recipients with allografts functioning for more than 20 years

BACKGROUND: The impact of infection with hepatotropic viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]) on morbidity and mortality, and allograft function in renal transplant recipients with allografts functioning for >20 years is not known. METHODS AND RESULTS: Seventy-nine of 511 renal transplants performed at the Cleveland Clinic Foundation from January 1963 to January 1978 are known to have functioned for at least 20 years (level 5A). Fifty-four of these patients had hepatitis testing updated after their 19th year of transplantation. Fifteen patients had evidence of ongoing viral infection: persistent hepatitis B surface antigen in three (6%), HCV antibody (enzyme-linked immunosorbent assay II supplemented by recombinant immunoblot assay) in 11 (20%), and both viruses in one (2%). Of the 10 surviving patients, 8 were tested further for viral replication. HCV RNA (polymerase chain reaction; Amplicore) was positive in 6/7 (86%), and HBV DNA (hybridization) was positive in 1/2 (50%). An elevated alanine aminotransferase (>35 U/L) was present in all hepatitis patients, alpha-fetoprotein >10 ng/ml in 2/8 (25%), and cryoglobulins >50 microg/ml in 3/6 (50%) infected with HCV. No hepatocellular carcinoma was detected by hepatic ultrasound. In patients with chronic viral hepatitis, probable cirrhosis developed in 20% (3/15) compared to one patient in the group without hepatitis, but there was no mortality from liver failure in either group. Diabetes mellitus was significantly more common in those with than without hepatitis (11/15 vs. 10/39; P=0.002), but severe infection was not (9/15 vs. 15/39). Five hepatitis patients (33%) have died of non-hepatic causes (one from meningitis, one from unknown cause, and three from coronary heart disease [CHD] vs. only two individuals without hepatitis [5%]; P= 0.014). Although the more frequent occurrence of CHD among those with hepatitis was not significant (7/15 vs. 8/39; P=0.09), CHD as a cause of death in those with HCV was significantly increased (P=0.03). CONCLUSIONS: Twenty-year renal transplant recipients infected with hepatotropic viruses (HBV and HCV) have a high rate of active viral replication (88%), a greater frequency of diabetes (P=0.01), and a higher overall mortality (P=0.014).