Safety and efficacy of isoniazid chemoprophylaxis administered during liver transplant candidacy for the prevention of posttransplant tuberculosis

BACKGROUND: Optimal timing of initiation of isoniazid chemoprophylaxis in liver transplant recipients who test positive on the tuberculin skin test has not been defined. We sought to determine whether isoniazid prophylaxis administered during liver transplant candidacy was safe and effective for the prevention of posttransplantation tuberculosis. METHODS: During a 9-year period, 18 liver transplant candidates with tuberculin skin test greater than 5 mm or recent conversion to positive tuberculin skin test were identified and received isoniazid chemoprophylaxis for 12 months. For each case, a control matched with the patient for underlying liver disease and age (within 5 years of the case) was included. Liver function tests were assessed monthly. The median follow-up was 55 months and ranged up to 107 months for the cases. RESULTS: At baseline, the cases had a total bilirubin of 2.2 mg/dL, alanine aminotransferase of 106 IU/L, prothrombin time of 14.2 sec, and serum albumin of 2.9 gm/dL (mean values). Hepatic function tests did not differ significantly for the cases at 3, 6, 9, and 12 months when compared with those at baseline or between the cases and controls at each of the above time points. Discontinuation of prophylaxis was not required in any of the patients. The outcome (proportion of patients who underwent transplantation or were dead or alive at the last follow-up) and survival time for the cases did not differ significantly from those of the controls (P >0.20). CONCLUSION: In liver transplant candidates at risk for infection after transplantation, isoniazid chemoprophylaxis used during candidacy was well tolerated and did not adversely effect hepatic function or outcome as compared with the control patients.     

Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) with isoniazid is recommended for transplant recipients with positive tuberculin skin test (TST). However, TST could be an imperfect identifier of LTBI in this population. In addition, the risk of isoniazid hepatotoxicity could be high in liver transplant recipients (LTR). A retrospective cohort study was performed to evaluate the diagnosis and treatment of LTBI in LTR. METHODS: Charts of all 547 patients who received primary liver transplantation at a University Hospital in Spain between 1988 and 1998 were reviewed. RESULTS: TST was performed in 373 patients (71%) before transplantation. The result was positive in 89 (24%). The median follow-up after transplantation was 49 months. None of the TST-positive patients developed tuberculosis (TB), but 5 out of 284 patients with negative TST (1.76%) had active TB (P=0.6). Twenty-three patients received isoniazid as treatment of LTBI according to the decision of the attending physician. None of these patients developed TB, but 4 of them (17%) presented isoniazid hepatotoxicity. Among patients who did not receive isoniazid, 2 out of 21 (9.52%) with radiologic previous TB developed active TB versus 0.44% (2/452) among the remaining patients (relative risk [RR], 27.8, 95% CI, 3.2-147). CONCLUSIONS: Treatment of LTBI with isoniazid can not be recommended to LTR on the basis of a positive TST because it is an imperfect identifier of patients at risk of TB. LTR with radiologic features of previous TB are at higher risk of posttransplant active TB. Isoniazid-related hepatotoxicity is more frequent among LTR than in the general population.     

Prevalence of latent tuberculosis infection and its risk factors in Japanese hemodialysis patients

Clinical and Experimental Nephrology - The majority of active tuberculosis (TB) cases develop from latent tuberculosis infection (LTBI). Since the risk of TB in hemodialysis (HD) patients is...     

Diagnosis and treatment of infection in cardiac transplant patients

Despite major advances in the management of rejection and the development of newer and more potent antimicrobials, infection still constitutes a major problem in transplant patients and other immunosuppressed hosts. Infectious complications in transplant patients clearly occur in two phases. The first phase includes the first 30 to 60 days after transplantation. During this period, nosocomial bacterial infections are most commonly encountered. Pulmonary, renal, and wound infections have all been encountered, and prophylactic antibiotics appear to decrease their frequency. Opportunistic infections usually do not occur during this period unless the patient undergoes treatment for acute rejection. The second phase of infectious complications usually follows the first month after transplantation. In this period, the level of immunosuppression is high, and opportunistic infections are common. Opportunistic pulmonary infections caused by P. carinii, L. pneumophila, cytomegalovirus, Aspergillus, and Nocardia spp. all are potentially life-threatening complications to the transplant patient. Aggressive diagnostic tests such as bronchoscopy, percutaneous needle biopsy, or open lung biopsy are frequently needed to make a diagnosis. Empiric broad-spectrum antimicrobial therapy is indicated in the ill patient; however, more specific therapy should be instituted once the diagnosis is confirmed.     

Mycobacterium tuberculosis infection in renal transplant recipients

Mycobacterium tuberculosis (TB) infection is more common among renal allograft recipients compared with the general population due to immunosuppression. The epidemiological risk in a country is an important determinant of transplant TB after transplantation. We retrospectively analyzed 283 renal transplant recipients who underwent renal transplantation between 1990 and 2004. We evaluated the incidence, patient and disease characteristics, prognosis, and outcome of TB infection. Tuberculosis developed in 10 (seven men and three women of mean age of 41+/-9 years) among 283 patients (3.1%). All patients were culture-positive for M tuberculosis. Although pulmonary TB was the most common presentation in the general population, 50% of patients in the study group developed extrapulmonary TB. The mean elapsed time from renal transplantation was 38 months. Three patients (1%) developed TB in the first year after transplantation. All patients were treated with a quartet of anti-TB therapy. One patient developed isoniazid-related reversible hepatotoxicity. No acute allograft rejection occurred during the anti-TB therapy. Two patients (20%) with pulmonary TB died due to dissemination of the disease. In conclusion, extrapulmonary presentations of TB are more common among renal transplant recipients with the increased risk of mortality.     

Diagnosis and treatment of tuberculosis in hemodialysis and renal transplant patients

BACKGROUND: The incidence of Mycobacterium tuberculosis in hemodialysis (HD) and renal transplant (RT) patients in developing countries is high. With the resurgence of tuberculosis in the US, insights gained in the diagnosis and treatment of this infection in HD and RT patients in developing countries should be valuable to physicians in the West. METHODS: A retrospective study of 40 cases of tuberculosis, 24 in HD patients (24/177, 13.6%) and 16 in RT patients (16/109, 14.7%) diagnosed over a period of 21 months in one center. RESULTS: The clinical features, diagnostic procedures, and management dilemmas of this group of patients are described in this report. Diabetes mellitus was the most common associated disease in both groups of patients. Fever, the most common presenting sign, was persistent low grade in 66.6% of HD patients and high intermittent in 56.2% of RT patients. Fever of unknown origin was only seen in RT patients. Pulmonary involvement was most common in both groups, presenting either as infiltrates or effusions. Tuberculous peritonitis was seen only in HD patients (33.3%). Eight HD patients were treated for tuberculosis for variable periods prior to transplantation, 4 of whom had less than 6 months of therapy. None had a recurrence of tuberculosis after transplantation. Because of the known cyclosporin-lowering effect of rifampicin resulting in an increased cost of immunosuppressive therapy, 13 patients were treated successfully with rifampicin-sparing therapy. CONCLUSION: Tuberculosis should be included in the differential diagnosis of fever in HD and RT patients, especially if fever is of unknown origin in the RT patient. M. tuberculosis in the renal transplant patient can present with high intermittent fever. Partial treatment of tuberculosis is sufficient prior to renal transplantation but treatment should be continued to completion after transplantation. If the cost of immunosuppressive therapy is prohibitive because of rifampicin, rifampicin-sparing antituberculosis therapy can be successfully employed in RT patients.     

克罗恩病患者围手术期应用英夫利西的安全性

以英夫利西为代表的新兴生物制剂的问世,使得克罗恩病的药物治疗有了突破性的进展.但是,关于英夫利西在克罗恩病围手术期的应用,目前仍存在争议.本文旨在探讨克罗恩病患者围手术期应用英夫利西对术后并发症的影响.     

Plasma leptin concentration in kidney transplant patients during early post-transplant period

Background: Leptin, is produced by adipose tissue and is presumed to be involved in the regulation of appetite and energy balance. The kidneys are involved in the inactivation of circulating leptin, and elevated plasma leptin concentrations were reported in uraemic patients. Finally, glucocorticosteroids as used in transplanted patients stimulate leptin secretion. Methods: The present study aimed to assess the relationship between plasma leptin concentration and kidney graft function in the early post-transplant period. We studied 40 successfully transplanted haemodialysed uraemic patients (27 males, 13 females, mean age 34.3±1.6 years, mean body mass index 22.5±0.5 kg/m²). The circadian rhythm of leptinaemia and insulinaemia was assessed twice: 2-4 days after kidney transplantation and 1 day before discharge from the hospital when graft function was good. Plasma leptin concentration was measured at 8 am, 4 pm, and 12 pm. The control group consisted of 21 healthy subjects (13 males, 8 females, mean age 39.4±2.5 years, mean body mass index 24.1±0.7 kg/m²). Results: Before kidney transplantation, patients had elevated plasma leptin and insulin levels. A positive correlation was found between BMI and leptinaemia and BMI and insulinaemia respectively. An inverse relationship was found between leptinaemia and age. Successful kidney transplantation was followed by a significant decline of leptinaemia i.e. from 21.5±0.1 vs 7.1±1.3 ng/ml. Kidney transplantation did not influence the circadian rhythm of leptinaemia. Conclusion: Leptinaemia was not related to the excretory graft function or immunosuppression. In addition to renal excretory function, other factors must be involved in the post-transplant decline of leptinaemia.     

Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients

BACKGROUND: Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection. METHODS: One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing. RESULTS: Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6. CONCLUSION: Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.     

Diagnosis and treatment for tuberculosis infection in liver transplant recipients: case reports

AIM: Tuberculosis (TB) infection after liver transplantation was described, diagnosed and treated herein. METHODS: We reviewed the clinical presentation, methods of diagnosis, and treatment of 2 cases of TB infection posttransplantation. RESULTS: Mycobacterium TB infection occurred in 2 of 110 (1.8%) patients undergoing liver transplantation between 2001 and 2006. Pyrexia, poor appetite, and weight loss were common presentations. The diagnosis was confirmed using lymph node biopsy and treated with standard antituberculous agents. One patient was suspected of having TB infection by clinical presentation, and tentative anti-TB drugs were used. The duration of treatment was 9 months. CONCLUSIONS: Early diagnosis and treatment are important in these patients. Careful monitoring of liver function and immunosuppressant levels are essential for patients who receive standard anti-TB drugs.     

Safety and efficacy of a quinolone-based regimen for treatment of tuberculosis in renal transplant recipients

Background

Rifampin (RFP) is a first-line antituberculosis drug, but it increases the risk of acute rejection (AR) in transplant recipients. This study evaluated whether quinolone (QNL) can replace RFP in renal transplant recipients with tuberculosis.

Methods

One hundred nine patients with active tuberculosis were included. Patients consisted of RFP (n = 91) and QNL (n = 18) groups based on the initial treatment regimen. Patients with RFP-associated adverse effects were subdivided into RFP-maintenance (RFP-M; n = 18) and QNL-conversion (QNL-C; n = 8) groups. Clinical outcomes were compared between groups.

Results

The incidence of AR was higher in the RFP group than in the QNL group (24.2% vs 5.6%). The QNL group showed significantly higher 10-year graft survival rates than the RFP group (88.1% vs 66.5%; P = .022). The QNL-C group showed significantly higher 10-year graft survival rates than the RFP-M group (87.5% vs 27.8%; P = .011). The rate of complete functional recovery after AR was higher in the QNL-C group than in the RFP-M group (50% vs 22.2%).

Conclusions

A QNL-based regimen may be safe and effective for treatment of tuberculosis and may lower the risk of graft failure in renal transplant recipients.     

Laparoscopic sleeve gastrectomy improves renal transplant candidacy and posttransplant outcomes in morbidly obese patients

Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new‐onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single‐center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011‐2016 (n = 20). Post‐LSG kidney recipients were compared with similar‐BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed‐rank test were used to compare groups. Among post‐LSG patients, mean BMI ± standard deviation (SD) was 41.5 ± 4.4 kg/m² at initial encounter, which decreased to 32.3 ± 2.9 kg/m² prior to transplantation (P < .01). No complications, readmissions, or mortality occurred following LSG. After transplantation, one patient (5%) experienced DGF, and no patients experienced NODAT. Allograft and patient survival at 1‐year posttransplantation was 100%. Compared with non‐LSG patients, post‐LSG recipients had lower rates of DGF (5% vs 20%) and renal dysfunction–related readmissions (10% vs 27.5%) (P < .05 each). Perioperative complications, allograft survival, and patient survival were similar between groups. These data suggest that morbidly obese patients with end‐stage renal disease who undergo LSG to improve transplant candidacy, achieve excellent posttransplantation outcomes.     

Microsporidia infection in transplant patients

BACKGROUND: Microsporidia are the most common cause of chronic diarrhea in patients infected with human immunodeficiency virus. Patients who have undergone organ transplantation may also be infected. The precise immune defect and the clinical picture in transplant patients have not been studied. METHODS: We report a case of microsporidia infection in a heart transplant patient and review three other cases reported in the literature. RESULTS: Infection in three solid organ transplant patients occurred when the patients were receiving immunosuppressive therapy for rejection 1.5-3 years after transplantation. Patients had chronic diarrhea, vomiting, dyspepsia, and weight loss for 1 month to 3 years. CONCLUSIONS: Microsporidia may be the cause of chronic unexplained diarrhea and gastrointestinal disturbances in transplant patients. Defects in cell-mediated immunity probably play a role in maintaining the chronicity of this infection. Specific screening requests should be made to the microbiology laboratory when microsporidia infection is suspected.