Citations

Abstract Background Mycobacterium tuberculosis ( TB ) is a common pathogen worldwide, and it may cause significant infection after solid organ transplantation ( SOT ). We reviewed all reported TB cases to provide an update on its epidemiology, clinical presentation, management, and outcome after SOT . Methods MEDLINE , EMBASE , and OVID were reviewed from January 1, 1998, to December 31, 2016, using keywords tuberculosis and solid organ transplant or transplantation. Results There were 187 publications reporting 2082 cases of TB among kidney (n = 1719), liver (n = 253), heart (n = 77), lung (n = 25), and kidney‐pancreas (n = 8) recipients. Among cohort studies, the median incidence was 2.37% (range, 0.05%‐13.27%) overall. Most TB disease was considered reactivation of latent infection, occurring beyond the first year after SOT . Early‐onset cases were seen among donor‐derived TB cases. Fever was the most common symptom. Radiologic findings were highly variable. Extrapulmonary and disseminated TB occurred 29.84% and 15.96%, respectively. Multidrug‐resistant TB was rare. Treatment using 4 or 5 drugs was commonly associated with hepatotoxicity and graft dysfunction. All‐cause mortality was 18.84%. Conclusions This large review highlights the complexity of TB after SOT . Reactivation TB , donor‐transmitted infection, extrapulmonary involvement, and disseminated disease are common occurrences. Treatment of TB is commonly associated with hepatotoxicity and graft dysfunction.

AbstractCytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA‐approved PCR assay (Cobas® AmpliPrep/Cobas TaqMan® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy‐proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/106 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients.

Abstract Background Quantification of cytomegalovirus (CMV) deoxyribonucleic acid (DNA) has important diagnostic, prognostic, and therapeutic implications in the management of transplant recipients. We aimed to assess a viral load in plasma and whole blood that distinguishes CMV disease from asymptomatic infection in a cohort of solid organ and hematopoietic stem cell transplantation. Methods We prospectively measured and compared CMV viral load in paired plasma and whole blood samples collected from transplant recipients with CMV infection and disease. Cytomegalovirus viral loads were determined by a commercially available US Food and Drug Administration-approved quantitative assay (COBAS AmpliPrep/COBAS TaqMan CMV Test [CAP/CTM CMV]) calibrated to the first World Health Organization International Standard for CMV DNA quantification. Results Moderate agreement of CMV viral load was observed between plasma and whole blood, with 31% of samples having discordant findings, particularly among samples with low DNA levels. Among the subset of samples where both paired samples had quantifiable levels, we observed a systematic bias that reflected higher viral load in whole blood compared with plasma. Based on receiver operating curve analysis, an initial plasma CMV viral load threshold of 1700 IU/mL in solid organ transplant recipients (sensitivity 80%, specificity 74%) and 1350 IU/mL in allogeneic hematopoietic stem cell transplant recipients (sensitivity 87%, specificity 87%) distinguished CMV disease and asymptomatic infection. Conclusions This study identifies standardized viral load thresholds that distinguish CMV disease from asymptomatic infection using CAP/CTM CMV assay. We propose these thresholds as potential triggers to be evaluated in prospective studies of preemptive therapy. Plasma was better than whole blood for measuring viral load using the CAP/CTM CMV assay.

AbstractHuman herpesvirus 6 (HHV‐6A and HHV‐6B) can cause primary infection or reactivate from latency in liver transplant recipients, which can result in a variety of clinical syndromes, including fever, hepatitis, encephalitis and higher rates of graft dysfunction as well as indirect effects including increased risks of mortality, CMV disease, hepatitis C progression and greater fibrosis scores. Although HHV‐6 infection is currently diagnosed by quantifying viral DNA in plasma or blood, biopsy to demonstrate histopathological effects of HHV‐6 remains the gold standard for diagnosis of end‐organ disease. HHV‐6 reactivation may be restricted to the infected organ with no evidence of active infection in the blood. HHV‐6 infections in liver transplant patients are mostly asymptomatic, but clinically significant tissue‐invasive infections have been treated successfully with ganciclovir, foscarnet or cidofovir. Inherited chromosomally integrated HHV‐6 (ciHHV‐6), in either the recipient or the donor organ, may create confusion about systemic HHV‐6 infection. Recipients with inherited ciHHV‐6 may have an increased risk of opportunistic infection and graft rejection. This article reviews the current scientific data on the clinical effects, risk factors, pathogenesis, diagnosis and treatment of HHV‐6 infections in liver transplant recipients.

AbstractThe epidemiology of infection after liver transplantation for hilar cholangiocarcinoma has not been systematically investigated. In this study of 124 patients, 255 infections occurred in 105 patients during the median follow‐up of 4.2 years. The median time to first infection was 15.1 weeks (IQR 1.6‐62.6). The most common sites were the abdomen, bloodstream, and musculoskeletal system. Risk factors for any post‐transplant infection were pre‐transplant VRE colonization (Hazard Ratio [HR] 1.9, P=.002), living donor transplantation (HR 6.6, P<.001), longer cold ischemia time (HR 1.05 per 10 minutes, P<.001), donor CMV seropositivity (HR 2.2, P<.001), hepatic artery thrombosis (HR 2.6, P=.005), biliary stricture (HR 3.8, P=.002), intra‐abdominal fluid collection (HR 4.2, P<.001), and re‐operations within 1 month after transplantation (HR 1.7, P=.020). Abdominal infections were independently associated with hemodialysis requirement within 1 month after transplantation (HR 5.6, P=.006), hepatic artery thrombosis (HR 3.3, P=.007), biliary stricture (HR 5.2, P<.001), and abdominal fluid collection (HR 3.7, P=.0002). Bloodstream infections were independently associated with allograft ischemia (HR 17.8, P<.001), biliary stricture (HR 6.5, P=.005), and recipient VRE colonization (HR 4, P<.001). Abdominal infections (HR 2.3, P=.02) and Clostridium difficile infections (HR 4.6, P=.01) were independently associated with increased mortality.

Abstract Background Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors, and outcome of Clostridium difficile infection ( CDI ) in heart and heart‐lung transplant ( HT ) recipients. Methods This is a retrospective study from 2004 to 2013. CDI was defined by diarrhea and a positive toxigenic C. difficile in stool measured by toxin enzyme immunoassay (2004‐2006) or polymerase chain reaction (2007‐2013). Cox proportional hazards regression was used to model the association of risk factors with time to CDI and survival with CDI following transplantation. Results There were 254 HT recipients, with a median age of 53 years ( IQR , 45‐60); 34% were female. During the median follow‐up of 3.1 years ( IQR , 1.3‐6.1), 22 (8.7%) patients developed CDI . In multivariable analysis, risk factors for CDI were combined heart‐lung transplant ( HR 4.70; 95% CI , 1.30‐17.01 [ P =.02]) and retransplantation ( HR 7.19; 95% CI , 1.61‐32.12 [ P =.01]). Acute cellular rejection was associated with a lower risk of CDI ( HR 0.34; 95% CI , 0.11‐0.94 [ P =.04]). CDI was found to be an independent risk factor for mortality ( HR 7.66; 95% CI , 3.41‐17.21 [ P <.0001]). Conclusions Clostridium difficile infection after HT is more common among patients with combined heart‐lung and those undergoing retransplantation. CDI was associated with a higher risk of mortality in HT recipients.

The epidemiology of infections after living donor liver transplantation (LDLT) is limited. We aimed to study the epidemiology and risk factors of infections after LDLT. The medical records of 223 adult patients who underwent LDLT from January 1, 2000 to August 31, 2015 were reviewed for all infections occurring up to 1 year. We estimated the cumulative incidence of infection using the Kaplan‐Meier product limit method. Risk factors were analyzed with time‐dependent Cox regression modeling. The majority of patients were Caucasian (94.6%) and male (64.6%), and the median age at transplantation was 55 years. The most common indication for transplantation was primary sclerosing cholangitis (37.7%). A total of 122 patients developed an infection during the follow‐up period (1‐year cumulative event rate of 56%), with the majority (66%) of these occurring within 30 days after transplantation.Enterococcus sp. was the most frequent pathogen identified. Multivariate analysis showed that increased Model for End‐Stage Liver Disease (MELD) score (per 10‐point change: hazard ratio [HR], 1.59), history of recurrent infections prior to transplant (HR, 2.01), Roux‐en‐Y anastomosis (HR, 2.37), increased log‐number of packed red blood cell transfusions (HR, 1.39), and biliary complications (HR, 4.26) were independently associated with a higher risk of infection. Infections occur commonly after LDLT, with most infections occurring early and being related to the hepatobiliary system. Higher MELD scores, the type of biliary anastomosis, presence of biliary complications, and prior pretransplant infections are independently associated with a higher risk for infections.Liver Transplantation 23 465–4772017 AASLD.