Jackrapong Bruminhent

Management of cytomegalovirus infection and disease in liver transplant recipients.

Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.

Chronic kidney disease and end-stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta-analysis.

The objective of this systematic review and meta‐analysis was to assess the clinical outcomes of Clostridium difficile infection (CDI) in patients with chronic kidney diseases (CKD) and end‐stage renal disease (ESRD).

Risk factors for cytomegalovirus reactivation after liver transplantation: Can pre-transplant cytomegalovirus antibody titers predict outcome?

Despite preexisting cytomegalovirus (CMV) immunity, CMV‐seropositive liver transplantation (LT) patients remain at risk of CMV infection. We hypothesized that the pre‐transplant CMV antibody titer correlates with the risk of CMV reactivation. We conducted a retrospective study of CMV‐seropositive LT recipients who did not receive anti‐CMV prophylaxis from 2007 to 2013. The pre‐transplant CMV immunoglobulin G (IgG) titer, which was measured with an enzyme‐linked fluorescent immunoassay, was assessed as a risk factor for CMV reactivation with multivariate Cox proportional hazards models. The population consisted of 225 CMV‐seropositive LT patients with a median age of 57 years (interquartile range, 47‐62 years). The CMV titer distributions were as follows: <60 (40%) and ≥60 AU/mL (60%). The Kaplan‐Meier estimates for CMV infection were 17% at 3 months, 18% at 6 months, and 19% at 12 months after transplantation. In a univariate analysis, a marginally significant increased risk of CMV infection was seen in LT recipients with a pre‐transplant CMV IgG titer < 60 AU/mL versus ≥ 60 AU/mL [hazard ratio (HR), 1.79; 95% confidence interval (CI), 0.98‐3.28 (P = 0.06)]. This risk was statistically significant in the subgroup of recipients who received allografts from CMV‐seropositive donors [HR, 2.21; 95% CI, 1.15‐4.26 (P = 0.02)]. In a multivariate analysis, a pre‐transplant CMV IgG titer < 60 AU/mL was significantly associated with CMV infection [HR, 3.11; 95% CI, 1.60‐6.03 (P < 0.001)]. The other risk factors were high body mass index, donor CMV seropositivity, prolonged cold ischemic time, use of an interleukin‐2 receptor antagonist for induction therapy, and high numbers of post‐transplant infections. A lower pre‐transplant CMV antibody titer is significantly associated with CMV infection after LT. Quantitative measurement of CMV‐specific humoral immunity may have a potential role in improving the CMV prevention strategy in CMV‐seropositive LT recipients. Liver Transpl 21:539–546, 2015.

Prolonged shedding of pandemic influenza A (H1N1) 2009 virus in a pancreas-after-kidney transplant recipient.

Prolonged shedding of influenza virus has been reported in immunocompromised patients. Delayed viral clearance may contribute to antiviral resistance and nosocomial transmission. We report a case of a pancreas-after-kidney transplant recipient who had detectable pandemic influenza A virus for 12 months. Pyrosequencing analysis detected the H275Y mutation, which is associated with resistance to oseltamivir.

Epidemiology, Risk Factors and Outcome of Clostridium difficile Infection in Heart and Heart-Lung Transplant Recipients

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.

The effectiveness and safety of rituximab as induction therapy in ABO-compatible non-sensitized renal transplantation: a systematic review and meta-analysis of randomized controlled trials.

Abstract Background: The objective of this systematic review and meta-analysis was to evaluate the effectiveness and safety of rituximab as induction therapy in ABO-compatible, non-sensitized renal transplantation. Methods: A literature search for randomized controlled trials (RCTs) was performed from inception through February 2015. Studies that reported relative risks or hazard ratios comparing the risks of biopsy-proven acute rejection (BPAR), graft loss, leukopenia, infection or mortality in ABO-compatible, non-sensitized renal transplant recipients who received rituximab as induction therapy versus controls were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Results: Four RCTs with 480 patients were included in the meta-analysis. Pooled RR of BPAR in recipients with rituximab induction was 0.90 (95% CI 0.50–1.60). Compared to placebo, the risk of BPAR in rituximab group was 0.76 (95% CI 0.51–1.14, I2 = 0). The risk of leukopenia was increased in rituximab group with the pooled RR of 8.22 (95% CI 2.08–32.47). There were no statistical differences in the risks of infection, graft loss and mortality at 3–6 months after transplantation with pool RRs of 1.02 (95% CI 0.85–1.21), 0.55 (95% CI 0.21–1.48) and 0.58 (95% CI 0.17–1.99), respectively. Conclusion: This meta-analysis demonstrated insignificant reduced risks of BPAR, graft loss or mortality among in ABO-compatible, non-sensitized renal transplant recipients with rituximab induction. Although rituximab induction significantly increases risk of leukopenia, it appears to be safe with no significant risk of infection.

An unusual presentation of childhood vasculitis presenting in adulthood: A challenging diagnosis of Henoch-Schönlein Purpura

Context: Henoch-Schönlein purpura (HSP), a systemic IgA vascultitis, is uncommon in adults, with an incidence rate of 0.1 to 1.2 per million in adults over 20 years old. This vasculitic syndrome can present as an uncommon cause of intestinal obstruction in older patients. We report a case of an older woman with HSP presenting with small bowel obstruction and vasculitic rash. Case Report: We report a 67-year-old woman who presented with small bowel obstruction and skin rash. Skin biopsy revealed leukocytoclastic vasculitis with +IgA granular deposition within the walls of superficial dermal vessels. Kidney biopsy confirmed the diagnosis of HSP with mild mesangial proliferative IgA nephropathy. Her abdominal pain and small bowel obstruction were improved with conservative treatment. She continued to do well with normal kidney function at a 3-month follow-up visit. Conclusion: HSP, a systemic IgA vasculitis, is a predominantly pediatric vasculitis and is uncommon in adults. In adults, the disease process is identical to that in children. However, gastrointestinal manifestation is less common in older patients, and bowel perforation and obstruction are rare. Intestinal obstruction with skin rash and renal involvement should raise suspicions of HSP.

445Epidemiology and Outcomes of Clostridium difficile Infections in Heart and Heart-lung Transplant Recipients

Background. Clostridium difficileinfection (CDI) is an important cause of diarrhea in transplant recipients, and often complicated by the use of intense immunosuppression and need for antibiotic prophylaxis. We aimed to investigate the epidemiology of CDI in heart and heart-lung transplant (HT) recipients and assessed its impact on outcomes. Methods. This is a retrospective study of HT recipients from 2000 to 2013. CDI was defined by presence of diarrhea and a positive toxigenic Clostridium difficilein stool measured by toxin enzyme immunoassay (EIA) (2000-2006) or polymerase chain reaction (2007-2013). Survival was assessed using Kaplan-Meier method. The hazard ratio (HR) for all-cause mortality was calculated using Cox proportional hazard model. Results. A total of 322 HT recipients were at risk during the 14-year study period. The median age was 53 years (IQR, 44-60); 66 % were male. During the median followup of 49 months (IQR, 1995), 27 (8.4%) patients developed CDI after transplant. Of those, six (28.5%) developed CDI within 30 days of transplant, while 21 (71.5%) patients developed CDI beyond 30 days from transplant. Two (7.4%) had hypervirulent NAP1/BI/027 strain. Six (22%) had at least 1 episode of recurrent CDI. No patient required colectomy or died from CDI. However, patients with CDI had worse overall survival compared to non-CDI patients (log rank test; p < 0.01) (Figure 1).In univariate analysis, the predictors of mortality in HT recipients were: CDI anytime after transplant [HR 2.33; 95% CI, 1.14-4.32 (p = 0.02)], female donor [HR 1.83; 95% CI, 1.09-3.03 (p = 0.02)], older donor age per 1 year increase [HR 1.05; 95% CI, 0.99-1.03 (p = 0.09)] and combined heart-lung transplant [HR 2.13; 95% CI, 0.82-4.60 (p = 0.11)].In a multivariate analysis, CDI anytime after transplant remained significantly associated with all-cause mortality [HR 2.23; 95% CI, 1.07-4.27 (p = 0.03)]. Conclusion. CDI is a common cause of diarrhea in HT patients. CDI is significantly associated with, and an independent predictor for, increased mortality after heart transplantation. Efforts to prevent CDI may improve survival of HT recipients. Disclosures. All authors: No reported disclosures.

604Risk Factors for Cytomegalovirus (CMV) Reactivation in CMV-seropositive Liver Transplant Patients

Background. CMV causes significant morbidity in liver transplant (LT) recipients. Despite pre-existing CMV immunity, CMV-seropositive LT patients remain at risk of CMV reactivation. We aimed to investigate variables associated with CMV reactivation in CMV-seropositive LT patients. Methods. A retrospective study of CMV-seropositive LT recipients in 2007-2013 who did not receive anti-CMV prophylaxis was performed. CMV reactivation was defined as presence of CMV regardless of symptoms. CMV was measured by polymerase chain reaction. Cox proportional hazard model was used to assess risk factors for CMV reactivation in CMV-seropositive LT patients. Results. There were 231 CMV-seropositive LT patients with median age of 55.8 years (IQR, 46-62); 56% were male. During the median follow-up of 1147 days (IQR, 537-1792), 43 patients (18.6%) had CMV reactivation. Of those, twenty three (53.5%) had asymptomatic CMV infection, 5 (11.6%) had CMV syndrome, and 15 (34.9%) had tissue-invasive disease [GI (13), liver (1), lung (1)]. The median onset was 43 days (IQR 33-74) post-transplant. In univariate analysis, the 5 potential factors associated with CMV reactivation were: higher recipient body mass index per 1 kg/m increase [HR 1.44; 95%CI, 1.09 to 1.89 (P = 0.01)], recipient pre-transplant CMV IgG titer <60 AU/mL [HR 1.75; 95%CI, 0.96 to 3.19 (P = 0.069)], older donor age per 10 years increase [HR 1.20; 95%CI, 1.02 to 1.43 (P = 0.03)], CMV donor seropositivity [HR 4.45; 95%CI, 1.87 to 13.13 (P = <0.001)], and induction with anti-IL2 antagonist [HR 2.46; 95%CI, 1.28 to 4.67 (P = 0.007)]. In adjusted model, pre-transplant CMV IgG titer <60 AU/mL was significantly associated with CMV reactivation [HR, 1.98; 95%CI, 1.07 to 3.66 (P = 0.03)]. Conclusion. Several donor and recipient factors correlate with CMV reactivation in CMV-seropositive LT recipients. A low pre-transplant CMV IgG titer is significantly associated with CMV reactivation. Quantitative measurement of CMV specific humoral immunity has a potential to optimize CMV prevention strategy in CMV-seropositive LT recipients. Disclosures. All authors: No reported disclosures.

Outcomes of patients with cytomegalovirus viremia at the time of liver transplantation

Cytomegalovirus (CMV) infection has been associated with poor outcomes after liver transplantation. Whether it is safe to perform transplantation for patients with active CMV viremia is not known. Here we report the outcomes of 6 patients with CMV viremia immediately before or at the time of liver transplantation. Data from these patients indicate that CMV can be adequately controlled with antiviral therapy, although patients appear to be at higher risk for indirect effects of CMV such as other opportunistic infections and liver allograft dysfunction. Liver Transpl 20:1029–1033, 2014.