Manuela Aguilar-Guisado

HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)‐related end‐stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV‐infected and HIV‐uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV‐coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV‐monoinfected and 100 (56%) HCV/HIV‐coinfected subjects died during the follow‐up. The median survival time of HIV‐infected and HIV‐uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV‐infected patients was 2.26 (1.51‐3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53‐3.31]); Child‐Turcotte‐Pugh class B versus class A (1.95 [1.41–2.68]) and class C versus class A (2.78 [1.66–4.70]); hepatitis D virus infection (1.56 [1.12–4.77]); model for end‐stage liver disease score, (1.05 [1.01‐1‐11]); more than one simultaneous decompensation (1.23 [1.12–3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26–3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV‐related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV‐coinfected subjects. (HEPATOLOGY 2005.)

Clinical progression of hepatitis C virus–related chronic liver disease in human immunodeficiency virus–infected patients undergoing highly active antiretroviral therapy

Little is known about the natural history of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)‐coinfected subjects under highly active antiretroviral therapy (HAART). The objectives of this study were to obtain information about the mortality, the incidence of hepatic decompensations, and the predictors thereof in this population. In a multicenter cohort study, the time to the first hepatic decompensation and the survival of 1,011 antiretroviral naïve, HIV/HCV‐coinfected patients who started HAART and who were followed prospectively were analyzed. After a median (Q1‐Q3) follow‐up of 5.3 (2.9–7.1) years, 59(5.83%) patients developed a hepatic decompensation and 69 (6.82%) died, 30 (43%) of them because of liver disease. The factors independently associated [HR (95% CI)] with the occurrence of hepatic decompensations were age older than 33 years [2.11 (1.18–3.78)], female sex [2.11 (1.07–4.15)], Centers for Disease Control stage C [2.14 (1.24–3.70)], a diagnosis of cirrhosis at baseline [10.86 (6.02–19.6)], CD4 cell gain lower than 100/mm3 [4.10 (2.18–7.69)] and less than 60% of the follow‐up with undetectable HIV viral load [5.23 (2.5–10.93)]. Older age [2.97 (1.18–7.50)], lack of HCV therapy [11.32 (1.44–89.05)], hepatitis D virus coinfection [16.15 (2.45–106.48)], a diagnosis of cirrhosis at recruitment [13.69 (5.55–34.48)], hepatic encephalopathy [62.5 (21.27–200)] and lower CD4 cell gain [3.63 (1.45–9.09)] were associated with mortality due to liver failure. Conclusion: End‐stage liver disease is the primary cause of death in HIV/HCV‐coinfected patients under HAART. Higher increase of CD4 cell counts, lack of markers of serious liver disease and therapy against HCV are factors associated with better hepatic outcome. (HEPATOLOGY 2007.)

Pneumonia after lung transplantation in the RESITRA Cohort: a multicenter prospective study.

The aim of the present study is to evaluate the epidemiology, etiology and prognosis of pneumonia in lung transplant (LT) recipients. This is a prospective, multicenter study of a consecutive cohort of LT recipients in Spain. From September 2003 to November 2005, 85 episodes of pneumonia in 236 LT recipients were included (incidence 72 episodes per 100 LT/year). Bacterial pneumonia (82.7%) was more frequent than fungal (14%) and viral pneumonia (10.4%). The most frequent microorganisms in each etiological group were Pseudomonas aeruginosa (n = 14, 24.6%), CMV (n = 6, 10.4%) and Aspergillus spp. (n = 5, 8.8%). Incidence of Aspergillus spp. and CMV pneumonia is lower than previously reported, probably due to the spread of universal prophylaxis. Pneumonia caused by viruses appeared significantly later than pneumonia due to gram‐negative bacilli, fungi and those without known etiology (p < 0.01, p = 0.03 and p = 0.02, respectively). The routine use of ganciclovir has changed the natural history of CMV infection, so that pneumonia appears later, once prophylaxis is suspended. The probability of survival during the first year of follow‐up was significantly higher in the multivariate analysis in LT recipients who did not have a pneumonia episode compared with those that had at least one episode (p < 0.01).

Natural History of Compensated Hepatitis C Virus-Related Cirrhosis in HIV-Infected Patients

OBJECTIVEnTo provide information about the incidence and predictors of liver decompensation and death due to liver failure in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis.nnnMETHODSnProspective cohort study of 154 HIV-HCV-coinfected patients with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis. We evaluated time from diagnosis to the first liver decompensation and death from liver disease, as well as predictors of these outcomes.nnnRESULTSnThirty-six patients (23.4%) developed liver decompensation. The incidence of liver decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI], 4.18-9.38 cases per 100 person-years). Factors independently associated with liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI, 1.09-10.53; P = .035), baseline CD4 cell counts <or=300 cells/mm3 (HR, 2.12; 95% CI, 1.14-5.04; P = .021), CPT score 6 versus 5 (HR, 3.33; 95% CI, 1.39-7.69; P = .007), and a diagnosis of cirrhosis based on data other than biopsy or transient elastography (HR, 2.09; 95% CI, 1.05-4.16; P = .036 ). Fifteen patients (9.7%) died; 11 (73%) of these 15 died from liver disease (mortality due to liver failure, 2.44 deaths per 100 person-years; 95% CI, 1.21-4.36 deaths per 100 person-years). Hepatic encephalopathy as the first liver decompensation (HR, 20.67; 95% CI, 2.71-157.57; P = .003), baseline CD4 count <or=300/mm3 (HR, 0.24; 95% CI, 0.07-0.78; P = 0.17), and baseline CPT score 6 (HR, 4.50; 95% CI, 1.63-12.37; P = .004) were independently associated with liver-related death.nnnCONCLUSIONSnThe incidence of clinical liver events in HIV-HCV-coinfected patients with CPT class A compensated cirrhosis is close to that previously reported in HCV-monoinfected patients. Lower baseline CD4 cell counts, lack of therapy against HCV, and higher CPT score are the factors related to the occurrence of clinical liver events. Minimal changes in CPT score have strong impact in the prognosis of this population.

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

Background Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients’ risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and Methods This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Results Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Conclusions Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials.

Patterns of Infection in Patients With Myelodysplastic Syndromes and Acute Myeloid Leukemia Receiving Azacitidine as Salvage Therapy. Implications for Primary Antifungal Prophylaxis

Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens.

Empirical antifungal therapy in selected patients with persistent febrile neutropenia.

Universal empirical antifungal therapy (EAT) in patients with unexplained persistent febrile neutropenia (PFN) is the standard of care, but EAT could be applied in selected patients on the basis of clinical criteria and risk factors. A prospective interventional study was carried out to analyse the incidence and related mortality of invasive fungal infection (IFI) in patients with PFN according to whether or not EAT was indicated. EAT was indicated according to the following criteria: (a) severe sepsis or septic shock; (b) focused infection: lung, central nervous system, sinus, abdominal or skin; (c) individualized clinical decision in patients at high risk. Sixty-six (19%) of 347 episodes of febrile neutropenia fulfilled PFN criteria, 97% with a haematological malignancy. Just 26 (39.4%) were treated with EAT. The overall IFI incidence was 4.5%. In the group that received EAT, three patients developed IFI (11.5%), in comparison with none in the group that did not receive it (P=0.04, RR 2.7:1.9–3.8). IFI-related mortality was null in the group that did not receive EAT and 8% (two of 26 patients) in the group that received EAT. These data suggest that in patients with PFN, EAT in selected patients may be safe and avoid unnecessary antifungal therapy.

Prospective study of infectious complications in allogeneic hematopoietic stem cell transplant recipients.

Martín‐Peña A, Aguilar‐Guisado M, Espigado I, Parody R, Cisneros JM. Prospective study of infectious complications in allogeneic hematopoietic stem cell transplant recipients.u2028Clin Transplant 2011: 25: 468–474.

Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study.

Aguilar‐Guisado M, Jiménez‐Jambrina M, Espigado I, Rovira M, Martino R, Oriol A, Borrell N, Ruiz I, Martín‐Dávila P, de la Cámara R, Salavert M, de la Torre J, Cisneros JM, on behalf of Spanish Network for Research in Infectious Diseases. Pneumonia in allogeneic stem cell transplantation recipients: a multicenter prospective study. u2028Clin Transplant 2011: 25: E629–E638.

Antifungal Combination Therapy for Invasive Aspergillosis

The outcome of invasive aspergillosis (IA) continues to be associated with significant attributable mortality, especially in patients with hematological malignancies and in hematopoietic stem cell transplant recipients. In this context, antifungal combined therapy (ACT) has become an emerging strategy against IA. In an attempt to evaluate the benefits of ACT, a large number of experimental studies, clinical series, and randomized trials have been performed, with varying results. In addition, several controlled trials have been registered; however, in most cases, their final results have not been made available. In summary, there is an imbalance between the lack of published evidence regarding the benefits of ACT and its extensive and increasing use in current clinical practice, despite its associated cost. Here, we present a critical analysis of the available information regarding ACT for the treatment of IA as well as the authors opinion with respect to its use.