Hepatitis: Moreno A

Miró JM, Torre-Cisnero J, Moreno A, Tuset M, Quereda C, Laguno M, Vidal E, Rivero A, Gonzalez J, Lumbreras C, Iribarren JA, Fortún J, Rimola A, Rafecas A, Barril G, Crespo M, Colom J, Vilardell J, Salvador JA, Polo R, Garrido G, Chamorro L, Miranda B. · AIDS Study Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). · Enferm Infecc Microbiol Clin. · Pubmed #15970168 links to  free full text

Abstract: Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

Moreno S, García-Samaniego J, Moreno A, Ortega E, Pineda JA, del Romero J, Tural C, von Wichmann MA, Berenguer J, Castro A, Espacio R. · Department of Infectious Diseases, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain. · J Viral Hepat. · Pubmed #19215579 No free full text.

Abstract: The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.

Rivero Fernández M, Riesco JM, Moreira VF, Moreno A, López San Román A, Arranz G, Ruiz Del Arbol L. · Servicios de Gastroenterología, Hospital Ramón y Cajal. Madrid. Spain. · Rev Esp Enferm Dig. · Pubmed #19159178 links to  free full text

Abstract: Adverse drug reactions (hepatotoxicity) are a frequent cause of acute liver injury with a wide clinical and histological spectrum. An early recognition of drug-related liver disease has been considered essential in clinical practice due to potential risks. In most cases exposure discontinuation improves the clinical picture.Steroids are used in a variety of clinical settings. However, intravenous steroids have rarely been associated with hepatotoxicity. We report the case of a middle-aged woman with multiple sclerosis who received a bolus of methylprednisolone on three occasions for the management of relapsing disease, with the development of repeated episodes of elevated liver enzymes after corticoid administration. In the third episode a liver biopsy was performed, which showed acute hepatitis with bridging necrosis; such histological picture has not been described before in patients treated with intravenous steroids.

Ramos-Casals M, Cuadrado MJ, Alba P, Sanna G, Brito-Zerón P, Bertolaccini L, Babini A, Moreno A, D'Cruz D, Khamashta MA. · Laboratory of Autoimmune Diseases Josep Font, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain. · Medicine (Baltimore). · Pubmed #19011502 No free full text.

Abstract: Few studies have evaluated the impact of viral infections on the daily management of patients with systemic lupus erythematosus (SLE). We analyzed the etiology and clinical features of acute viral infections arising in patients with SLE and their influence on the diagnosis, prognosis, and treatment of SLE. Cases occurring within the last 5 years were selected from the databases of 3 large teaching hospitals. Acute viral infections were confirmed by the identification of specific antiviral IgM antibodies and subsequent seroconversion with detection of specific IgG antibodies. In autopsy studies, macroscopic findings suggestive of viral infection were confirmed by direct identification of the virus or viruses in tissue samples. We performed a MEDLINE search for additional cases reported between January 1985 and March 2008. We included 88 cases (23 from our clinics and 65 from the literature review) of acute viral infections in patients with SLE. Twenty-five patients were diagnosed with new-onset SLE (fulfillment of the 1997 SLE criteria) associated with infection by human parvovirus B19 (n = 15), cytomegalovirus (CMV; n = 6), Epstein-Barr virus (EBV; n = 3), and hepatitis A virus (n = 1). The remaining 63 cases of acute viral infections arose in patients already diagnosed with SLE: in 18 patients, symptoms related to infection mimicked a lupus flare, 36 patients, including 1 patient from the former group who presented with both conditions, presented organ-specific viral infections (mainly pneumonitis, colitis, retinitis, and hepatitis), and 10 patients presented a severe, multiorgan process similar to that described in catastrophic antiphospholipid syndrome-the final diagnosis was hemophagocytic syndrome in 5 cases and disseminated viral infection in 5. Twelve patients died due to infection caused by CMV (n = 5), herpes simplex virus (n = 4), EBV (n = 2), and varicella zoster virus (n = 1). Autopsies were performed in 9 patients and disclosed disseminated herpetic infection in 6 patients (caused by herpes simplex in 4 cases, varicella in 1, and CMV in 1) and hemophagocytic syndrome in 3. A higher frequency of renal failure (54% vs. 19%, p = 0.024), antiphospholipid syndrome (33% vs. 6%, p = 0.023), treatment with cyclophosphamide (82% vs. 37%, p = 0.008), and multisystemic involvement at presentation (58% vs. 8%, p < 0.001); and a lower frequency of antiviral therapy (18% vs. 76%, p < 0.001) were found in patients who died, compared with survivors. The most common viral infections in patients with SLE are parvovirus B19 (predominantly mimicking SLE presentation) and CMV (predominantly presenting in severely immunosuppressed patients). CMV infection may mimic a lupus flare or present with specific organ involvement such as gastrointestinal bleeding or pulmonary infiltrates. Other herpesviruses are common in immunosuppressed SLE patients and may produce a wide range of manifestations. Physicians should examine the pharynx, eyes, skin, and genitalia and should conduct serologic and molecular studies to improve early detection of viral infection in patients with SLE.

Miro JM, Aguero F, Laguno M, Tuset M, Cervera C, Moreno A, Garcia-Valdecasas JC, Rimola A, Anonymous00329. · Infectious Diseases Service, Hospital Clinic - IDIBAPS, Villarroel, 08036 Barcelona, Spain. · J HIV Ther. · Pubmed #17589393 No free full text.

Abstract: The prognosis of HIV infection has dramatically improved in recent years with the introduction of combined antiretroviral therapy. Currently, liver disease is one of the most important causes of morbidity and mortality, even more so given the high rate of hepatitis C virus co-infection in countries where drug abuse has been an important HIV risk factor. Survival of HIV-co-infected patients with end-stage liver disease (ESLD) is poor and shorter than that of the non-HIV-infected population. One-year survival of HIV-infected patients with ESLD is only around 50-55%. HIV infection is no longer a contraindication to transplantation, which is becoming a standard therapy in most developed countries. The HIV criteria used to select HIV-infected patients for liver transplantation are quite similar in Europe and North America. Current criteria state that having had an opportunistic infection (e.g. tuberculosis, candidiasis, PCP) is not a strict exclusion criterion. However, patients must have a CD4 count above 100 cells/mm3 and a plasma HIV-1 RNA viral load that is suppressible with antiretroviral treatment. More than 200 orthotopic liver transplants (OLT) in HIV-infected patients have been published in recent years and the mid-term (3-year) survival was similar to that of HIV-negative patients. The main problems in the post-transplantation period are the pharmacokinetic and pharmacodynamic interactions between antiretroviral and immunosuppressive agents and the recurrence of HCV infection, which is the principal cause of post-transplantation mortality. There are controversial results regarding mid-term survival of HIV-HCV co-infected patients compared with HCV mono-infected patients. However, one study showed a trend of poorer 5-year survival of HIV-HCV co-infected patients. There is little experience with the treatment of recurrent HCV infection. Preliminary studies showed rates of sustained virological response ranging between 15% and 20% in HIV-HCV co-infected recipients. Liver transplantation in HIV-HBV co-infected patients had a good prognosis because HBV recurrence can be successfully prevented using immunoglobulins and anti-HBV drugs. Finally, this field is evolving continuously and the indications for liver transplantation or the management of HCV co-infection may change in the future as more evidence becomes available.

Miró JM, Laguno M, Moreno A, Rimola A, Anonymous00233. · Infectious Diseases Service, Hospital Clinic-IDIBAPS, Villarroel, 08036 Barcelona, Spain. · J Hepatol. · Pubmed #16352366 No free full text.

Abstract: Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Trullás JC, Miró JM, Barril G, Ros S, Burgos FJ, Moreno A, Mazuecos A, Alvarez-Vijande R, Oppenheimer F, Carmen Sánchez M, Blanco JL, Tuset M, Torre-Cisneros J, Polo R, González J. · Hospital Clínic-IDIBAPS, Universidad de Barcelona, Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15970170 links to  free full text

Abstract: The prevalence of human immunodeficience virus (HIV) infection among patients under renal replacement therapy varies, with estimates of 1% for Europe and 1.5% for the United States. Survival in HIV infected individuals receiving renal replacement therapy has improved since the introduction of high activity antiretroviral therapy (HAART). Current experience in renal transplantation in HIV-infected patients in the United States indicates that the three-year survival rate is similar to that of HIV-negative transplant recipients, with virological and immunological control of the infection by HAART and no increase in the number of opportunistic infections or tumors. The criteria for selecting renal transplantation candidates in this population are the following: no aids-defining events, CD4 cells > 200 cells/.l and undetectable viral load under HAART. In Spain, where most of these patients are former drug abusers, a two-year period of abstinence from cocaine and heroine abuse is also required, although patients can be participating in the methadone program. The main problems in the post-transplantation period have been interactions between HAART and immunosuppressive drugs, management of hepatitis C virus (HCV) coinfection and the high rate of acute rejection. To date, seven such renal transplantations have been performed in Spain, with favorable patient and graft survival and no progression to aids.

Miró JM, Montejo M, Rufí G, Bárcena R, Vargas V, Rimola A, Bañares R, Valdivieso A, Fabregat J, Vicente E, Margarit C, Moreno A, Miralles P, Aguirrebengoa K, Xiol FX, Fortún J, Pahissa A, Laguno M, Salcedo M, Cisneros JM, Quereda C, Tuset M, Castón JJ, Torre-Cisneros J, Anonymous00290. · Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain. · Enferm Infecc Microbiol Clin. · Pubmed #15511394 links to  free full text

Abstract: According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals. Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver disease is one of the major causes of death in our country. Liver transplantation is the only therapeutic option for these patients. Accumulated experience in North America and Europe in the last five years indicates that three-year survival in HIV-positive liver transplant recipients is similar to that of HIV-negative recipients. The selection criteria for HIV transplant candidates includes the following: no history of opportunistic infections, CD4 lymphocyte count higher than 100 cells/mm3, and HIV viral load suppressible with antiretroviral treatment. In Spain, where the majority of patients are former drug abusers, complete abstinence from heroin or cocaine use during two years is also required, with the possibility of the patient being in a methadone program. To date 26 hepatic transplants have been performed in the same number of patients, with only two deaths (7%) after a median follow-up of eight months (1-28). The main problems in the post-transplantation period in all the series has been recurrent HCV infection, which is the principle cause of post-transplantation mortality, and pharmacokinetic and pharmacodynamic interactions between the antiretroviral and immunosuppressive agents. There is little experience with pegylated interferon and ribavirin treatment in this population.

Benito N, Moreno A, Pumarola T, Marcos MA. · Servicio de Infecciones. Institut Clínic d'Infeccions i Inmunologia. Hospital Clínic Universitari-IDIBAPS. Barcelona. España. · Enferm Infecc Microbiol Clin. · Pubmed #14525708 links to  free full text

Abstract: Recent years have witnessed a growing interest in the role of human herpesvirus (HHV) type 6 and type 7 as emerging pathogens or copathogens in transplant recipients. Both HHV-6 and HHV-7 belong to the beta-herpesvirus family and are closely related to another member of the family, cytomegalovirus. After the primary infection, these viruses remain latent in the human host and can reactivate after transplantation. Various clinical processes such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in association with herpesvirus. Moreover, a growing body of evidence suggests that the major impact of HHV-6 and HHV-7 reactivation in transplantation is related to indirect effects, such as their association with cytomegalovirus disease, increased opportunistic infections, and graft dysfunction and rejection. The pathogenesis of HHV-6 and HHV-7 during the post-transplantation period, the methods used for their diagnosis, and the evaluation of antiviral drugs and strategies for their prevention and treatment are now the subject of extensive research.

García-Samaniego J, Soriano V, Miró JM, Romero JD, Bruguera M, Castilla J, Esteban JI, Gonźlez J, Lissen E, Moreno A, Moreno S, Moreno-Otero R, Ortega E, Quereda C, Rodríguez M, Sánchez-Tapias JM, Anonymous00176. · Hepatology, Hospital Carlos III, Instituto de Salud Carlos III, Madrid, Spain. · HIV Clin Trials. · Pubmed #11976988 links to  free full text

Abstract: Co-infection by human immunodeficiency virus and hepatitis B and C viruses is quite common because they share similar routes of transmission. The introduction of highly active antiretroviral therapy has significantly improved the life expectancy of HIV-infected patients in the last few years. However, chronic viral hepatitis represents an emerging cause of morbidity and mortality in this population, either as a result of end-stage liver disease or as a consequence of hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus Conference was to establish specific recommendations for the management of chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic liver transplantation for co-infected individuals with end-stage liver disease was also assessed.

Quereda C, Corral I, Moreno A, Pérez-Elías MJ, Casado JL, Dronda F, Rodríguez-Sagrado MA, Hernández B, Moreno S. · Infectious Diseases, Hospital Ramón y Cajal, Madrid, Spain. · J Acquir Immune Defic Syndr. · Pubmed #18667933 No free full text.

Abstract: BACKGROUND: Mood disorders and other neuropsychiatric disorders are common adverse events limiting tolerability of alpha-interferon (IFN) therapy for hepatitis C virus (HCV). Because efavirenz (EFV) frequently produces neuropsychiatric side effects, we studied the effect of EFV in the incidence of these side effects in HIV/HCV patients receiving IFN. METHODS: Prospective cohort of HIV/HCV patients receiving IFN and ribavirin. Adverse events and concomitant medications were systematically recorded once monthly. RESULTS: Among 266 HIV/HCV patients starting a course of IFN (91% pegylated IFN) plus ribavirin, 53 (20%) received concomitant EFV and 213 (80%) did not. Most EFV patients (92%) were already on EFV before starting IFN (mean 26 months). Neuropsychiatric side effects were frequent, without significant differences between both groups (79% vs 65%, P = 0.051), and only 10 patients discontinued IFN. Mood disorders were reported more frequently in EFV patients (36% vs 23%, P = 0.046), but antidepressant therapy use was similar in both groups. The incidence of anxiety, insomnia, irritability, headache or prescription of anxiolytics or hypnotics was similar. CONCLUSIONS: Neuropsychiatric adverse events are common in HIV/HCV patients receiving IFN, usually mild or moderate. EFV may favor symptoms of mood disorders, although it was not related to an increased risk of significant depression requiring specific treatment.

Oton E, Barcena R, Garcia-Garzon S, Moreno-Zamora A, Moreno A, Garcia-Gonzalez M, Blesa C, Foruny JR, Ruiz P. · Liver Gastroenterology Service, Ramon y Cajal Hospital, Madrid, Spain. · Transplant Proc. · Pubmed #16386597 No free full text.

Abstract: The efficacy of pegylated interferon (p-IFN) and ribavirin (RB) in transplant patients is not well known. Chronic hepatitis C evolves in a more aggressive form after transplantation, causing a worse survival. Twenty-one naïve patients with recurrent chronic hepatitis C demonstrated by biopsy were treated for 48 weeks with p-IFN alpha2b (1.5 microg/kg/wk) and RB (>10.6 mg/kg/d). Quantification of RNA was performed (Amplicor Cobas 2.0 Roche) at baseline, 4, 12, 24, 48, and 72 weeks. A qualitative technique was used when quantitative levels were undetectable. At more than 1 year since liver transplantation we did not detect coinfection with human immunodeficiency virus or use steroid treatment. Among the cohort there were 16 men (76.2%). The mean overall age was 52 +/- 12 years. Time from liver transplant to treatment was 1637 +/- 1030 days. They were all infected with genotype 1. Eight patients received cyclosporine and the others tacrolimus. One patient was coinfected with hepatitis B virus and was receiving lamivudine. The mean initial histological activity index was 6.9 +/- 1.5 and fibrosis, 2.52 +/- 1.8 (Ishak). Two patients needed spleen embolization before the treatment. Two patients had to stop the treatment: one due to clinical intolerance, and the other one due to a cholangitis. In 14%, p-IFN doses were adjusted. In 32% RB was adjusted. Five (23.8%) did not respond at 24 weeks. Fourteen (66.7%) showed end-treatment responses but four relapsed at 72 weeks. A sustained viral response was achieved in 9 (42.8%). One patient died due to arterial thrombosis just after completing the treatment.

Ayala R, Grande S, Albizua E, Crooke A, Meneu JC, Moreno A, Pérez B, Gilsanz F, Moreno E, Martínez-Lopez J. · Haematology Service, Hospital 12 de Octubre, Madrid, Spain. · Liver Transpl. · Pubmed #19479801 No free full text.

Abstract: We aimed to quantify peripheral donor chimerism (DC) and to analyze its association with graft and recipient outcome. Forty-two liver transplant recipients and their respective donors were studied, providing a total of 148 posttransplantation serum samples. DC was assessed with real-time quantitative polymerase chain reaction (qPCR) to detect polymorphic markers. DC did not decrease with time post-transplantation and was higher in child recipients versus adults and in recipients of deceased donor liver transplants versus recipients of live donor liver transplants. Higher levels of DC were detected in Rh-positive blood group donors, in O blood group recipients versus A blood group recipients, and in recipients with hepatitis C virus versus recipients with alcoholic cirrhosis. High DC was associated with patients with organ damage due to recurrent disease and rejection. Stable, high levels of DC, in the absence of other major clinical events, may thus be a marker of transplantation tolerance, and this knowledge may help to tailor immunosuppressive treatment. In conclusion, qPCR is a useful technique for DC follow-up in liver transplantation, although the evolution of DC levels should be analyzed in accordance with the clinical outcome of the patient.

Vispo E, Barreiro P, Del Valle J, Maida I, de Ledinghen V, Quereda C, Moreno A, Macías J, Castera L, Pineda JA, Soriano V. · Infectious Diseases Department, Hospital Carlos III, Madrid, Spain. · Antivir Ther. · Pubmed #19430093 No free full text.

Abstract: BACKGROUND: Transient elastography (TE) is a non-invasive method that allows liver fibrosis staging on the basis of hepatic stiffness measurements. Little is known about the influence of chronic liver inflammation on the stiffness of hepatic tissue. METHODS: A total of 112 patients with chronic hepatitis C underwent a liver biopsy and TE. RESULTS: Mean values of liver stiffness (in kPa) by inflammation strata were 4.8, 6.4, 9.4 and 12.6 for A0, A1, A2 and A3, respectively, in hepatitis C virus (HCV)-monoinfected individuals (P=0.018). These figures were 8.0, 10.4, 12.9 and 12.6 for A0, A1, A2 and A3, respectively, in HIV-HCV-coinfected patients (P=0.35). In HCV-monoinfected patients with fibrosis staging F3-F4, mean liver stiffness was greater if inflammation was > or =A2 versus A0-A1 (14.6 versus 6.2 kPa; P=0.04). By contrast, no differences in liver stiffness according to inflammation were seen in HCV-monoinfected patients with <F3 or in HIV-HCV-coinfected patients regardless of liver fibrosis staging. Among HCV-monoinfected patients, mean liver stiffness was greater for alanine aminotransferase >100 versus <100 IU/l (10.5 versus 8.5 kPa; P=0.04). CONCLUSIONS: The extent of liver inflammation might affect the accuracy of TE for staging liver fibrosis, particularly in HCV-monoinfected patients with advanced fibrosis on liver biopsy and/or increased alanine aminotransferase levels.

Pérez Cachafeiro S, Del Amo J, Iribarren JA, Salavert Lleti M, Gutiérrez F, Moreno A, Labarga P, Pineda JA, Vidal F, Berenguer J, Moreno S, Anonymous00079. · National Epidemiology Centre, Instituto de Salud Carlos III, Madrid, Spain. · Clin Infect Dis. · Pubmed #19368502 No free full text.

Abstract: The prevalence of injection drug use decreased from 67.3% in 1997 to 14.5% in 2006 among Spanish patients infected with human immunodeficiency virus (HIV). A parallel decrease in the prevalence of coinfection with hepatitis C virus was observed, from 73.8% in 1997 to 19.8% in 2006. This steady decrease in the prevalence of coinfection among Spanish patients was caused by a change in transmission routes of HIV infection.

Pérez-Elías MJ, García-San Miguel L, González García J, Montes Ramírez ML, Muriel A, Machín-Lázaro JM, Martínez-Baltanás A, Zamora F, Moreno A, Martín-Dávila P, Quereda C, Gómez-Mampaso E, Moreno S. · Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain. · Clin Infect Dis. · Pubmed #19275500 No free full text.

Abstract: Tuberculosis characteristics and incidence were assessed among patients with concurrent human immunodeficiency virus infection and chronic hepatitis C virus infection who were receiving interferon-based therapy at 3 hospitals in Spain. Four of 570 patients (0.7 cases per 100 person-years; 95% confidence interval, 0.19-1.78 cases per 100 person-years) received a diagnosis of tuberculosis; all of them presented with a decrease in CD4+ cell count before diagnosis, and 3 of them received a delayed diagnosis. After tuberculosis treatment, all patients were cured.

Trullàs JC, Barril G, Cofan F, Moreno A, Cases A, Fernandez-Lucas M, Martinez-Ara J, Ceballos M, Garcia-de-Diego J, Muñiz ML, Molina J, Martínez-Castelao A, González-Garcia J, Miró JM, Anonymous00029. · Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. · AIDS Res Hum Retroviruses. · Pubmed #18834322 No free full text.

Abstract: End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

Linares L, Cervera C, Cofán F, Ricart MJ, Esforzado N, Torregrosa V, Oppenheimer F, Campistol JM, Marco F, Moreno A. · Infectious Diseases Service, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain. · Transplant Proc. · Pubmed #17889144 No free full text.

Abstract: BACKGROUND: Mutiresistant bacterial infections are an emerging problem in the nosocomial setting. Our objectives were to describe the incidence, outcome, and risk factors for acquisition of multiresistant bacteria among renal transplant recipients. METHODS: We prospectively followed patients undergoing kidney transplantation over a 3-year period. We collected demographic features, underlying chronic diseases, and main transplant characteristics and complications. Multiple antibiotic resistance was defined for the most important bacteria: Enteric gram-negative bacilli resistant to betalactamics, cephalosporins, and quinolones; Staphylococcus aureus resistant to methicillin, cotrimoxazole, and clindamcin; Enterococcus spp resistant to ampicillin and quinolones; nonfermentator bacilli resistant to all antibiotics except aminoglycosides and collistin. RESULTS: Overall, 416 patients included 65 double transplants (62 kidney-pancreas and three kidney-liver) of mean age 48.5 years, and 57% men. Infection with multiresistant bacteria was observed in 58 patients (14%). Most frequent multiresistant bacteria were: Escherichia coli (n = 33), Klebsiella spp (n = 15), Citrobacter spp (n = 8), Enterobacter spp (n = 5), Morganella morganii (n = 2), Pseudomonas aeruginosa (n = 16), Acinetobacter baumanii (n = 2), Enterococcus spp (n = 9) and methicillin-resistant S. aureus (MRSA, n = 2). Age greater than 50 years, hepatitis C virus infection, double kidney-pancreas transplantation, requirement for posttransplant hemodialysis, surgical reoperation, and requirement for nephrostomy were independent variables associated with multiresistant bacterial infection. Most used antibiotics for treatment were: carbapenems (65%), amikacin (12%), linezolid, piperacillin-tazobactam, vancomycin, collistin, and fosfomycin. Infection with multiresistant bacteria was associated with a worse prognosis (graft loss or death, 19% vs 8%, P = .009). CONCLUSIONS: The incidence of infection with multiresistant bacteria in our renal transplant cohort was high, being most frequently cephalosporin-resistant enteric gram-negative bacilli and multiresistant P aeruginosa. Methicillin-resistant S. aureus incidence was low. Infection with multiresistant bacteria conferred a worse prognosis.

Bárcena R, Moreno A, del Campo S, Muriel A, Mateos ML, Garrido E, García M, Quereda C, Moreno S, Moreno A. · Service of Gastroenterology, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain. · Antivir Ther. · Pubmed #17591030 No free full text.

Abstract: BACKGROUND: Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages. AIMS AND METHODS: To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving peg-IFN/RBV, the feasibility of predicting treatment failure using receiver operating characteristics (ROC) curves after measuring week 4 HCV RNA decreases, and to assess baseline predictors of not achieving sustained virological response (SVR). RESULTS: Peg-IFN-alpha2b was used in 84.5% of patients. Fifty-three (41%) reached SVR. The best cutoff value of HCV RNA decrease at week 4 to predict non-SVR corresponded to 1 log10 IU/ml: sensitivity and negative predictive value: 100%; specificity: 64%; positive predictive value: 66%; ROC curve area: 0.91 (95% confidence interval [CI]: 0.86-0.96). By applying this threshold, treatment could have been discontinued at week 4 in 64% of virological non-responders (49/76). By univariate analysis, baseline HCV RNA > 800,000 IU/ml (P = 0.029), older age (P = 0.011), and higher aspartate aminotransferase (AST) levels (P = 0.005) or AST/alanine aminotransferase ratio values (P = 0.04) were associated with failure. After multivariate analysis, only baseline HCV RNA >800,000 IU/ml (odds ratio [OR]: 2.12; 95% CI: 1.005-4.488; P = 0.048) and higher AST levels (OR: 1.01; 95% CI: 1.003-1.024; P = 0.011) remained statistically significant. CONCLUSIONS: The lack of > or = log10 IU/ml decrease in baseline HCV RNA at week 4 was 100% predictive of treatment failure, independently associated with HCV RNA > 800,000 IU/ml and higher AST levels.

Bárcena R, Moreno A, del Campo S, Muriel A, Mateos ML, Garrido E, García M, Quereda C, Moreno S, Moreno A. · Service of Gastroenterology, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain. · Antivir Ther. · Pubmed #17591030 No free full text.

Abstract: BACKGROUND: Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages. AIMS AND METHODS: To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving peg-IFN/RBV, the feasibility of predicting treatment failure using receiver operating characteristics (ROC) curves after measuring week 4 HCV RNA decreases, and to assess baseline predictors of not achieving sustained virological response (SVR). RESULTS: Peg-IFN-alpha2b was used in 84.5% of patients. Fifty-three (41%) reached SVR. The best cutoff value of HCV RNA decrease at week 4 to predict non-SVR corresponded to 1 log10 IU/ml: sensitivity and negative predictive value: 100%; specificity: 64%; positive predictive value: 66%; ROC curve area: 0.91 (95% confidence interval [CI]: 0.86-0.96). By applying this threshold, treatment could have been discontinued at week 4 in 64% of virological non-responders (49/76). By univariate analysis, baseline HCV RNA > 800,000 IU/ml (P = 0.029), older age (P = 0.011), and higher aspartate aminotransferase (AST) levels (P = 0.005) or AST/alanine aminotransferase ratio values (P = 0.04) were associated with failure. After multivariate analysis, only baseline HCV RNA >800,000 IU/ml (odds ratio [OR]: 2.12; 95% CI: 1.005-4.488; P = 0.048) and higher AST levels (OR: 1.01; 95% CI: 1.003-1.024; P = 0.011) remained statistically significant. CONCLUSIONS: The lack of > or = log10 IU/ml decrease in baseline HCV RNA at week 4 was 100% predictive of treatment failure, independently associated with HCV RNA > 800,000 IU/ml and higher AST levels.

Camarero C, Ramos N, Moreno A, Asensio A, Mateos ML, Roldan B. · Department of Pediatrics, Hospital Universitario Ramón y Cajal, Universidad de Alcalá de Henares, Carretera de Colmenar, 28034, Madrid, Spain. · Eur J Pediatr. · Pubmed #17464514 links to  free full text

Abstract: Hepatitis C virus (HCV) infection occurs less frequently in children than in adult patients, and the natural history, prognosis, and clinical significance of HCV infection in children are poorly defined. We report here a descriptive follow-up of the clinical course, biochemical data, and viral markers observed in 37 children with anti-HCV. Ten patients included in the study tested persistently negative for serum HCV-RNA (group 1) and 27 patients tested persistently positive (group 2). In group 1, serum alanine aminotransferase (ALT) was normal in all patients, while two patients had non-organ-specific autoantibodies. In group 2, serum ALT was elevated in 13 of 27 patients, and five patients had non-organ-specific autoantibodies. HCV genotype 1a and 1b were the most prevalent among HCV-RNA-positive patients. Twenty liver biopsies were carried out on 17 patients in our series (mean evolution time, 11.2 years; range, 3-21 years). The liver specimens showed mild necroinflammatory changes in most patients, and fibrosis was absent or low grade. Two HCV-RNA-positive patients became persistently HCV-RNA negative. Of the 26 children investigated, 7 (one in group 1, six in group 2) had a co-infection with hepatitis G virus. Conclusion Most children chronically infected with HCV were asymptomatic and presented only mild biochemical evidence of hepatic injury. Autoimmunity in the form of non-organ-specific autoantibodies was common. HCV in children induced mild changes in the liver with a low level of fibrosis and at a low rate of progression.

Cervera C, Marcos MA, Linares L, Roig E, Benito N, Pumarola T, Moreno A. · Department of Infectious Diseases, Hospital Clínic-IDIBAPS, Barcelona, Spain. · Transplantation. · Pubmed #17038915 No free full text.

Abstract: Human herpesvirus 6 (HHV-6) infection is potentially life-threatening to immunosuppressed patients. There is a lack of information regarding the risk and the clinical manifestations of primary HHV-6 infection in solid-organ transplant recipients. We prospectively evaluated patients undergoing solid organ transplantation with negative immunoglobulin (Ig) G antibodies against HHV-6 by means of HHV-6 quantitative polymerase chain reaction. Among 193 recipients, seven were HHV-6 seronegative (prevalence 3.6%). We detected a positive HHV-6 viral load in only one patient, and four patients seroconverted after one year posttransplantation. The patient with a positive HHV-6 viral load developed cholestatic hepatitis without fever and did not experience severe end-organ disease. In conclusion, our findings show a low incidence of symptomatic primary HHV-6 infection among seronegative solid-organ transplant recipients.

Moreno A, Moreno A, Pérez-Elías MJ, Quereda C, Fernández-Muñoz R, Antela A, Moreno L, Bárcena R, López-San Román A, Celma ML, García-Martos M, Moreno S. · Service of Infectious Diseases, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid 28034, Spain. · Hum Pathol. · Pubmed #16949926 No free full text.

Abstract: Syncytial giant cell hepatitis (SGCH) among adult human immunodeficiency virus (HIV)-infected patients has been rarely described. Most cases have been reported in subjects coinfected with the hepatitis C virus (HCV), but its prevalence and outcome remain unknown. We performed a retrospective analysis of all cases of SGCH among 332 liver biopsies from HIV-infected patients seen at a tertiary center in Madrid, Spain, between 1984 and March 2004. Two hundred fifty specimens were obtained from HCV-coinfected patients. There were 2 cases of SGCH, leading to an observed overall prevalence of 0.6% (0.8% when considering only HCV-coinfected patients). In addition to histological changes secondary to chronic hepatitis C, the liver cords were replaced by syncytial giant cells with up to 30 nuclei. There was no histological evidence of measles (among paramyxoviruses) or herpes viruses group infections. In patient 1, there was a progressive clinical worsening after a 3-month course of prednisone, leading to liver failure and death. His postmortem liver biopsy showed more abundant giant hepatocytes accompanied with the development of a histologic pattern of severe fibrosing cholestatic hepatitis. The second patient received a prolonged course of pegylated interferon-alpha-2b and ribavirin with clearance of syncytial giant hepatocytes despite HCV-RNA persistence. SGCH is a rare histological finding among HIV-infected patients with chronic hepatitis C. Specific treatment with pegylated interferon and ribavirin can lead to histological resolution and biochemical improvement, even in the absence of HCV-RNA clearance.

Moreno A, Moreno A, Pérez-Elías MJ, Quereda C, Fernández-Muñoz R, Antela A, Moreno L, Bárcena R, López-San Román A, Celma ML, García-Martos M, Moreno S. · Service of Infectious Diseases, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid 28034, Spain. · Hum Pathol. · Pubmed #16949926 No free full text.

Abstract: Syncytial giant cell hepatitis (SGCH) among adult human immunodeficiency virus (HIV)-infected patients has been rarely described. Most cases have been reported in subjects coinfected with the hepatitis C virus (HCV), but its prevalence and outcome remain unknown. We performed a retrospective analysis of all cases of SGCH among 332 liver biopsies from HIV-infected patients seen at a tertiary center in Madrid, Spain, between 1984 and March 2004. Two hundred fifty specimens were obtained from HCV-coinfected patients. There were 2 cases of SGCH, leading to an observed overall prevalence of 0.6% (0.8% when considering only HCV-coinfected patients). In addition to histological changes secondary to chronic hepatitis C, the liver cords were replaced by syncytial giant cells with up to 30 nuclei. There was no histological evidence of measles (among paramyxoviruses) or herpes viruses group infections. In patient 1, there was a progressive clinical worsening after a 3-month course of prednisone, leading to liver failure and death. His postmortem liver biopsy showed more abundant giant hepatocytes accompanied with the development of a histologic pattern of severe fibrosing cholestatic hepatitis. The second patient received a prolonged course of pegylated interferon-alpha-2b and ribavirin with clearance of syncytial giant hepatocytes despite HCV-RNA persistence. SGCH is a rare histological finding among HIV-infected patients with chronic hepatitis C. Specific treatment with pegylated interferon and ribavirin can lead to histological resolution and biochemical improvement, even in the absence of HCV-RNA clearance.

Oton E, Barcena R, Moreno-Planas JM, Cuervas-Mons V, Moreno-Zamora A, Barrios C, Garcia-Garzon S, Moreno A, Boullosa-Graña E, Rubio-Gonzalez EE, Garcia-Gonzalez M, Blesa C, Mateos ML. · Liver-gastroenterology Department, Ramon y Cajal Hospital, Madrid. · Am J Transplant. · Pubmed #16869810 No free full text.

Abstract: Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.