Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

Seroprevalencia de virus hepatitis E en donantes de sangre en un hospital universitario en Chile / Hepatitis E virus seroprevalence in blood donors in a university hospital in Chile

Resumen En Chile, existen escasos estudios de seroprevalencia de anticuerpos IgG anti virus hepatitis E (VHE) en bancos de sangre, entre 4 y 8%. El desarrollo de nuevas técnicas con mayor sensibilidad y especificidad, dan cuenta de un aumento de la seroprevalencia de VHE en diversos países, siendo desconocido el estado actual en Chile. En el presente estudio, determinamos la seroprevalencia de IgG anti VHE en donantes de sangre del Hospital Clínico Universidad de Chile, con técnicas de ELISA de última generación. De un total de 186 muestras, recolectadas el año 2014, 56 (30,1%) resultaron positivas, sin diferencias de género, pero con un incremento significativo con la edad (p < 0,001). Estos resultados muestran un aumento en la seroprevalencia de VHE en donantes de sangre realizados con inmunoensayos de mayor sensibilidad.

In Chile, there are few studies about seroprevalence of IgG antibodies against hepatitis E virus (HEV) in blood banks, between 4 and 8%. The development of new techniques with greater sensitivity and specificity, account for an increase in the seroprevalence of HEV in various countries, the current status in Chile being unknown. In the present study, we determined the seroprevalence of anti-HEV IgG in blood donors of the Clinical Hospital University of Chile, with last generation ELISA techniques. Out of a total of 186 samples, collected in 2014, 56 (30.1%) were positive, without gender differences, but with a significant increase with age (p < 0.001). These results show an increase in the seroprevalence of HEV in blood donors performed with immunoassays of greater sensitivity.

El polimorfismo rs12979860 C> T en el gen Interferón lambda 4 no está asociado a riesgo de fibrosis hepática en pacientes chilenos con hepatitis crónica por virus C / Interferon Lambda 4 RS12979860 C> T polymorphism is not associated with liver fibrosis in patients with hepatitis C

Background. Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. Aim: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. Material and Methods: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). Results: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. Conclusions: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

Seroconversión frente a primovacunación reforzada contra hepatitis B en niños con cáncer / Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer

Introducción: La respuesta inmune a los antígenos de las vacunas está disminuida en los niños con cáncer. El objetivo de este estudio fue evaluar la seroconversión frente a vacuna ADN recombinante contra hepatitis B al momento del inicio de la quimioterapia y/o remisión en niños con cáncer. Pacientes y método: Estudio prospectivo, bicéntrico, controlado, no aleatorizado de niños con diagnóstico reciente de cáncer pareados con niños sanos. Los casos fueron vacunados a tiempo 0, 1 y 6 meses, a dosis de 20 y 40 μg si eran < ó > 10 años, respectivamente, con vacuna ADN recombinante contra hepatitis B, en el momento del diagnóstico en el caso de los tumores sólidos y luego de la remisión en el caso de los tumores hematológicos. El grupo control recibió el mismo esquema, con dosis de 10 o 20 μg respectivamente. Se midieron anticuerpos séricos anti-HBs a los 2, 8 y 12 meses posvacunación. Seroconversión se definió como títulos anti-HBs > 10 mUI/ml al octavo mes. Resultados: Un total de 78 niños con cáncer y 25 controles fueron evaluados con títulos anti-HBs al octavo mes. La tasa de seroconversión fue de 26,9%, en niños con cáncer, sin diferencia por edad, género ni tipo de tumor (p = 0,13; 0,29; y 0,44, respectivamente), y de 100% en el grupo control (p < 0,0001, comparado con los niños con cáncer). En el seguimiento a los 12 meses solo el 31,9% de los niños con cáncer presentaba títulos anti-HBs > 10 mUI/ml. Conclusiones: La vacunación contra hepatitis B con vacuna ADN recombinante, con esquema reforzado de 3 dosis, en el momento del inicio de la quimioterapia y/o remisión provee una respuesta inmune insuficiente en la mayoría de los niños con cáncer. En esta población debieran evaluarse vacunas de tercera generación, con adyuvantes más inmunogénicos, esquemas reforzados a los 0, 1, 2 y 6 meses, medición de títulos de anticuerpos al octavo y duodécimo mes, eventual uso de refuerzos y reevaluación de inmunogenicidad si correspondiese.

Introduction: Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. Patients and method: Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. Results: A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml. Conclusions: Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12 h to evaluate the need for further booster doses.

Eventos adversos en la terapia farmacológica de la enfermedad inflamatoria intestinal / Adverse events associated with the treatment of inflammatory bowel disease

Background: The purpose of inflammatory bowel disease (IBD) treatment is to achieve resolution of symptoms and remission of disease with a minimum of adverse events (AE). Aim: To report AE of different prescriptions used for the treatment of IBD. Material and Methods: Analysis of a registry of patients with IBD held at a private clinic from 1976 to 2013. All used medications, the occurrence and severity of AE were recorded. Results: The records of 346 patients aged 16 to 86 years, 74% with ulcerative colitis, were analyzed. The most commonly type of medications prescribed were 5-aminosalicylates (5-ASAs) in 329 patients (92%), followed by adrenal steroids in 218 (61%). Forty nine AE were recorded in the same number of patents (14%). These were more common in patients with Crohn disease (n = 19, 21%). An univariate analysis, demonstrated that extra-intestinal manifestations, hospitalizations secondary to IBD crisis, requirement of surgery and treatment with steroids, immunosuppressants or biologic agents were significantly associated with the presence of AE. AEs were more common with immunosuppressants, followed by 5-ASAs and steroids. Discontinuation of therapy was required in 79, 100 and 43% of patients taking these medications, respectively. Twenty percent of AEs were severe. Leukopenia and pancytopenia along with alopecia were the most common AEs attributable to azathioprine. Conclusions: The occurrence of AEs in patients with IBD is uncommon. Even inmunosuppressants or biologic agents have a low rate of AE and most of them mild.

Enfermedad inflamatoria intestinal a partir de una experiencia local / Inflammatory bowel disease. Experience in 316 patients

Background: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. Aim: To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. Patients and Methods: Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. Results: Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p = 0.001). There was a trend towards a higher requirement of surgery until 2006. Subsequently there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. Conclusions: An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.

Resultados del tratamiento con peginterferón alfa-2a y ribavirina en pacientes con hepatitis crónica C / Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C

Background: The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. Aim: To report our experience in the treatment of chronic hepatitis C. Material and Methods: Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg /day. Results: Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4 percent of patients, respectively. Twenty four patients (46 percent), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that infl uenced the response to treatment. Conclusions: Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.

Metástasis pancreáticas tardías secundarias a cáncer de células renales: Caso clínico / Pancreatic metastasis from renal cell carcinoma: A case report

We report the case of a 60 year old woman with multiple pancreatic nodules found on abdominal computed tomography. Thirteen years earlier she had undergone a left nephrectomy for renal cell carcinoma. The patient underwent surgery with a preoperative diagnosis of multifocal metastatic or neuroendocrine tumor. At surgery, two metastatic nodules of renal cell carcinoma were found and excised. After four years of follow up there is no evidence of recurrence.

Seroprevalencia de virus hepatitis B en niños con cáncer en tratamiento quimioterápico en 6 hospitales de Santiago de Chile / Seroprevalence of hepatitis B virus in children with cancer under chemotherapy in 6 hospitals of Santiago, Chile

Background: Children under oncological therapy are at risk of infection by hepatitis B virus (HBV). Aim: To determine the prevalence of infection of HBV in children with cancer who have undergone chemotherapy or have had a hematopoietic stem cell transplant. Material and methods: Collaborative, multi-centric study. Serum samples were collected from 281 children with cancer and episodes of febrile neutropenia, from 6 hospitals belonging to the public health network in the Metropolitan Region, between June 2004 and August 2006. These samples were stored at -70-'C. In September 2006, 200 samples were randomly chosen and 170 analyzed to determine hepatitis B virus surface antigen (HBsAg) and anticore total antibodies (anti HBc) by fluorescent ELISA (Enzyme Linked Immunosorbent Assay). In five cases in which a low volume of sample was available, only one marker was studied (HBsAg in two and anti HBc in three). Results: Samples carne from children aged 4 months to 18 years, 104 males (61 percent). They had received an average of 38 transfusions (range 3-107) from 65 donors (range 3-345). Twelve children were found positive for some marker of HBV: HBsAg in three (1.8 percent) and anti HBc in ten (7 percent). In 5 patients that had negative HBsAg and positive anti HBc, anti surface antigen antibodies (anti HBs) were determined and resulted positive in four Conclusions: The prevalence of HBV in this sample was 7 percent if both serologic markers are considered and 1.8 percent if only HBsAg is considered.

Registro de incidencia de hepatitis crónica: Asociación Chilena de Hepatología: período 1994-1996 / Chronic hepatitis incidence record: Chilean Hepatology Association (1994-1996)

La Asociación Chilena de Hepatología creó un registro de casos nuevos de hepatitis crónicas diagnosticadas con biopsia hepática entre los años 1994 y 1996. Se registran y clasifican de acuerdo a su etiología 106 pacientes altamente seleccionados con hepatitis crónica provenientes de la regiones metropolitana, quinta y segunda. De acuerdo a la etiología: 13 por ciento criptogénicas y 7 por ciento Virus B. La presencia de cirrosis al diagnóstico fue de 30 por ciento para las de origen viral C y 24 por ciento para las de origen autoinmune lo que podría afectar la respuesta a las alternativas terapéuticas. De acuerdo a estos resultados, deberíamos promover el diagnóstico más temprano en pacientes con alteraciones de laboratorio asintomáticas o notificando a los donantes de sangre en los que detecta alguna infección viral. En ausencia de otras instancias que realicen este tipo de evaluaciones, sugerimos repetir o mantener registros en lo posible de cobertura nacional, tanto para los pacientes con hepatitis crónica como para otras patologías hepáticas.

Beta-2 microglobulina (B-2M) en hepatitis virales / Beta-2 microglobulin (B-2M) in viral hepatitis

Como se sabe, Beta-2 Microglobulina es parte de los antígenos HLAI de membrana celular y participa en la respuesta inmune citotóxica. Su concentración en el suero aumenta en varias enfermedades malignas, en procesos inflamatorios y en insuficiencia renal. En este trabajo se miden los niveles séricos de Beta-2 Microglobulina en pacientes con hepatitis viral usando una prueba de enzima inmunoensayo, los resultados se correlacionan con la evolución de la enfermedad. Altos niveles de Beta-2 Microglobulina se encontraron en todos los grupos de pacientes estudiados, especialmente en hepatitis aguda. Estos altos niveles tienden a normalizarse con la mejoría del cuadro clínico en 5 de los 10 casos que se estudiaron. Beta-2 Microglobulina fue medida en el momento del diagnóstico y después en intervalos de 5 a 90 días entre la 1ª y 2ª muestra. Los resultados sugieren que Beta-2 microglobulina puede ser un indicador de hepatitis. La persistencia de la respuesta inmune podría estar representada por los altos niveles de estas proteínas