Marcelo Corti

Hepatitis C (HCV) genotype and viral titer distribution among Argentinean hemophilic patients in the presence or absence of human immunodeficiency virus (HIV) co‐infection

Hepatits C (HCV) infection is frequent among hemophilic patients treated with non‐inactivated factor‐concentrates. Both HCV genotype and viral load have been suggested to be important prognostic markers of disease progression and treatment outcome. In addition, co‐infection with the human immunodeficiency virus (HIV) has been associated with increased level of HCV replication and higher risk of developing liver failure. Thus, HCV genotype, viral load, and HIV co‐infection are important factors in HCV infection.

Linfomas primarios del sistema nervioso central en pacientes con sida

Introduccion El linfoma primario es la neoplasia mas frecuente del sistema nervioso central (SNC) en pacientes con sida. Metodos Se analizaron de manera retrospectiva las manifestaciones clinicas, los hallazgos en las neuroimagenes, los metodos de diagnostico, las caracteristicas histologicas, la deteccion del ADN del virus de Epstein-Barr (VEB) por reaccion en cadena de la polimerasa (PCR) en liquido cefalorraquideo (LCR) y tejido cerebral y la evolucion de 18 pacientes con sida y linfomas primarios del sistema nervioso central (LPSNC). Resultados La incidencia global de LPSNC fue de 2,6%; 15 eran varones, con una edad media de 33,6 anos. Las manifestaciones clinicas mas comunes fueron los deficit neurologicos focales y las convulsiones. La media de linfocitos T CD4†fue de 44 cel./μl. Los LPSNC se presentaron como lesiones grandes y unicas en 14 pacientes (77,8%). Todas presentaron efecto de masa y edema perilesional. La deteccion del ADN del VEB en biopsias de tejido cerebral fue positiva en 9 pacientes. En siete de estos 9 casos, ademas, se detecto el ADN del VEB por PCR en muestras de LCR. La mediana de supervivencia luego del diagnostico fue de 75 dias. Conclusiones Este estudio confirma la asociacion entre el VEB y estos tumores. Los LPSNC se asociaron con mal pronostico y corta supervivencia en este grupo de pacientes.

HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV–HIV co-infected haemophilic patients with undetectable HCV viraemia

Summary.  Hepatitis C viraemia, in 38 human immunodeficiency virus positive (HIV+)/hepatitis C virus positive (HCV+) patients, was determined in haemophilic patients during the 4 years since initiation of highly active antiretroviral therapy (HAART). Six of 38 patients had persistently HCV‐negative viraemia for more than 2 years. No correlation between HCV‐negative viraemia and CD4+ T‐cell counts, HIV viral load, age, type or severity of haemophilia could be established. Reduced levels of HIV viral load and the immune reconstitution that follows the initiation of HAART were not enough to explain the disappearance of HCV from plasma. Individuals who cleared plasma HCV had significantly higher CD8+ T‐cell counts (P = 0.0013) (mean ± SE: 1153 ± 117.8cells μL−1) than those with HCV‐positive viraemia (819.1 ± 40.72 cells μL−1). Because HCV could maintain a low replication level in peripheral blood mononuclear cells (PBMC), we cultured PBMC of five of six patients with undetectable HCV viraemia. We found four of five HCV RNA‐positive cultures. The presence of HCV RNA in our cultures proved that these cells may be an important viral reservoir that could contribute to HCV recurrence in plasma even after long periods of negative viraemia. In summary, our results indicate that in spite of prolonged HCV‐negative plasma viraemia, HCV patients that are co‐infected with HIV may harbour replication‐competent HCV in their PBMC. Therefore, true clearance of HCV infection is difficult to achieve in these patients.

Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1

Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus‐infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV‐monoinfected and 25 HIV/HCV‐coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010‐2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed‐genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38–15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC‐associated variants persisted for 10 years in some subjects, emphasizing their role as long‐term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV‐infected patients.