Mechanism relevant to hepatocellular carcinoma occurrence after negative conversion of viral DNA in treatment of chronic hepatitis B patients with nucleos(t)ide drugs / 中华肝脏病杂志

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and most of the patients have a background of chronic HBV infection. Nucleos(t)ide drugs (NAs) are currently recommended by major guidelines as a first-line treatments for chronic hepatitis B. However, it is still clinically possible to observe that some patients who have acquired virological response (HBV DNA below the lower detection limit) after NAS treatment progress to HCC, and its mechanism of development is still unclear. In this review, the mechanism relevant to HCC progression in treatment of chronic hepatitis B patients with NAs is analyzed mainly from the aspects of gene integration and persistent inflammatory injury.

Updates on human equilibrative nucleoside transporter 1 in neoplastic diseases / 国际儿科学杂志

The human equilibrative nucleoside transporter 1(hENT1)is a multi-integrated membrane protein that mediates the transport of nucleosides, nucleobases and nucleoside analogs.It is mainly distributed on the cell membrane in humans.hENT1 maintains the homeostasis of cells and the intracellular concentration of nucleoside drugs through facilitating diffusion, thereby affecting DNA and RNA synthesis, cell signaling, metabolic regulation and tumor chemotherapy.This article reviews the progress in the structure and function of hENT1, the distribution in tumor tissues, the nucleoside analogs response and the prognosis of neoplastic diseases.

Updates on human equilibrative nucleoside transporter 1 in neoplastic diseases / 国际儿科学杂志

The human equilibrative nucleoside transporter 1 (hENT1) is a multi-integrated membrane protein that mediates the transport of nucleosides,nucleobases and nucleoside analogs.It is mainly distributed on the cell membrane in humans.hENT1 maintains the homeostasis of cells and the intracellular concentration of nucleoside drugs through facilitating diffusion,thereby affecting DNA and RNA synthesis,cell signaling,metabolic regulation and rumor chemotherapy.This article reviews the progress in the structure and function of hENT1,the distribution in tumor tissues,the nucleoside analogs response and the prognosis of neoplastic diseases.

In vitro comparison of acyclovir, ganciclovir and cidofovir against equid alphaherpesvirus 3 and evaluation of their efficacy against six field isolates / Comparación in vitro de aciclovir, ganciclovir y cidofovir contra alfa-herpesvirus equino 3 y evaluación de la eficacia de los mismos frente a 6 aislamientos de campo del virus

Equid alphaherpesvirus 3 (EHV3) is the etiological agent of equine coital exanthema (ECE), which is a venereal, highly contagious disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genitalia of mares and stallions. EHV3 remains in a latent state after a successful infection and there are latently infected animals in which the virus is reactivated and generally re-excreted subclinically. There are no available vaccines for this condition and prevention is based on the clinical examination of mares prior to mating, which allows to segregate those showing clinical signs. As this approach does not eliminate the risk of contagion in stallions from subclinically infected mares, there is a need for a specific EHV3 treatment. Nowadays, there exist various antiviral compounds of proven effectiveness for other alphaherpesviruses affecting humans and animals. The aim of the present study was to compare the efficacy of three antiviral compounds, acyclovir, ganciclovir and cidofovir against EHV3 in vitro, and to assess their efficacy against six EHV3 Argentinian field isolates. To determine the efficacy of these compounds in vitro, three parameters were analyzed: reduction of plaque number, reduction of plaque size and reduction of viral production. Additionally, the effectiveness of the three compounds at an optimum concentration previously determined in this study was investigated for the EHV3 field isolates. Based on our results, ganciclovir was the most potent antiviral compound to reduce EHV3 replication in vitro and may thus be a valuable candidate for treatment and prevention of ECE in mares and stallions.

El alfa-herpesvirus equino 3 (EHV3) es el agente etiológico del exantema coital equino (ECE), enfermedad venérea, altamente contagiosa y caracterizada por la aparición de pápulas, vesículas, pústulas y úlceras en los genitales externos de yeguas y padrillos. Luego de la primo-infección, el EHV3 se mantiene en el animal en un estado de latencia a partir del cual puede reactivar y excretarse, generalmente de manera subclínica. No existen vacunas, por lo que la prevención se basa en la detección de las lesiones clínicas previo al servicio, y la segregación de estos animales. Sin embargo, este abordaje no previene la infección del padrillo por parte de yeguas que excretan el virus de manera subclínica, y por lo tanto existe la necesidad de un tratamiento específico contra el EHV3. En la actualidad, existen varios compuestos antivirales de probada eficacia contra herpesvirus humanos y veterinarios. El objetivo de este trabajo es comparar la eficacia de 3 compuestos antivirales, aciclovir, ganciclovir y cidofovir, contra EHV3 in vitro, y evaluar la eficacia de los mismos contra 6 cepas de campo argentinas de EHV3. Para determinar la eficacia de los compuestos in vitro se evaluaron 3 parámetros: reducción del número de placas de lisis, reducción del tamaño de placas de lisis y reducción de la producción de virus. Adicionalmente, la efectividad de los compuestos en una concentración óptima, previamente determinada en este estudio, fue determinada para 6 cepas de campo argentinas de EHV3. De acuerdo con los resultados obtenidos, ganciclovir fue el compuesto más potente en reducir la replicación del EHV3 in vitro, y por lo tanto podría considerarse un potencial candidato para el tratamiento y la prevención del ECE en yeguas y padrillos.

Avaliação da resposta terapêutica de pacientes em tratamento para hepatite B crônica em hospital de referência para doenças hepáticas / Evaluation of the therapeutic response of patients in treatment for chronic hepatitis B in a hospital of reference for liver diseases

Objetivo: descrever as respostas bioquímica, sorológica e virológica à terapêutica em pacientes com hepatite B crônica em um hospital de referência para doenças hepáticas. Método: estudo transversal, analítico, onde foram coletados dados de 25 pacientes com hepatite B crônica tratados com interferon ?-2a 5MU/dia, lamivudina 100mg/dia, entecavir 1mg/dia e adefovir dipivoxil 10mg/dia. Estes pacientes foram atendidos no Ambulatório do Grupo do Fígado da Fundação Santa Casa de Misericórdia do Pará, no período de agosto de 2000 a dezembro de 2008. Os pacientes foram distribuídos em 2 grupos: HBeAg positivos e HBeAg negativos. Consideraram-se como respostas, a normalização de ALT, negativação do VHB-DNA por PCR, para os grupos de HBeAg positivos e negativos; e soroconversão HBeAg/anti-HBe, para o grupo HBeAg positivo. Resultados: observou-se que no grupo dos pacientes HBeAg positivos, houve soroconversão HBeAg/anti-HBe em 53,3%. Houve normalização de ALT em 68%, onde 44% pertencia ao grupo HBeAg positivo e 24% ao grupo HBeAg negativo. A negativação do VHB-DNA ocorreu em 68% dos pacientes, sendo 40% do grupo HBeAg positivo e 28% do grupo HBeAg negativo. Conclusão: todos os pacientes tratados com entecavir e adefovir, embora numa pequena casuística, apresentaram resposta bioquímica, sorológica e virológica. Aqueles tratados com interferon também apresentaram bons resultados. Porém, os que foram tratados com lamivudina, embora maior parte tenha apresentado resposta bioquímica e virológica favoráveis, tiveram respostas inferiores em relação aos demais esquemas terapêuticos avaliados nesta pesquisa.

Objective: to describe the therapeutic response biochemical, serologic and virologic in patients with chronic hepatitis B in a reference hospital for liver diseases. Method: cross-sectional study, analytical, where data were collected from 25 patients with chronic hepatitis B treated with interferon ?-2a 5MU/day, lamivudine 100 mg/day, entecavir 1mg/day and adefovir dipivoxil 10 mg/day. These patients were treated at the Clinic of the Liver´s Group of the Fundação Santa Casa de Misericórdia do Pará, from August 2000 to December 2008. The patients were divided into 2 groups: HBeAg-positive and HBeAg-negative. It is considered as responses, the normalization of ALT levels and undetectable HBV-DNA levels by PCR, for the groups of positive and negative HBeAg; and seroconversion HBeAg/anti-HBe, for the HBeAg-positive group. Results: it was observed that in the patients' group HBeAg-positive, there were seroconversion HBeAg/anti-HBe in 53,3%. There was normalization of ALT levels in 68%, while 44% belonged to the HBeAg positive and 24% of HBeAg negative group. Non-detectability of HBV-DNA by PCR ocurred in 68% of the patients, being 40% of the HBeAg-positive group and 28% of the HBeAg-negative group. Conclusion:. concluded that all the patients treated with entecavir and adefovir, although in a small casuistry, achieved biochemical, serologic and virologic responses. Those treated with standard interferon also showed good results. However, those who were treated with lamivudine, although larger part has obtained biochemical and virologic favorable response, they had lower results in relation to the other drugs evaluated in this study