[Interferon in hepatitis B]. / Interferón en la hepatitis B.

Hepatitis B virus (HBV) infection is a worldwide public health problem. There are an estimated 350 million persons with chronic HBV infection that could progress to cirrhosis and hepatocarcinoma with nearly one million deaths per year. In the last few years the therapeutic options in chronic hepatitis B have increased and currently six treatments are authorized: standard interferon (IFN)-alpha, pegylated interferon-alpha (PEG-IFNalpha), lamivudine, adefovir, entecavir, and telbivudine. For the last 25 years, conventional IFNalpha has been used as the treatment of chronic hepatitis B (CHB) and currently PEG-IFNalpha is indicated due to its greater effectiveness. Both drugs are first line options for HBeAg(+) and HBeAg(-) CHB. The advantages of IFNalpha and PEG-IFNalpha are that these drugs are administered for a limited time period, they achieve a higher sustained response rate and do not induce HBV mutants with antiviral resistance. These drugs achieve greater HBeAG and HBsAG clearance due to their antiviral and immunomodulatory activity. PEG-IFNalpha induces sustained biochemical and virological response in approximately one third of patients with HBeAg(+) CHB. The best response to IFNalpha and PEG-IFNalpha is obtained in patients with elevated transaminase levels, moderate viral load and HBV genotypes A and B. The disadvantages of IFNalpha and PEG-IFNalpha are their adverse effects and contraindications. These drugs cannot be administered in patients with decompensated cirrhosis. The combination of nucleos(t)ide analogs with PEG-IFNalpha could achieve much higher sustained response rates; however, which treatment constitutes the most suitable therapeutic strategy requires investigation.

Interferón en la hepatitis B / Interferon in hepatitis B

La infección por el virus de la hepatitis B (VHB) es un problema de salud pública mundial. Se estima que hay en el mundo 350 millones de personas infectadas crónicamente por el VHB que pueden evolucionar a cirrosis y hepatocarcinoma, con cerca de un millón de muertes anuales. En los últimos años, las opciones terapéuticas de la hepatitis B crónica (HBC) han aumentado y en la actualidad se dispone de 6 tratamientos autorizados: interferón alfa (IFNα) estándar, interferón pegilado alfa (PEG-IFNα), lamivudina, adefovir, entecavir y telbivudina. Desde hace 25 años se ha utilizado el IFNα convencional como tratamiento de la HBC y actualmente se indica el PEG-IFNα por ser más eficaz. Ambos constituyen opciones terapéuticas de primera línea para la HBC AgHBe positivo y AgHBe negativo. Las ventajas del IFNα y PEG-IFNα son su administración con duración definida en el tiempo, consiguen mayor tasa de respuesta sostenida y no inducen mutantes del VHB con resistencia antiviral. Consiguen mayor aclaramiento de AgHBe y AgHBs debido a su acción antiviral e inmunomoduladora. El PEG-IFNα induce una respuesta sostenida bioquímica y virológica en alrededor de un tercio de los pacientes con HBC AgHBe positivo. Responden mejor al IFNα y PEG-IFNα los pacientes que tienen transaminasas elevadas, carga viral moderada y los genotipos A y B del VHB. El IFNα y el PEG-IFNα tienen el inconveniente de ser fármacos con efectos secundarios y contraindicaciones. No se pueden administrar a pacientes con cirrosis descompensada. La combinación de análogos de nucleóstidos/nucleótidos con PEG-IFNα podría conseguir tasas de respuesta sostenida más elevadas, pero debe investigarse qué estrategia terapéutica es la más adecuada

Hepatitis B virus (HBV) infection is a worldwide public health problem. There are an estimated 350 million persons with chronic HBV infection that could progress to cirrhosis and hepatocarcinoma with nearly one million deaths per year. In the last few years the therapeutic options in chronic hepatitis B have increased and currently six treatments are authorized: standard interferon (IFN)-α, pegylated interferon-α (PEG-IFNα), lamivudine, adefovir, entecavir, and telbivudine. For the last 25 years, conventional IFNα has been used as the treatment of chronic hepatitis B (CHB) and currently PEG-IFNα is indicated due to its greater effectiveness. Both drugs are first line options for HBeAg(+) and HBeAg(-) CHB. The advantages of IFNα and PEG-IFNα are that these drugs are administered for a limited time period, they achieve a higher sustained response rate and do not induce HBV mutants with antiviral resistance. These drugs achieve greater HBeAG and HBsAG clearance due to their antiviral and immunomodulatory activity. PEG-IFNα induces sustained biochemical and virological response in approximately one third of patients with HBeAg(+) CHB. The best response to IFNα and PEG-IFNα is obtained in patients with elevated transaminase levels, moderate viral load and HBV genotypes A and B. The disadvantages of IFNα and PEG-IFNα are their adverse effects and contraindications. These drugs cannot be administered in patients with decompensated cirrhosis. The combination of nucleos(t)ide analogs with PEG-IFNα could achieve much higher sustained response rates; however, which treatment constitutes the most suitable therapeutic strategy requires investigation

Interferón en la hepatitis B / Interferon in hepatitis B

La infección por el virus de la hepatitis B (VHB) es un problema de salud pública mundial. Se estima que hay en el mundo 350 millones de personas infectadas crónicamente por el VHB que pueden evolucionar a cirrosis y hepatocarcinoma, con cerca de un millón de muertes anuales. En los últimos años, las opciones terapéuticas de la hepatitis B crónica (HBC) han aumentado y en la actualidad se dispone de 6 tratamientos autorizados: interferón alfa (IFNα) estándar, interferón pegilado alfa (PEG-IFNα), lamivudina, adefovir, entecavir y telbivudina. Desde hace 25 años se ha utilizado el IFNα convencional como tratamiento de la HBC y actualmente se indica el PEG-IFNα por ser más eficaz. Ambos constituyen opciones terapéuticas de primera línea para la HBC AgHBe positivo y AgHBe negativo. Las ventajas del IFNα y PEG-IFNα son su administración con duración definida en el tiempo, consiguen mayor tasa de respuesta sostenida y no inducen mutantes del VHB con resistencia antiviral. Consiguen mayor aclaramiento de AgHBe y AgHBs debido a su acción antiviral e inmunomoduladora. El PEG-IFNα induce una respuesta sostenida bioquímica y virológica en alrededor de un tercio de los pacientes con HBC AgHBe positivo. Responden mejor al IFNα y PEG-IFNα los pacientes que tienen transaminasas elevadas, carga viral moderada y los genotipos A y B del VHB. El IFNα y el PEG-IFNα tienen el inconveniente de ser fármacos con efectos secundarios y contraindicaciones. No se pueden administrar a pacientes con cirrosis descompensada. La combinación de análogos de nucleóstidos/nucleótidos con PEG-IFNα podría conseguir tasas de respuesta sostenida más elevadas, pero debe investigarse qué estrategia terapéutica es la más adecuada(AU)

Hepatitis B virus (HBV) infection is a worldwide public health problem. There are an estimated 350 million persons with chronic HBV infection that could progress to cirrhosis and hepatocarcinoma with nearly one million deaths per year. In the last few years the therapeutic options in chronic hepatitis B have increased and currently six treatments are authorized: standard interferon (IFN)-α, pegylated interferon-α (PEG-IFNα), lamivudine, adefovir, entecavir, and telbivudine. For the last 25 years, conventional IFNα has been used as the treatment of chronic hepatitis B (CHB) and currently PEG-IFNα is indicated due to its greater effectiveness. Both drugs are first line options for HBeAg(+) and HBeAg(-) CHB. The advantages of IFNα and PEG-IFNα are that these drugs are administered for a limited time period, they achieve a higher sustained response rate and do not induce HBV mutants with antiviral resistance. These drugs achieve greater HBeAG and HBsAG clearance due to their antiviral and immunomodulatory activity. PEG-IFNα induces sustained biochemical and virological response in approximately one third of patients with HBeAg(+) CHB. The best response to IFNα and PEG-IFNα is obtained in patients with elevated transaminase levels, moderate viral load and HBV genotypes A and B. The disadvantages of IFNα and PEG-IFNα are their adverse effects and contraindications. These drugs cannot be administered in patients with decompensated cirrhosis. The combination of nucleos(t)ide analogs with PEG-IFNα could achieve much higher sustained response rates; however, which treatment constitutes the most suitable therapeutic strategy requires investigation(AU)

The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection.

BACKGROUND/AIMS: CXCR3 and CCR5 play a major role in recruiting cytotoxic T cells (Tc) and secreting secondary type 1 cytokines (Tc1) in the liver. HCV could impair their expression as a survival mechanism. The role of these chemokine receptors on CD8+ cells in chronic hepatitis C is analysed. METHODS: Serum, chemokines, peripheral blood and intrahepatic lymphocytes from chronic hepatitis C patients were studied. CXCR3/CCR5 expressing CD8+ cells were quantified by flow-cytometry. Serum chemokines concentration (CXCL10/CCL3) was measured by ELISA. Basal data were correlated with liver inflammation. Longitudinal data were obtained during treatment and correlated with virologic response. RESULTS: CCR5/CXCR3 expressing CD8+ cells were enriched in the liver and correlated with inflammation. Chronic HCV patients presented the same frequency of CCR5(high)/CXCR3(high) expressing CD8+ cells in peripheral blood as in healthy controls but higher serum concentration of CXCL10/CCL3. Treatment with PEG-interferon alpha-2b plus ribavirin increased CCR5(high)/CXCR3(high) expressing CD8+ cells frequency in peripheral blood and decreased CXCL10/CCL3 serum concentration. Increase in CXCR3(high) expressing CD8+ cells after 24 weeks of treatment was correlated with SVR. CONCLUSIONS: In chronic hepatitis C, anti-viral treatment induces an increase in CD8+ cells expressing chemokine receptors associated with Tc1 response and a reduction in their ligands. Achievement of viral control is associated with an increase in CXCR3(high) expressing CD8+ cells during treatment.