[Measurement of hepatitis C virus RNA 12 weeks after treatment predicts sustained virological response in HIV-HCV co-infected patients]. / La valoración de RNA del virus de la hepatitis C realizada a las 12 semanas de finalizar el tratamiento predice la respuesta virológica sostenida en enfermos con coinfección por VIH y VHC.

OBJECTIVE: The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients. PATIENTS AND METHODS: HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml). RESULTS: Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%). CONCLUSION: Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response.

Liver fibrosis, host genetic and hepatitis C virus related parameters as predictive factors of response to therapy against hepatitis C virus in HIV/HCV coinfected patients.

OBJECTIVE: To establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism). PATIENTS AND METHODS: A sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, -238 TNF-α and -592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count. RESULTS: Patients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600,000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600,000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of -238 TNF-α genotype GG was detected in patients with significant liver fibrosis. CONCLUSIONS: In HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a -238 TNF-α polymorphism in these patients.

Influence of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Interleukin 10 Genes on the Risk of Liver Cirrhosis in HIV-HCV Coinfected Patients.

OBJECTIVE: Analysis of the contribution of genetic (single nucleotide polymorphisms (SNP) at position -238 and -308 of the tumor necrosis factor alpha (TNF-α) and -592 of the interleukin-10 (IL-10) promotor genes) and of classical factors (age, alcohol, immunodepression, antirretroviral therapy) on the risk of liver cirrhosis in human immunodeficiency (HIV)-hepatitis C (HCV) virus coinfected patients. PATIENTS AND METHODS: Ninety one HIV-HCV coinfected patients (50 of them with chronic hepatitis and 41 with liver cirrhosis) and 55 healthy controls were studied. Demographic, risk factors for the HIV-HCV infection, HIV-related (CD4+ T cell count, antiretroviral therapy, HIV viral load) and HCV-related (serum ALT concentration, HCV viral load, HCV genotype) characteristics and polymorphisms at position -238 and -308 of the tumor necrosis factor alfa (TNF- α) and -592 of the interleukin-10 (IL-10) promotor genes were studied. RESULTS: Evolution time of the infection was 21 years in both patients' groups (chronic hepatitis and liver cirrhosis). The group of patients with liver cirrhosis shows a lower CD4+ T cell count at the inclusion in the study (but not at diagnosis of HIV infection), a higher percentage of individuals with previous alcohol abuse, and a higher proportion of patients with the genotype GG at position -238 of the TNF-α promotor gene; polymorphism at -592 of the IL-10 promotor gene approaches to statistical significance. Serum concentrations of profibrogenic transforming growth factor beta1 were significantly higher in healthy controls with genotype GG at -238 TNF-α promotor gene. The linear regression analysis demonstrates that the genotype GG at -238 TNF-α promotor gene was the independent factor associated to liver cirrhosis. CONCLUSION: It is stressed the importance of immunogenetic factors (TNF-α polymorphism at -238 position), above other factors previously accepted (age, gender, alcohol, immunodepression), on the evolution to liver cirrhosis among HIV-infected patients with established chronic HCV infections.

La valoración de RNA del virus de la hepatitis C realizada a las 12 semanas de finalizar el tratamiento predice la respuesta virológica sostenida en enfermos con coinfección por VIH y VHC / Measurement of hepatitis C virus RNA 12 weeks after treatment predicts sustained virological response in HIV-HCV co-infected patients

Objetivo El objetivo de este estudio fue evaluar si la determinación de RNA del virus de la hepatitis C (VHC-RNA) a las 12 semanas tras la finalización del tratamiento podía predecir la respuesta viral sostenida al tratamiento anti-VHC (interferón pegilado alfa-2a y ribavirina) en enfermos coinfectados por el virus de la inmunodeficiencia humana (VIH).Enfermos y métodos Fueron incluidos los pacientes coinfectados por VIH y VHC que completaron un curso completo de tratamiento anti-VHC y que fueron evaluados a las semanas +12 y +24 tras la finalización del tratamiento para determinación del HCV-RNA sérico (RealTime HCV (Abbott, Wiesbaden, Alemania) (límite inferior de detección, 12 U/ml).Resultados Cuarenta de los 66 enfermos tratados (61%) presentaron una respuesta al final del tratamiento. Se les realizó una valoración a las 12 y 24 semanas tras el fin de la terapia. El VHC-RNA sérico fue indetectable en 28 de ellos a la semana +12, y el 100% de ellos permaneció indetectable a la semana +24 (el patrón de referencia de respuesta viral sostenida). El valor predictivo positivo fue 100% (intervalo de confianza al 95% 98,21-100%).Conclusión La evaluación posterior al tratamiento de la hepatitis crónica C en enfermos coinfectados por VIH para detectar la presencia de recaída virológica puede ser realizada a la semana +12, en lugar de a la semana +24, proporcionando así una nueva definición de respuesta virológica sostenida (AU)

Objective The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients. Patients and methods HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml).Results Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%).Conclusion Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response (AU)