Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C / The Value Of Genetics In The Era Of Hepatitis C Triple Therapy

A pesar de la introducción de los inhibidores de la proteasa (IP) en el tratamiento de la hepatitis C, la sensibilidad al IFN continúa siendo fundamental para alcanzar la respuesta virológica (RVS) y erradicar la infección viral. En la actualidad, el interferón pegilado (IFNpeg) y la ribavirina (RBV) son necesarios para evitar la selección de mutantes resistentes a los IP. La probabilidad de obtener la RVS con biterapia en pacientes naives infectados con genotipo 1 varía entre el 40-50%. Es decir, en casi la mitad de este grupo de pacientes no sería preciso introducir un IP, evitando así los efectos adversos del mismo y disminuyendo considerablemente el coste del tratamiento. Identificar a estos potenciales respondedores a la doble terapia es uno de los mayores retos en la práctica clínica. La variabilidad genética del huésped constituye uno de los factores fundamentales en la sensibilidad al IFNpeg y, por tanto, en la respuesta al tratamiento actual. Otros factores basales relacionados con el huésped, con el virus y, sobre todo, los factores intratratamiento como la respuesta virológica rápida (RVR), se relacionan fuertemente con la probabilidad de alcanzar la RVS. La evidencia sobre la decisión de tratar con doble o triple terapia en función de los factores predictores de respuesta se basa en estudios retrospectivos o análisis posthoc de los estudios pivotales de los IP. El estudio de los polimorfismos del gen de IFNL3 (IL28B), ITPA, genes estimulados por IFN (ISG), TT/ΔG (ss469415590; IFNL4) y de transportadores de RBV son factores genéticos importantes que nos pueden ayudar a tomar la decisión de tratar con doble o triple terapia en pacientes naives

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients

[The value of genetics in the era of hepatitis C triple therapy]. / Valor de la genética en la era de la terapia triple frente al virus de la hepatitis C.

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.

Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.