Experiencia en práctica clínica real con los nuevos antivirales de acción directa en hepatitis crónica C / Experience in real clinical practice with new direct acting antivirals in chronic hepatitis C

Introducción y objetivo: La inclusión en práctica real de los antivirales de acción directa en pacientes con hepatitis crónica por VHC ha supuesto un hito histórico en Medicina. Pacientes y métodos: Estudio analítico, prospectivo que incluyó 126 pacientes con hepatitis crónica por VHC tratados con antivirales de acción directa. Evaluamos la eficacia y seguridad del tratamiento y factores asociados a fracaso terapéutico. Resultados: Edad 54±10 años. Varón (70%). Cirrosis (60%). Distribución según genotipos: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B y C (n=15). Naïve (56%). Tasa RVS fue (87,3%): Child-A (91%), Child-B (75%) y Child-C (60%). Las mejores tasas de curación se alcanzaron con las combinaciones Combo 3D/2D±ribavirina (RVS=97,4%; n=39) y sofosbuvir/ledipasvir±ribavirina (RVS=93,1%; n=29). Tasas<90% se registraron con: sofosbuvir+simeprevir±ribavirina (RVS=88%; n=25), simeprevir+daclatasvir±ribavirina (RVS=78%; n=18) y sofosbuvir+daclatasvir±ribavirina (RVS=73,3%; n=15). La adicción de ribavirina a estas 3 últimas opciones terapéuticas (n=19) mejoraba las tasas de curación (RVS=94,7%; 18/19) frente a su ausencia (n=39; RVS=77%). Mejoría MELD (40%). Salida lista trasplante (20%). Sustituciones asociadas a resistencias NS3: G1a (posiciones 80K; n=5); G1b y G4 (posición 168 y 36; n=4), mientras para NS5a: G1a (posición 30; n=2) y G1b y G3 (posición 93; n=3). Variables asociadas al fracaso en análisis multivariante (p<0,05): presencia de ascitis, G3 y dosis de ribavirina<600mg/día. Discusión: La presencia de genotipo 3, ascitis o dosis de ribavirina<600mg/día se asoció a mayores tasas de fracasos. Sería recomendable el uso de ribavirina≥600mg/día en cirróticos G1 o G3, que vayan a ser tratados con sofosbuvir+simeprevir o daclatasvir, si no hubiese disponibilidad de un test de resistencia basal (AU)

Introduction and objective: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. Patients and methods: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. Results: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. Discussion: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available (AU)

Experience in real clinical practice with new direct acting antivirals in chronic hepatitis C. / Experiencia en práctica clínica real con los nuevos antivirales de acción directa en hepatitis crónica C.

INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. RESULTS: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. DISCUSSION: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available.

[Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis C]. / Cinética lipídica en el tratamiento antiviral dual en pacientes con hepatitis crónica C.

BACKGROUND AND OBJECTIVE: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). PATIENTS AND METHODS: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different "degrees of lipid requirement" that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve "a favorable lipid metabolism" (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. RESULTS: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P<.05, these differences being more significant for genotype IL-28B-CC (P=.013). Patients with sustained virological response had higher rates of FLM. CONCLUSIONS: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins.