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.