title: Real-world effectiveness and predictors of sustained virological response with all-oral therapy in 21,242 hepatitis C genotype-1 patients.
abstract: BACKGROUND
  Predictors of sustained virological response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. We evaluated effectiveness and identified predictors of SVR for ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ±RBV) and ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ±RBV in patients treated in routine practice.
  
  
  METHODS
  Observational, intent-to-treat cohort of 21,142 genotype-1 patients initiating 8 or 12 weeks of LDV/SOF ±RBV or 12 weeks of OPrD ±RBV at any Veterans Affairs facility. Multivariate logistic regression models were constructed to model SVR and identify predictors.
  
  
  RESULTS
  SVR was 91.2% (9,781/10,720) for LDV/SOF, 89.6% (3,266/3,646) for LDV/SOF+RBV, 91.7% (1,197/1,306) for OPrD and 87.8% (3,365/3,832) for OPrD+RBV. For LDV/SOF ±RBV, reduced odds of SVR occurred in African-Americans (0.80, 95% CI 0.70, 0.92, P<0.001), body mass index (BMI)<25 (0.77, 95% CI 0.66, 0.90, P<0.001), BMI≥30 (0.77, 95% CI 0.67, 0.89, P<0.001), proton pump inhibitors (PPIs; 0.81, 95% CI 0.71, 0.92, P<0.001), decompensated liver disease (0.58, 95% CI 0.45, 0.74, P<0.001) and FIB4>3.25 (0.60, 95% CI 0.53, 0.69, P<0.001). For OPrD ±RBV, FIB-4>3.25 negatively predicted SVR (0.72, 95% CI 0.59, 0.88, P<0.001). Detectable 4-week on-treatment HCV RNA≥15 IU/ml reduced SVR odds for both regimens (LDV/SOF ±RBV OR 0.49, 95% CI 0.41, 0.58, P<0.001; OPrD ±RBV OR 0.38, 95% CI 0.29, 0.50, P<0.001). Receipt of OPrD+RBV compared to LDV/SOF reduced odds of SVR (OR 0.70, 95% CI 0.62, 0.80, P<0.001). Mental health diagnosis did not impact likelihood of SVR.
  
  
  CONCLUSIONS
  The diversity and size of this cohort allowed for extensive examination of regimen-specific predictors of SVR. FIB-4>3.25 and detectable 4-week on-treatment HCV RNA had the greatest negative impact. African-American race, low or high BMI, and PPIs negatively impacted odds of SVR for LDV/SOF ±RBV. Mental health diagnoses did not.
authors.affiliation: Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Lisa I
authors.initials: LI
authors.lastname: Backus
authors.affiliation: Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Belperio
authors.affiliation: Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Shahoumian
authors.affiliation: Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Loomis
authors.affiliation: Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Mole
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D000072230:Sustained Virologic Response; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents