title: Toward a more complete understanding of the association between a hepatitis C sustained viral response and cause-specific outcomes.
abstract: Sustained viral response (SVR) is the optimal outcome of hepatitis C virus (HCV) therapy, yet more detailed data are required to confirm its clinical value. Individuals receiving treatment in 1996-2011 were identified using the Scottish HCV clinical database. We sourced data on 10 clinical events: liver, nonliver, and all-cause mortality; first hospitalisation for severe liver morbidity (SLM); cardiovascular disease (CVD); respiratory disorders; neoplasms; alcohol-intoxication; drug intoxication; and violence-related injury (note: the latter three events were selected a priori to gauge ongoing chaotic lifestyle behaviours). We determined the association between SVR attainment and each outcome event, in terms of the relative hazard reduction and absolute risk reduction (ARR). We tested for an interaction between SVR and liver disease severity (mild vs. nonmild), defining mild disease as an aspartate aminotransferase-to-platelet ratio index (APRI) <0.7. Our cohort comprised 3,385 patients (mean age: 41.6 years), followed-up for a median 5.3 years (interquartile range: 3.3-8.2). SVR was associated with a reduced risk of liver mortality (adjusted hazard ratio [AHR]: 0.24; P < 0.001), nonliver mortality (AHR, 0.68; P = 0.026), all-cause mortality (AHR, 0.49; P < 0.001), SLM (AHR, 0.21; P < 0.001), CVD (AHR, 0.70; P = 0.001), alcohol intoxication (AHR, 0.52; P = 0.003), and violence-related injury (AHR, 0.51; P = 0.002). After 7.5 years, SVR was associated with significant ARRs for liver mortality, all-cause mortality, SLM, and CVD (each 3.0%-4.7%). However, we detected a strong interaction, in that ARRs were considerably higher for individuals with nonmild disease than for individuals with mild disease.
  
  
  CONCLUSIONS
  The conclusions are 3-fold: (1) Overall, SVR is associated with reduced hazard for a range of hepatic and nonhepatic events; (2) an association between SVR and behavioral events is consistent with SVR patients leading healthier lives; and (3) the short-term value of SVR is greatest for those with nonmild disease.
authors.affiliation: School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.|Health Protection Scotland, Glasgow, United Kingdom.
authors.forename: Hamish A
authors.initials: HA
authors.lastname: Innes
authors.affiliation: School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.|Health Protection Scotland, Glasgow, United Kingdom.
authors.forename: Scott A
authors.initials: SA
authors.lastname: McDonald
authors.affiliation: Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: John F
authors.initials: JF
authors.lastname: Dillon
authors.affiliation: University Hospital, Crosshouse, United Kingdom.
authors.forename: Sam
authors.initials: S
authors.lastname: Allen
authors.affiliation: Royal Infirmary Edinburgh, Edinburgh, United Kingdom.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.affiliation: School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.|Health Protection Scotland, Glasgow, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goldberg
authors.affiliation: Gartnavel General Hospital, Glasgow, United Kingdom.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mills
authors.affiliation: Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Barclay
authors.affiliation: Western General Hospital, Edinburgh, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Wilks
authors.affiliation: School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.|Health Protection Scotland, Glasgow, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: Valerio
authors.affiliation: The Brownlee Center, Glasgow, United Kingdom.
authors.forename: Ray
authors.initials: R
authors.lastname: Fox
authors.affiliation: Kirkcaldy Hospital, Fife, United Kingdom.
authors.forename: Diptendu
authors.initials: D
authors.lastname: Bhattacharyya
authors.affiliation: Monklands Hospital, Lanarkshire, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kennedy
authors.affiliation: Southern General Hospital, Glasgow, United Kingdom.
authors.forename: Judith
authors.initials: J
authors.lastname: Morris
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fraser
authors.affiliation: Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Stanley
authors.affiliation: Stirling Royal Infirmary, Stirling, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Bramley
authors.affiliation: School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom.|Health Protection Scotland, Glasgow, United Kingdom.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Hutchinson
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002423:Cause of Death; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000401:mortality / Q000503:physiopathology / Q000821:virology*; D017093:Liver Failure / Q000401:mortality / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D040242:Risk Reduction Behavior; D012720:Severity of Illness Index; D016019:Survival Analysis; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents