Towards a more complete understanding of the association between a hepatitis C sustained viral response and cause-specific outcomes

Hamish A. Innes (Lead / Corresponding author), Scott A. McDonald, John F. Dillon, Sam Allen, Peter C. Hayes, David Goldberg, Peter R. Mills, Stephen T. Barclay, David Wilks, Heather Valerio, Ray Fox, Diptendu Bhattacharyya, Nicholas Kennedy, Judith Morris, Andrew Fraser, Adrian J. Stanley, Peter Bramley, Sharon J. Hutchinson

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    Abstract

    Sustained viral response (SVR) is the optimal outcome of hepatitis C virus (HCV), yet more detailed data is 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 3385 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 three-fold: 1) Overall, SVR is associated with reduced hazard for a range of hepatic and non-hepatic events; 2) an association between SVR and behavioural events is consistent with SVR patients leading healthier lives; 3) the short-term value of SVR is greatest for those with nonmild disease.

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    Original languageEnglish
    Pages (from-to)355-364
    Number of pages10
    JournalHepatology
    Volume62
    Issue number2
    Early online date25 Mar 2015
    DOIs
    Publication statusPublished - Aug 2015

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    Innes, H. A., McDonald, S. A., Dillon, J. F., Allen, S., Hayes, P. C., Goldberg, D., Mills, P. R., Barclay, S. T., Wilks, D., Valerio, H., Fox, R., Bhattacharyya, D., Kennedy, N., Morris, J., Fraser, A., Stanley, A. J., Bramley, P., & Hutchinson, S. J. (2015). Towards a more complete understanding of the association between a hepatitis C sustained viral response and cause-specific outcomes. Hepatology, 62(2), 355-364. https://doi.org/10.1002/hep.27766