Mortality among patients with cleared hepatitis C virus infection compared to the general population: a Danish nationwide cohort study

Abstract

Background: The increased mortality in HCV-infected individuals partly stems from viral damage to the liver and partly from risk-taking behaviours. We examined mortality in patients who cleared their HCV-infection, comparing it to that of the general population. We also addressed the question whether prognosis differed according to age, substance abuse (alcohol abuse and injection drug use) and comorbidity.

Methodology/principal findings: Patients with cleared HCV-infection were categorized into one of 8 groups according to age (20-39 years or 40-69 years) and patient characteristics (no substance abuse/no comorbidity; substance abuse/no comorbidity; no substance abuse/comorbidity; and substance abuse/comorbidity). For each patient, 4 age- and gender-matched individuals without substance abuse or comorbidity were selected from the general population, comprising a total of 8 comparison cohorts. We analyzed 10-year survival and used stratified Cox Regression analysis to compute mortality rate ratios (MRRs), comparing mortality between the 8 patient groups and the comparison cohorts, adjusting for personal income. Among patients without substance abuse or comorbidity, those aged 40-69 years had the same mortality as the comparison cohort (10-year survival: 95% (95% confidence interval [CI]: 93%-97%), MRR: 1.3 (95% CI: 0.8-2.3)), whereas those aged 20-39 years had higher mortality than the comparison cohort (10-year survival: 93% versus 99%, MRR: 5.7 (95% CI: 2.3-14.0). For both age categories, substance abuse and comorbidity decreased survival and increased MRRs. Patients aged 40-69 years with substance abuse and comorbidity suffered from substantial mortality (MRR: 12.5 (95% CI: 5.1-30.6)).

Conclusions: Mortality in patients aged 40-69 years with cleared HCV-infection is comparable to individuals without HCV, provided they have no substance abuse or comorbidity. Any substance abuse and/or comorbidity not captured in the registries used for our study could explain the increased mortality in patients aged 20-39 years without documented substance abuse or comorbidity.

Figure 1. Kaplan-Meier survival plot illustrating cumulative survival in patients with cleared HCV-infection and in an age- and gender-matched comparison cohort without comorbidity, alcohol abuse or IDU, according to age at study inclusion.

Solid line: Patients with cleared HCV-infection; broken line: Individuals from the comparison cohort. The left-hand graph illustrates survival among individuals aged 20–39 years at study inclusion. The right-hand graph illustrates survival in those aged 40–69 years at study inclusion.

Figure 2. Kaplan-Meier survival plots illustrating cumulative survival in patients with cleared HCV-infection and in an age- and gender-matched comparison cohort without comorbidity, alcohol abuse or IDU, according to patient characteristics and age at study inclusion.

Solid line: Patients with cleared HCV-infection; broken line: Individuals from the comparison cohort. The left-hand graphs illustrate survival in individuals aged 20–39 years at study inclusion; the right-hand graphs illustrate survival in those aged 40–69 years at inclusion. Top row: Patients with no substance abuse (alcohol abuse or IDU) or comorbidity; second row: patients with substance abuse; third row: patients with comorbidity; and last row: patients with substance abuse and comorbidity.

Figure 3. Cumulative incidence function illustrating cause-specific mortality in patients with cleared HCV-infection and an age- and gender-matched comparison cohort without comorbidity, alcohol abuse or IDU, according to age at study inclusion.

Solid line: Patients with cleared HCV-infection; broken line: Individuals from the comparison cohort. The left-hand graph illustrates survival in individuals aged 20–39 years at study inclusion; the right-hand graph illustrates survival in those aged 40–69 years at inclusion.

Figure 4. Cumulative incidence function illustrating cause-specific mortality in patients with cleared HCV-infection without comorbidity, alcohol abuse or IDU and an age- and gender-matched comparison cohort without comorbidity, alcohol abuse or IDU, according to age at study inclusion.

Solid line: Patients with cleared HCV-infection; broken line: Individuals from the comparison cohort. Left- hand graph illustrates survival in individuals aged 20–39 years at study inclusion; right-hand graph illustrates survival in those aged 40–69 years at inclusion.