Abstract
BACKGROUND:Chronic hepatitis C (CHC) infection is a major global health problem, affecting 71 million individuals worldwide and causing half a million deaths a year from cirrhosis and liver cancer. Treatment for CHC can result in a sustained viral response (SVR), which is considered to be a hepatitis C “cure”.However, treatment is not a panacea: firstly, it can be financially costly; and secondly it can entail significant adverse effects. Because of these drawbacks, it is important that the benefits of achieving SVR are clearly understood and articulated to policy makers. Thus, the goal of this thesis was to assess the association between an SVR and the onward risk of mortality and serious morbidity.
METHODS:
We conducted a series of epidemiological studies using secondary data from Scotland, Denmark and the United States. These studies, inter alia, compared: A) cause-specific mortality and hospital admission rates for treated patients achieving SVR versus treated patients not achieving SVR; B) cause-specific mortality rates for individuals with diagnosed CHC versus individuals with diagnosed spontaneous resolved infection; C) cause-specific mortality rates for patients achieving SVR versus the general population; and D) all-cause mortality rates for individuals with CHC versus individuals without CHC in a community (i.e. general population) setting. We used our findings from these comparisons to determine, via mathematical modelling, the expected benefit of an SVR: 1) for the individual patient, in terms of additional years of life lived and additional years of life lived free of cirrhosis and liver cancer; and (2) for the overall population, in terms of transmission of hepatitis C infection, and the number of new patients presenting with serious liver morbidity.
RESULTS:
From comparison A, the 7.5 year absolute risk reduction (ARR) for liver mortality associated with SVR (vs. non-SVR) was 3.0% (95% Cl: 1.5%-4.5%) following adjustment for relevant confounders. The ARR depended strongly on initial fibrosis stage however- i.e. among individuals with significant/advanced fibrosis, the ARR was 6.3%, whereas for individuals no/minimal fibrosis the ARR was 0.0% (p-value for difference<0.001). Comparisons B-D all indicate that the excess morbidity/mortality in the CHC infected population is not entirely due to CHC per se. For instance,comparison C demonstrates that “cured” SVR patients still die at twice the rate of the general population, and health risk behaviours (HRBs) are the major determinant of this heightened mortality risk. Our mathematical models confirmed the strong heterogeneity in prognosis according to fibrosis stage. For instance, the probability that a 45 year old individual will benefit from SVR in terms of living longer is 6.3% (95% CE3.5-9.6) if mild fibrosis is present, versus 49.3% (95% Cl: 36.7-60.9) if advanced fibrosis is present. Mathematical modelling to forecast the population impact of distinct treatment strategies in Scotland indicates that prioritising treatment in people who inject drugs could potentially reduce incident infection to negligible levels by 2025. Alternatively, prioritising individuals with more advanced liver fibrosis could reverse and stabilise the number of persons newly developing severe liver morbidity by 2023.
CONCLUSION:
This thesis curates a range of novel epidemiological comparisons that yield new insight into the valueof a hepatitis C SVR in a resource-rich setting. At the individual-level, we demonstrate that SVR isassociated with considerable reductions in mortality risk for those with moderate/advanced fibrosis.Prioritising treatment in this patient group will reverse the rise in numbers of infected individualsdeveloping severe liver morbidity, but likely at the cost of reducing HCV transmission (i.e. thenumber of people newly acquiring CHC infection) to negligible levels before the year 2025. Thesedata also strongly caution that the impact of SVR on high excess mortality will be partial unless HRBsare addressed alongside provision of antiviral therapy.
| Date of Award | 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Sharon Hutchinson (Supervisor) |