What is Killing People With Hepatitis C Virus Infection?

JasonGrebely, B.Sc., Ph.D.; Gregory J.Dore, M.B.B.S., Ph.D., F.R.A.C.P., M.P.H.

Disclosures

Semin Liver Dis. 2011;31(4):331-339. 

In This Article

The Potential Impact of Improving HCV Therapy on Mortality Rates

The burden of HCV-related advanced liver disease is projected to increase further in many countries.[9,10,11,12,13,14] A major public health issue is the potential impact of improving HCV therapy on these projected increases in mortality. In HIV, the availability of effective combination antiretroviral therapy from the mid-1990s dramatically reduced the overall mortality rate and altered the distribution of causes of death (increasing proportion of non-AIDS related deaths).[78–80] The lower overall disease-specific HCV mortality risk compared with HIV and more protracted disease progression (life expectancy for chronic HCV infection is on average reduced by several years rather than decades for HIV) mean that a more-effective and more broadly implemented therapeutic intervention will be unable to have the dramatic impact that was seen for antiretroviral therapy. However, there is considerable potential for improved HCV therapeutic intervention to alter expected HCV-related mortality, particularly when the temporal "ageing cohort" effect is most pronounced.

The recent introduction of DAA therapy in combination with PEG-IFN and ribavirin will enhance treatment response rates for those with chronic HCV genotype 1 infection and shorten duration of therapy for many patients.[1] However, low HCV treatment (PEG-IFN/ribavirin) uptake rates for those with chronic HCV genotype 2/3,[12,15–20] despite treatment success of 70 to 80% and shorter duration therapy (generally 24 weeks), suggest that initial DAA-based response rate improvements will have a modest impact at the population level. Recent evidence suggests that IFN-free combination DAA therapy with high rates of treatment response is feasible.[81] Improvements in DAA therapy tolerability and dosing schedules are highly likely given agents in phase II/III development.[1] Large population-level impacts on HCV-related liver disease mortality will likely require IFN-free combination therapy that is tolerable, has a favorable dosing schedule, and is effective over a relatively short duration. Such HCV therapeutic advances are within reach over the next decade.

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