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The science, economics, and effectiveness of combination therapy for hepatitis C
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Editor,—No one affected by hepatitis C virus (HCV) will question Professor Dusheiko's insistence on the importance of effective therapy standards for HCV and the funding to meet them (OpenUrlFREE Full Text). With research and clinical evidence pointing to a prevalence of HCV infection far in excess of human immunodeficiency virus (HIV),1 the issue has now become urgent. Patients and clinicians alike will await the forthcoming NICE appraisal in the hope it recommends in favour of allocating sufficient resources to cover treatment costs for those most in need and best able to benefit.

However, while a positive response will be welcome it will also uncover issues that have still to be fully addressed. These centre on who will/should be selected for treatment and the effects of the treatment itself.

Regarding the first issue there remains a debate around who will benefit most from treatment. The tendency is to assess outcome in terms of genotyping, age, duration of viraemia, extent of liver damage, and other complicating factors, such as continued drug and alcohol abuse. While there may be some validity to such categorisations, they are not at all absolute and can demoralise patients. Nevertheless, and leaving such considerations aside, if HCV infection is as widespread as some clinicians anticipate, it would be unrealistic to assume that funding will be available to treat everyone. This means that some form of treatment selection will need to be adopted. Should this occur, the question remains as to how clinicians will make choices and what criteria they will use. Furthermore, will protocols be in place to govern these criteria to ensure they are standardised nationwide?

Although Dusheiko et al cite the potential priority given by the NHS to combination treatment as the salient issue, this needs to be addressed in conjunction with the equally important matter of who should receive this treatment. Whether patients are offered standard combination therapy, combination therapy with pegylated interferon (PEG IFN), or PEG IFN alone is in some ways secondary to the issue of who is actually going to be given treatment. Will it be based on disease progression or expected response to treatment, or both?

Before considering this further, a factor that needs to be implicated in discussions around HCV, but which clinicians tend to underestimate, is patient tolerance and possible lingering effects of therapy. Although there seems to be a fairly clear cut case in favour of the greater efficacy of combination treatment, it is harder for patients to tolerate than monotherapy with IFN, particularly when taken over 48 weeks. Dusheiko et al state that the 20% (approximately) of patients who discontinue therapy before 48 weeks usually do so because of “insomnia, depression, irritability, or anaemia”. This would seem to be a minimising of the extent and intensity of side effects from combination therapy, which can be equally as debilitating for some patients as those of chemotherapy. In addition, the sequelae of treatment can sometimes linger for months following its cessation.

Given the potential severity of side effects, many patients with mild HCV have resisted conventional treatment methods and opted instead to try to minimise disease progression by recourse to alternative therapies. A recent nationwide trial offered to patients with mild HCV failed to recruit anywhere near its target numbers. This would seem to imply that those with less risk of progressive disease, and therefore less motivation to seek a cure, are more resistant to therapeutic intervention.

Notwithstanding the obvious factor of the greater and more urgent need of treatment for patients with progressive disease following HCV infection, perhaps this trend in mild HCV sufferers might offer some insight as to how patients sometimes choose for themselves, suggesting to those involved with the healthcare of HCV patients an indicator of how best to prioritise treatment should such selection prove necessary.


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