Letters Screening for hepatitis C

Authors’ reply to Foster and colleagues

BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1000 (Published 24 February 2015) Cite this as: BMJ 2015;350:h1000
  1. Ronald L Koretz, emeritus professor of clinical medicine1,
  2. Kenneth W Lin, associate professor of family medicine2,
  3. John P A Ioannidis, professor of medicine3,
  4. Jeanne Lenzer, medical investigative journalist4
  1. 1David Geffen-UCLA School of Medicine, CA, USA
  2. 2Georgetown University School of Medicine, Washington, DC, USA
  3. 3Stanford University, CA, USA
  4. 4New York, USA
  1. jeanne.lenzer{at}gmail.com

We thank Foster and colleagues for their comments.1 2 Projections of disease progression that are based on natural history studies from tertiary referral centres may exaggerate hepatitis C virus (HCV) related morbidity and mortality. Inception cohort and epidemiological data suggest that only a minority of infected people will progress to end stage liver disease over their lifetime.1

Foster and colleagues repeatedly asserted that treatment is effective, but the cited evidence cannot show this.3 4 5 Van der Meer summarised seven studies that compared treated patients with non-randomised untreated ones or compared treated patients who did or did not achieve a sustained virological response (SVR).3 Neither study design can establish efficacy because of confounding variables or the absence of an untreated comparator group. Kraus and colleagues compared patients who did or did not achieve an SVR in an unblinded study that measured a subjective outcome.4 Another study described only a correlation between two unvalidated surrogate outcomes.5

Moreover, even if treatment is shown to be effective and cost effective, we would still need to know if the additional screening costs of cohort screening (a lower proportion of screened people would be positive), including labelling, would be acceptable.

The observed association between HCV and extrahepatic diseases (such as diabetes, dyslipidaemia, neurocognitive disorders, and non-hepatic mortality) does not prove causation or imply that antiviral treatment can prevent or improve these conditions.

There is no evidence that people with HCV identified through cohort based screening will make lifestyle changes to reduce disease transmission—a question that could also be answered by our proposed trial.

We did not claim that cancer development rates were the same in those who achieved an SVR as in untreated people. We used the observation that each year 1% of patients with severe fibrosis and an SVR still developed cancer only to point out that SVRs were not necessarily cures and that this rate was at the low end of the natural history data for untreated patients with cirrhosis.6

We do not know if SVRs are valid surrogate outcomes. We do know that some patients with an SVR will not be cured and that many others never needed treatment. If treatment is not beneficial, any adverse events are unacceptable.

We believe that the policy advocated by Foster and colleagues should rest on convincing evidence; such evidence does not currently exist.


Cite this as: BMJ 2015;350:h1000



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