Alimentary Pharmacology and Therapeutics Invited Commentaries This joint effort by clinicians, stakeholders and drug companies can provide significant benefits as several analyses based on Markov models have shown that a 75% increase in the number of patients treated with a regimen achieving a 75% SVR rate will reduce liver-related deaths in the US by a staggering 57% in 2030.5, 6
ACKNOWLEDGEMENT Declaration of personal interests: A. Aghemo has received grant and research support from Roche and Gilead Sciences. Speaking and teaching: Roche, Janssen, Merck. P. Lampertico has been on the advisory board and speaking bureau for BMS, Roche, Gilead Sciences, GSK and Merck. Declaration of funding interests: None.
Commentary: absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C – authors’ reply A. H. Talal*, J. LaFleur†, R. S. Hoop‡, P. Pandya§, P. Martin¶, I. M. Jacobson**, J. Han‡ & E. J. Korner‡ *State University of New York, Buffalo, NY, USA. † University of Utah, Salt Lake City, UT, USA. ‡ Genentech, South San Francisco, CA,USA. § Kansas City VA Medical Center, Kansas City, MO, USA. ¶ University of Miami, Miami, FL, USA. **Weill Cornell Medical College, New York, NY, USA. E-mail:
[email protected] doi:10.1111/apt.12424
We thank Drs Aghemo and Lampertico for their commentary on our work.1, 2 We agree that the investigation provides evidence to support the notion that medical contraindications to interferon (IFN) and ribavirin are not the major obstacles to low rates of hepatitis C virus (HCV) treatment initiation when using IFN-based therapies. However, we disagree with the hypothesis that ‘introduction of IFN-free regimens will only increase the number of anti-HCV treatment eligible patients by 10– 15%’ for a few reasons. First, our sample was derived from the general US population, which historically has had a much lower 554
REFERENCES 1. Talal AH, Lafleur J, Hoop R, et al. Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: results from a US database of over 45 000 HCV-infected, evaluated patients. Aliment Pharmacol Ther 2013; 37: 473–81. 2. Lettmeier B, M€ uhlberger N, Schwarzer R, et al. Market uptake of new antiviral drugs for the treatment of hepatitis C. J Hepatol 2008; 49: 528–36. 3. Sarrazin C, Hezode C, Zeuzem S, et al. Antiviral strategies in hepatitis C virus infection. J Hepatol 2012; 56(Suppl. 1): S88–100. 4. Aghemo A, Lampertico P, Colombo M. Assessing long-term treatment efficacy in chronic hepatitis B and C: between evidence and common sense. J Hepatol 2012; 57: 1326–35. 5. Volk ML, Tocco R, Saini S, et al. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology 2009; 50: 1750–5. 6. Davis GL, Alter MJ, El-Serag H, et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 2010; 138: 513–21.
rate of HCV infection in comparison with that found among specific groups, such as veterans and persons who inject drugs. Indeed, HCV infection was only identified in 0.5% of patients in our data set,2 a percentage well below the US national average of 2%.3 Secondly, rates of medical comorbidities that are contraindications to IFN-based therapy, such as mental health issues, have been shown to be much higher in these population subgroups.4 Thirdly, a variety of other reasons at the patient, provider and institutional levels have historically played a larger role as reasons for aversion to initiate IFN-based therapy than have medical contraindications. Some of these items, for example, patients’ fear of side effects attributable to IFN or former drug users’ concerns that medication administered by injection may foster relapse to injection drug use, factors that were not evaluated as part of our data set, will be significantly diminished if not entirely eliminated by removal of IFN from HCV therapeutic regimen. Others, such as expanded screening and HCV educational programmes, should improve with a multicomponent approach as outlined by Drs Aghemo and Lampertico.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 Aliment Pharmacol Ther 2013; 38: 549-558 ª 2013 John Wiley & Sons Ltd
Invited Commentaries REFERENCES 1. Aghemo A, Lampertico P. Commentary: absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C. Aliment Pharmacol Ther 2013; 38: 553–4. 2. Talal AH, Lafleur J, Hoop R, et al. Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: results from a US database of over 45 000 HCV-infected,
Commentary: predicting complicated Crohn’s disease and surgery – phenotypes, genetics, serology and psychological characteristics of a population-based cohort J. M. Benitez & E. Louis Department of Gastroenterology, University Hospital CHU of Liege, Liege, Belgium. E-mail:
[email protected] doi:10.1111/apt.12416
The prospective population-based study by Ryan et al.1 evaluated a combination of phenotypic, genetic, serologic, and psychological characteristics for the prediction of complicated Crohn’s disease (CD). Prediction of complicated CD is of great importance to allow selection of subgroups of patients who are candidates for an early intensive treatment regimen aimed at decreasing the risk of cumulative tissue damage and complications. Only ASCA IgG-positive serology was identified as an independent predictor of stricturing/penetrating behaviour and surgery at 9–10 years from diagnosis.1 When interpreting the results of such a study, a few key questions must be kept in mind. When were the serological markers measured? What was the added value of these markers over simple clinical characteristics? Was the size of the sample studied large enough to have the power to disclose relevant predictors? What is the potential predictive value and what is the relevance of the disclosed predictors? In the present study, the markers were not measured at diagnosis, but a median of 4.3 years after diagnosis. At that time point, 55% of the studied population had already developed stricturing or penetrating behaviour, and only a few more patients progressed on to this phenotype during the next 5 years. Thus, in the present Aliment Pharmacol Ther 2013; 38: 549-558 ª 2013 John Wiley & Sons Ltd
evaluated patients. Aliment Pharmacol Ther 2013; 37: 473– 81. 3. Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int 2011; 31: 1090–101. 4. Bini EJ, Brau N, Currie S, et al. Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection. Am J Gastroenterol 2005; 100: 1772–9.
study, as in previously published studies,2, 3 ASCA IgG-positive serology was more a reflection of, rather than a predictor of, complicated behaviour. Ileal location has been consistently associated with complicated behaviour, and both of these have been associated with surgery, particularly in population-based studies.4, 5 Yet, in the present study, these simple clinical characteristics were not introduced in the multivariate models to predict disease outcome. It remains thus to be proved that ASCA IgG (which are significantly associated with disease location and behaviour) has a significant added value in predicting outcome. Although initially population-based, the size of the studied cohort was finally rather small (n = 182) and would not allow the disclosure of risk factors with a relative risk 75% to be clinically meaningful. The relevance of the outcome studied may also be questioned. All types of surgeries should not be considered the same in CD: a 10-cm resection of the terminal ileum does not have the same significance as a subtotal colectomy or extensive small bowel resection. Despite these limitations, the authors must be commended for having performed such a study, assessing a broad range of potential risk factors in a population-based setting. The study of psychological variables was particularly original. Although these were generally not significantly associated with disease behaviour or surgery, the majority of the patients reported some level of adverse childhood experience (73%) and high childhood adversity impact tended to be more common in those who underwent surgery. As emphasised by the authors, this is something that will require further attention and research. 555
