Reply to: “Cost-effectiveness of upcoming treatments for hepatitis C: We need to get the models right”
Authors: Zobair M. Younossi, Linda Henry, Mendel Singer
Journal: Journal of Hepatology (2014)

Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patientsJournal of HepatologyVol. 60Issue 3PreviewHepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75–80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens. Full-Text PDF Cost-effectiveness of upcoming treatments for hepatitis C: We need to get the models rightJournal of HepatologyVol. 61Issue 2PreviewWe read with great interest the recent article on cost-effectiveness of current and future treatments of patients with HCV genotype 1 by Younossi and colleagues [1]. Although the authors explore a very pertinent issue regarding treatment decisions in such patients, there are certain aspects that somewhat decrease the validity of their findings. Full-Text PDF Open Access Interferon free regimens for treatment of chronic hepatitis C genotype 1 patients lead to better clinical and cost outcomesTo the Editor:We appreciate the input from Tshochatzis et al. in their letter to the editor about our recently published article [[1]Younossi Z.M. Singer M.E. Mir H.M. Henry L. Hunt S. Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.J Hepatol. 2014; 60 ([Epub 2013 Nov 19]): 530-537https://doi.org/10.1016/j.jhep.2013.11.009Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar]. One of the issues raised has to do with differences in health-related quality of life (HRQL) related to the stage of fibrosis. Although there is evidence to suggest that patients with advanced liver disease have more impairment of HRQL, there is absolutely no credible evidence to suggest that HRQL impairment is different between earlier histologic stages of fibrosis [2Björnsson E. Verbaan H. Oksanen A. Frydén A. Johansson J. Friberg S. et al.Health-related quality of life in patients with different stages of liver disease induced by hepatitis C.Scand J Gastroenterol. 2009; 44: 878-887https://doi.org/10.1080/00365520902898135Crossref PubMed Scopus (51) Google Scholar, 3Younossi Z. Boparai N. Price L. Kiwi M.L. McCormick M. Guyatt G. Health-related quality of life in chronic liver disease: the impact of type and severity of disease.Am J Gastroenterol. 2001; 96: 2199-2205https://doi.org/10.1111/j.1572-0241.2001.03956.xCrossref PubMed Google Scholar]. On the other hand, we do agree that when patients have cirrhosis, especially those with decompensated cirrhosis, their HRQL is significantly more impaired and this was considered in our analysis. As for the disutility of oral regimen, we used actual data obtained from patients who were treated in clinical trials [[4]Younossi Z.M. Stepanova M. Cure S. Bourrhis F. Nader F. Hunt S. Estimating health status using EQ5D for chronic hepatitis c patients treated with sofosbuvir containing regimens.J Hepatol. 2014; 60: S30Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar] and did conduct sensitivity analysis (the online supplementary document provides additional details of sensitivity analyses). Therefore, we believe that our HRQL assumptions for our economic analysis were correct.We also understand that our analysis was performed using efficacy data for all oral regimens from abstracts presented in international meetings. At the time, this was all the data that was available. Nevertheless, fully published data from all oral regimens suggest even higher SVR-12 rates than what we considered in our model [5Afdhal N. Reddy R. Nelson D. Lawitz E. Gordon S. Schiff E. et al.Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med. 2014; 370: 1483-1493https://doi.org/10.1056/NEJMoa1316366Crossref PubMed Scopus (1155) Google Scholar, 6Feld J. Kowdley K. Coakley E. Sigal S. Nelson D. Crawford D. et al.Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.N Engl J Med. 2014; 370: 1594-1603https://doi.org/10.1056/NEJMoa1315722Crossref PubMed Scopus (732) Google Scholar]. In fact, we believe that our study may have actually underestimated the cost effectiveness of all oral regimens which should further strengthen our conclusions.As far as the staging of liver disease by Fibroscan® is concerned, our initial analysis was performed using the “gold standard” for staging which is liver biopsy. In fact, this approach yielded very similar results to those of Fibroscan. It is also important to note that while Fibroscan® is widely used in Europe, despite FDA approval, Fibroscan® is still not widely used or available in the United States. Part of the problem is large scale validation data using Fibroscan® in population with high prevalence of visceral obesity is lacking and this may affect the performance of this technology. Nevertheless, our sensitivity analysis showed that even when the cost of staging (Fibroscan® or liver biopsy) was free and with perfect sensitivity and specificity, treating all with an oral regimen remained cost-effective by conservative standards (less than $50,000/QALY).It is true that the mean improvement in life expectancy from treating all for oral therapy is 1.8 months from treating an extra 17%. It would be wrong, however, to characterize that as “marginal” since that improvement is not spread evenly over the whole population but is gained entirely in the population at risk of progression to advanced liver disease. Thus, about 10% of these extra people treated are prevented from advanced liver disease and gain over 8 years of life.Finally, we have used an exhaustive approach to obtain all the data for the model, including extensive review of the literature, previously published models, and expert reviews of our assumptions. We believe that the assumptions used in our models are quite robust and our conclusions remain valid.Conflict of interestThe authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. Interferon free regimens for treatment of chronic hepatitis C genotype 1 patients lead to better clinical and cost outcomesTo the Editor:We appreciate the input from Tshochatzis et al. in their letter to the editor about our recently published article [[1]Younossi Z.M. Singer M.E. Mir H.M. Henry L. Hunt S. Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.J Hepatol. 2014; 60 ([Epub 2013 Nov 19]): 530-537https://doi.org/10.1016/j.jhep.2013.11.009Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar]. One of the issues raised has to do with differences in health-related quality of life (HRQL) related to the stage of fibrosis. Although there is evidence to suggest that patients with advanced liver disease have more impairment of HRQL, there is absolutely no credible evidence to suggest that HRQL impairment is different between earlier histologic stages of fibrosis [2Björnsson E. Verbaan H. Oksanen A. Frydén A. Johansson J. Friberg S. et al.Health-related quality of life in patients with different stages of liver disease induced by hepatitis C.Scand J Gastroenterol. 2009; 44: 878-887https://doi.org/10.1080/00365520902898135Crossref PubMed Scopus (51) Google Scholar, 3Younossi Z. Boparai N. Price L. Kiwi M.L. McCormick M. Guyatt G. Health-related quality of life in chronic liver disease: the impact of type and severity of disease.Am J Gastroenterol. 2001; 96: 2199-2205https://doi.org/10.1111/j.1572-0241.2001.03956.xCrossref PubMed Google Scholar]. On the other hand, we do agree that when patients have cirrhosis, especially those with decompensated cirrhosis, their HRQL is significantly more impaired and this was considered in our analysis. As for the disutility of oral regimen, we used actual data obtained from patients who were treated in clinical trials [[4]Younossi Z.M. Stepanova M. Cure S. Bourrhis F. Nader F. Hunt S. Estimating health status using EQ5D for chronic hepatitis c patients treated with sofosbuvir containing regimens.J Hepatol. 2014; 60: S30Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar] and did conduct sensitivity analysis (the online supplementary document provides additional details of sensitivity analyses). Therefore, we believe that our HRQL assumptions for our economic analysis were correct.We also understand that our analysis was performed using efficacy data for all oral regimens from abstracts presented in international meetings. At the time, this was all the data that was available. Nevertheless, fully published data from all oral regimens suggest even higher SVR-12 rates than what we considered in our model [5Afdhal N. Reddy R. Nelson D. Lawitz E. Gordon S. Schiff E. et al.Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med. 2014; 370: 1483-1493https://doi.org/10.1056/NEJMoa1316366Crossref PubMed Scopus (1155) Google Scholar, 6Feld J. Kowdley K. Coakley E. Sigal S. Nelson D. Crawford D. et al.Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.N Engl J Med. 2014; 370: 1594-1603https://doi.org/10.1056/NEJMoa1315722Crossref PubMed Scopus (732) Google Scholar]. In fact, we believe that our study may have actually underestimated the cost effectiveness of all oral regimens which should further strengthen our conclusions.As far as the staging of liver disease by Fibroscan® is concerned, our initial analysis was performed using the “gold standard” for staging which is liver biopsy. In fact, this approach yielded very similar results to those of Fibroscan. It is also important to note that while Fibroscan® is widely used in Europe, despite FDA approval, Fibroscan® is still not widely used or available in the United States. Part of the problem is large scale validation data using Fibroscan® in population with high prevalence of visceral obesity is lacking and this may affect the performance of this technology. Nevertheless, our sensitivity analysis showed that even when the cost of staging (Fibroscan® or liver biopsy) was free and with perfect sensitivity and specificity, treating all with an oral regimen remained cost-effective by conservative standards (less than $50,000/QALY).It is true that the mean improvement in life expectancy from treating all for oral therapy is 1.8 months from treating an extra 17%. It would be wrong, however, to characterize that as “marginal” since that improvement is not spread evenly over the whole population but is gained entirely in the population at risk of progression to advanced liver disease. Thus, about 10% of these extra people treated are prevented from advanced liver disease and gain over 8 years of life.Finally, we have used an exhaustive approach to obtain all the data for the model, including extensive review of the literature, previously published models, and expert reviews of our assumptions. We believe that the assumptions used in our models are quite robust and our conclusions remain valid. To the Editor: We appreciate the input from Tshochatzis et al. in their letter to the editor about our recently published article [[1]Younossi Z.M. Singer M.E. Mir H.M. Henry L. Hunt S. Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.J Hepatol. 2014; 60 ([Epub 2013 Nov 19]): 530-537https://doi.org/10.1016/j.jhep.2013.11.009Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar]. One of the issues raised has to do with differences in health-related quality of life (HRQL) related to the stage of fibrosis. Although there is evidence to suggest that patients with advanced liver disease have more impairment of HRQL, there is absolutely no credible evidence to suggest that HRQL impairment is different between earlier histologic stages of fibrosis [2Björnsson E. Verbaan H. Oksanen A. Frydén A. Johansson J. Friberg S. et al.Health-related quality of life in patients with different stages of liver disease induced by hepatitis C.Scand J Gastroenterol. 2009; 44: 878-887https://doi.org/10.1080/00365520902898135Crossref PubMed Scopus (51) Google Scholar, 3Younossi Z. Boparai N. Price L. Kiwi M.L. McCormick M. Guyatt G. Health-related quality of life in chronic liver disease: the impact of type and severity of disease.Am J Gastroenterol. 2001; 96: 2199-2205https://doi.org/10.1111/j.1572-0241.2001.03956.xCrossref PubMed Google Scholar]. On the other hand, we do agree that when patients have cirrhosis, especially those with decompensated cirrhosis, their HRQL is significantly more impaired and this was considered in our analysis. As for the disutility of oral regimen, we used actual data obtained from patients who were treated in clinical trials [[4]Younossi Z.M. Stepanova M. Cure S. Bourrhis F. Nader F. Hunt S. Estimating health status using EQ5D for chronic hepatitis c patients treated with sofosbuvir containing regimens.J Hepatol. 2014; 60: S30Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar] and did conduct sensitivity analysis (the online supplementary document provides additional details of sensitivity analyses). Therefore, we believe that our HRQL assumptions for our economic analysis were correct. We also understand that our analysis was performed using efficacy data for all oral regimens from abstracts presented in international meetings. At the time, this was all the data that was available. Nevertheless, fully published data from all oral regimens suggest even higher SVR-12 rates than what we considered in our model [5Afdhal N. Reddy R. Nelson D. Lawitz E. Gordon S. Schiff E. et al.Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med. 2014; 370: 1483-1493https://doi.org/10.1056/NEJMoa1316366Crossref PubMed Scopus (1155) Google Scholar, 6Feld J. Kowdley K. Coakley E. Sigal S. Nelson D. Crawford D. et al.Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.N Engl J Med. 2014; 370: 1594-1603https://doi.org/10.1056/NEJMoa1315722Crossref PubMed Scopus (732) Google Scholar]. In fact, we believe that our study may have actually underestimated the cost effectiveness of all oral regimens which should further strengthen our conclusions. As far as the staging of liver disease by Fibroscan® is concerned, our initial analysis was performed using the “gold standard” for staging which is liver biopsy. In fact, this approach yielded very similar results to those of Fibroscan. It is also important to note that while Fibroscan® is widely used in Europe, despite FDA approval, Fibroscan® is still not widely used or available in the United States. Part of the problem is large scale validation data using Fibroscan® in population with high prevalence of visceral obesity is lacking and this may affect the performance of this technology. Nevertheless, our sensitivity analysis showed that even when the cost of staging (Fibroscan® or liver biopsy) was free and with perfect sensitivity and specificity, treating all with an oral regimen remained cost-effective by conservative standards (less than $50,000/QALY). It is true that the mean improvement in life expectancy from treating all for oral therapy is 1.8 months from treating an extra 17%. It would be wrong, however, to characterize that as “marginal” since that improvement is not spread evenly over the whole population but is gained entirely in the population at risk of progression to advanced liver disease. Thus, about 10% of these extra people treated are prevented from advanced liver disease and gain over 8 years of life. Finally, we have used an exhaustive approach to obtain all the data for the model, including extensive review of the literature, previously published models, and expert reviews of our assumptions. We believe that the assumptions used in our models are quite robust and our conclusions remain valid. Conflict of interestThe authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.