The new hepatitis C virus bottleneck: Can delaying therapy be justified?

C hronic hepatitis C (CHC) infection is one of the most common causes of chronic liver disease worldwide and the leading indication for liver transplantation. In the United States, CHC afflicts more than 3.2 million people, resulting in cirrhosis, hepatic decompensation, hepatocellular carcinoma, and death. Although the incidence of hepatitis C viral (HCV) infection is declining in the United States, the incidence of cirrhosis is rising; and the number of deaths related to CHC is not projected to peak until 2030. Successful eradication of HCV remains a priority and is associated with clear reductions in all-cause and liver-related outcomes, as well as alleviation of symptoms, improved quality of life, and the prevention of person-to-person transmission. The regulatory approval of second-generation direct-acting antiviral medications marked an extraordinary turning point in HCV therapeutics. The once-daily oral nucleotide polymerase inhibitor sofosbuvir and the once-daily protease inhibitor simeprevir were each heralded as medical breakthroughs. They were soon followed by other agents, including all-oral combination regimens comprised of sofosbuvir and ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir with or without ribavirin. With these regimens, it became possible to offer patients safe and effective (sustained virological response rates exceeding 90% in most populations) alternatives to interferon and ribavirin– based therapy. These regimens have an excellent safety profile and proven effectiveness across many genotypes, regardless of prior treatment failure or degree of underlying fibrosis. With their release comes the hope that we might one day witness the worldwide eradication of HCV. Enthusiasm for these medications, however, has been dampened by the reality of their high costs, a major obstacle to their delivery. Twelve weeks of treatment costs $84,000 for sofosbuvir, $66,360 for simeprevir, $94,500 for sofosbuvir and ledipasvir, and $83,320 for paritaprevir/ritonavir/ombitasvir/dasabuvir. Recent studies have collectively indicated that for genotype 1 these direct-acting antiviral agent–based regimens are costeffective, and recent discounting efforts promise to make them even more cost-effective. However, cost effectiveness and cost are not the same thing. As a result of these treatments now being applied to so many persons over so brief a period, there has been a significant shortterm budgetary strain. It was recently reported that Medicare Part D spending on HCV regimens exceeded $4.5 billion in 2014, more than 15 times the $286 million spent in 2013. Overall, 2014 saw a 13.1% rise in prescription drug spending, and it has been estimated that total health care expenditures related to HCV therapy could soon reach $27 billion per year. Saddled by skyrocketing prescription costs, many state-funded Medicaid programs and private insurance payers have responded by restricting access to directacting antiviral agent–based regimens to those with advanced (Metavir F3 or F4) fibrosis or severe extrahepatic manifestations. Others have gone further; in Texas, Medicaid has elected not to cover sofosbuvir at all. Are these restrictions justified? It is possible, if there exists an equally effective alternative therapy for a particular condition, at a less expensive price. However, this is not the case for HCV, particularly for those patients who are intolerant of or not candidates for interferon and ribavirin–based treatment. Furthermore, restricting allocation implies that certain patients would derive greater benefit from treatment than others and that the choice to delay therapy will not place a patient at undue risk of harm. While persons with advanced fibrosis are clearly at highest risk for short-term complications, it is not clear that persons with lesser degrees of fibrosis are not at risk for harm. The true cost of delaying HCV treatment is not well understood. It has been shown that disease progression in CHC is nonlinear, and recent analysis of the Department of Veterans Affairs database has demonstrated that rates of fibrosis progression may be far more accelerated than previously thought. Thus, any decision to defer or delay treatment runs the risk of allowing a subset of patients to progress to cirrhosis and thereby Abbreviations: CHC, chronic hepatitis C; HCV, hepatitis C virus. Received June 1, 2015; accepted June 2, 2015. Address reprint requests to: Raymond T. Chung, Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. E-mail: rtchung@partners.org Copyright VC 2015 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27931 Potential conflict of interest: Dr. Chung received grants from Gilead, AbbVie, Bristol-Myers Squibb, Merck, and MassBiologics.