Impact of hepatitis C virus eradication on hepatocellular carcinogenesis

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. Infection with the hepatitis C virus (HCV) represents one of the most common risk factors for HCC development and cases of HCV-related complications have been rising over the last two decades. Though the standard of HCV therapy has been interferon (IFN)-based for many years, the therapeutic revolution spurred by the development of direct-acting antivirals (DAAs) promises to usher in a new era in which chronic hepatitis C becomes a rare disease. Based on long term follow-up in persons experiencing IFN-based sustained virologic responses (SVR), we can expect that rates of HCV-associated HCC will decrease significantly after the widespread adoption of DAAs, but there remains a persistent risk for HCC even among some patients with advanced fibrosis who have achieved SVR. As such, individuals treated for HCV with advanced fibrosis should continue to be screened regularly for HCC post-SVR. Furthermore, as the population of patients with SVR grows, it will become imperative to accurately identify those individuals at high-risk for developing HCC, appropriately allocate resources for screening, and consider cost-effective chemopreventive strategies. Risk factors include pre-existing advanced fibrosis/cirrhosis, older age, diabetes mellitus, and ethanol use. Additionally, laboratory biomarkers and genetic signatures are currently being identified that not only predict the likelihood of HCC development in SVR patients but may also serve as dynamic indicators of therapeutic response.

Direct‐acting antiviral drugs and hepatitis C virus: A therapeutic revolution?

“…1 We agree that the high upfront costs of direct-acting antivirals have proved to be a major challenge for payers. However, a number of independent studies have demonstrated that all-oral DAA regimens, even at their wholesale prices, are cost-effective under most circumstances.…”

“…1 First, there is a very substantial cost and hope cannot replace postmarketing studies. For example, sofosbuvir, which costs approximately $1000 per day and $84,000 for the full 12-week treatment, will increase the Medicare Part D Prescription Drug Benefit by $6.5 billion in 2015, an overall 8% increase in spending.…”

Reply to antiviral therapy and hepatocellular carcinogenesis

“…We appreciate the interest of Testino et al in our recent review 1 . We agree that the risk of hepatocellular carcinoma (HCC) remains elevated in patients who achieve sustained virologic response (SVR), particularly in those who already have cirrhosis.…”

Untitled

“…26 It is important to note that despite the decrease in HCC risk in patients achieving a sustained virologic response, patients with advanced liver fibrosis still remain at long-term risk for HCC. 27 This means that patients with HCV infection will require continuous monitoring, and future studies will need to validate any decrease in the incidence of HCC.…”