HCV: is mission accomplished? The pros
Supplement : Abstracts of the 2016 International Symposium on HIV and Emerging Infectious Diseases (ISHEID)
Journal of Virus Eradication 2016; 2 supplement 1Abstract No : S2
Author(s):
Stanislas Pol
Cochin Hospital, Paris, France
Abstract :
An average of 150 million people are chronically infected by Hepatitis C virus (HCV) worldwide resulting in significant morbidity and mortality (500.000 to 1.4 million yearly), related to hepatic and extra-hepatic manifestations. The sustained virologic response (SVR), which corresponds to a complete recovery and is allowed by antiviral treatments, significantly reduces both morbidity (hepatocellular carcinoma, liver transplantation) and hepatic as well as extra-hepatic mortality. The overall mortality in those patients achieving SVR was reduced by 75%, especially in cirrhotic patients but also in HIV/HCV co-infected patients receiving interferon-including regimen and the occurrence of hepatocellular carcinoma at 5 years of follow-up dropped from 15 to 5% and need of liver transplantation from 10 to 1.2%, respectively in a recent meta-analysis. In a prospective French study of more than 1300 HCV-infected patients with biopsy-proven cirrhosis (the Cirvir ANRS CO12 cohort), at 3 or 5 years of post-treatment follow-up a significant decrease in the occurrence of hepatocellular carcinoma, of bacterial spontaneous peritoneal infection or other cirrhosis complications was reported in cirrhotic patients achieving SVR but also a 50% decrease in the occurrence of vascular disease (cardio- or cerebro-vascular disease). All these data, in line with registry studies, underline the need of achieving SVR in most if not all the HCV-infected patients, which means a large screening, an improvement of access to care of infected patients and of therapies.
The combination of pegylated interferon alfa and ribavirin (PR) which led to a sustained virologic response in around 45% of patients with HCV genotype (GT)1, 65% with HCV GT4, 70% with HCV GT3 and around 85% with HCV GT2 which was the standard of care for two decades. It has been replaced from 2011 to 2013 by a combination with PR and first-generation NS3/4A protease inhibitors (Telaprevir or Boceprevir) in GT 1-infected patients, allowing around 70% of SVR with a reduction of the duration of therapy from 48 to 24 weeks in half of treated patients. These first-generation regimens unexpectedly disappeared in 2014 with the rapid availability of interferon-free regimens combining different direct-acting antiviral drugs (DAAs). These DAAs target the main viral proteins involved in the replication cycle of HCV and combine NS3/4A protease inhibitors (Simeprevir or Paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (Sofosbuvir) and non nucleos(t)idic (Dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (Daclatasvir, Ledipasvir, Elbasvir, Velpatasvir). This therapeutic revolution combines 2 or 3 second wave DAAs, with or without ribavirin (RBV) but without interferon. The combinations are given for 8 to 24 weeks, according to baseline factors including fibrosis stage, GT and subtype, baseline viral load, prior therapeutic history of the patient (naïve or experienced) and pre-existing resistance-associated substitutions (RASs) and reach SVR rates greater than 90% with a good tolerance. The SVR rates (and the safety) are similar in the clinical trials and in the real-life, usually higher than 95% in per-protocol analysis.
The costs (which will be markedly reduced with the generic drugs), the risk of rare severe adverse events (<1% in “priority” patients) and the risk of resistance-associated substitutions (around 4%) are the unique and rare limitations for considering the access to cure in HCV-infected patients.