Antiviral Agents Show Safety and Efficacy in Hard to Treat Patients with HCV Infection
Direct-acting antiviral agents against the hepatitis C virus (HCV) are proving to be effective in even the most difficult to treat patients—including those with chronic kidney disease, decompensated cirrhosis, and disease recurrence after transplantation.
Paul Pockros (Scripps Clinic, La Jolla, CA) showed that patients with HCV genotype 1 infection and stage 4 or 5 chronic kidney disease appeared to benefit from a combination of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak), with ribavirin (for HCV genotype 1a infection) or without ribavirin (for genotype 1b infection). Preliminary results from this 12-week regimen showed elimination of the virus without worsening renal function, reported in the late-breaking abstract session on April 25.
According to Medpage Today, viral loads in all patients rapidly reduced with treatment. All patients who reached post-treatment week 4 achieved a sustained virologic response (SVR) at that time point, Pockros et al reported. No virologic failures, premature discontinuations, or treatment-emergent adverse events had been observed.
At the time of Pockros’s presentation, 20 patients (mean age 60 y, 17 men) had been enrolled in the phase 3b study; 14 had finished the regimen and 6 were still being treated. The study included treatment-naïve patients with rates of glomerular filtration less than 30 cc/minute; 13 patients were on dialysis.
HCV infection is common among patients with end-stage renal disease, but none of the all-oral treatment regimens have been approved by the US Food and Drug Administration for this population. Although the study did not include patients with cirrhosis, a future study will include patients with cirrhosis and eliminate ribavirin, which did not seem to provide much benefit to this population.
Kenar Jhaveri (Hofstra North Shore-Long Island Jewish School of Medicine, NY) told MedPage Today that treating HCV in patients with severe kidney disease has the potential to improve kidney outcomes. He said that in patients with HIV infection and kidney disease, kidney health improves with HIV suppression—the same might occur in patients with HCV and renal disease.
In the same session, Fred Poordad (University of Texas Health Science Center at San Antonio) reported that a 12-week combination of daclatasvir and sofosbuvir was highly effective in 60 patients with advanced cirrhosis and 53 with HCV infection following liver transplantation.
MedPage Today explained that the advantage of pairing daclatasvir with sofosbuvir, as opposed to a fixed-dose single pill combination, is that the drugs are not co-formulated, so clinicians can modulate dosing to work around drug interactions.
Poordad reported that overall, 83% of patients with cirrhosis and 94% of patients with disease recurrence after liver transplantation achieved SVR12. In patients with HCV genotype 1 infection, these rates were 82% and 95%, respectively.
Rates of SVR12 among patients with Child-Pugh class A or B cirrhosis were 92% and 94% respectively, but only 56% among patients with Child C class cirrhosis, Poordad reported. However, in most of these patients, model for end-stage liver disease (MELD) scores improved.
The anti-HCV drugs did not appear to interact with immunosuppressants and there was no need to adjust dosing to compensate for other drugs either before or after transplantation.
Patients were allowed to continue in the study if they went on to receive liver transplants. Four did so (including 1 patient who received a liver from a genotype 1-infected donor) and all reached an SVR12 after 12 weeks of post-transplant treatment. Because MELD scores are used to determine transplant eligibility, one of the co-moderators questioned whether we were doing patients a favor by improving their MELD scores, and thereby reducing their ability to get a new liver.