In a phase 2 clinical trial, the use of simeprevir in combination with daclatasvir and sofosbuvir resulted in sustained virologic response (SVR) 12 weeks after the end of treatment in 100% of patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection and portal hypertension or decompensated liver disease. Results were reported in the Journal of Viral Hepatitis.
The IMPACT study (ClinicalTrials.gov Identifier: NCT02262728) enrolled 19 adults with clinically compensated cirrhosis (Child-Pugh score <7) and documented presence of portal hypertension and 21 patients with decompensated liver disease (Child-Pugh score 7-9). Both treatment-naive and treatment-experienced patients were included. All received a regimen consisting of 3 direct-acting antivirals (DAAs) with distinct mechanisms of action and non–overlapping resistance profiles: simeprevir 150 mg, daclatasvir 60 mg, and sofosbuvir 400 mg once daily for 12 weeks.
In an email interview, lead investigator Eric Lawitz MD, clinical professor of medicine at the Texas Liver Institute, University of Texas Health Science Center in San Antonio, Texas, told Infectious Disease Advisor that the study population included a high representation of certain baseline characteristics that have been associated with lower response to treatment: Hispanic or Latino (58%), with non-CC IL28B genotype (83%), body mass index (>28.5 kg/m2), and HCV genotype 1a infection (65%). Baseline NS3 Q80K, a naturally occurring polymorphism associated with low-level resistance to simeprevir in vitro, was present in 12 of 25 (48%) patients infected with HCV genotype 1a with sequencing data available; 3 patients had baseline daclatasvir resistance-associated variants (RAVs).
Regardless of the presence of the various factors influencing response to treatment, all patients in the study achieved SVR at 12 and 24 weeks. Treatment was generally safe and well tolerated; no deaths or adverse events leading to study discontinuation occurred. Mild or moderate adverse events were reported in 26 of 40 patients (65%). Patients who participated in the study will be followed for a period of 5 years after the end of treatment to fully assess the long-term benefit associated with SVR.
Dr Lawitz told Infectious Disease Advisor that physicians treating patients with HCV-related decompensated liver disease must carefully assess whether the immediate eradication of the HCV infection will be more beneficial than performing a liver transplant first and effectively treating the infection afterward. “It is unclear if eradication of HCV in patients with decompensated liver function is associated with significant improvement of the liver disease, to the point that the patient will not require subsequent liver transplant,” he noted, adding that the point at which a patient will fail to benefit from treatment, regardless of SVR, has yet to be defined and remains controversial. “However, what is very important to mention is that differently from not too many years ago, if a physician considers that eradicating HCV infection in a patient with HCV-related decompensated liver disease is in the best interest of the patient, therapeutic alternatives that are efficient and seemingly well tolerated are available.”
Lawitz E, Poordad F, Gutierrez JA, et al. Simeprevir, daclatasvir and sofosbuvir for hepatitis C virus-infected patients with decompensated liver disease [published online November 29, 2016]. J Viral Hepat. doi:10.1111/jvh.12645