Ledipasvir–sofosbuvir combination effective, safe in chronic hepatitis C genotype 1 infection
Combination therapy with the NS5A inhibitor ledipasvir and NS5B inhibitor sofosbuvir (LDV/SOF) appears to be highly effective in the management of chronic hepatitis C virus (HCV) genotype 1 (GT1) infection, yielding a sustained virologic response (SVR) of >90 percent without increasing the incidence of serious adverse events, according to data from a real-world Japanese cohort.
Researchers reviewed the medical data of 1,461 GT1-infected patients (mean age, 69 years; cirrhosis, 23.8 percent; history of treatment for hepatocellular carcinoma [HCC], 10.9 percent), treated with LDV/SOF for 12 weeks. Evaluations included the rate of SVR at 12 weeks post-treatment (SVR12), incidence of adverse events and serum markers of HCC.
The overall SVR12 rate was 98.4 percent. Risk factors for treatment failure were cirrhosis (odds ratio, 4.19; p=0.014) and resistance-associated substitutions (RASs) in NS5A at baseline (odds ratio, 7.78; p=0.0004).
The SVR12 rates were 93.0 percent among patients with cirrhosis and NS5A RASs and 100 percent among those without cirrhosis or NS5A RASs.
In the group of patients who achieved SVR, reductions from baseline to end of treatment were observed in the levels of alpha-fetoprotein (AFP; from 13.4 to 6.0 ng/mL; p<0.0001), AFP-L3 (from 2.2 percent to 1.5 percent; p<0.005) and Mac-2 binding protein glycosylation isomer (M2BPGi; from 3.6 to 2.0 cutoff index; p<0.0001).
Adverse events occurred rarely and independent of age. Furthermore, there were no reductions observed in estimated glomerular filtration rate in patients with baseline chronic kidney disease stage 3.
Researchers noted that while the study specifically focused on SVR12 and did not analyse long-term prognosis including HCC occurrence, the finding of reduced M2BPGi in patients who achieved SVR suggests that viral eradication by LDV/ SOF therapy has the potential to reduce HCC risk.