Researchers say theirs is first national study with a large population to examine possible link.
Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infections does not increase the risk of hepatic decompensation or lead to a decline in renal function, according to a new study.
The incidence of hepatic decompensation in HCV-infected patients treated with Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD) for up to 12 weeks after completion of treatment is comparable to those treated with a sofosbuvir/ledipasvir regimen, and is lower than among those treated with a sofosbuvir/simeprevir regimen, lead author Adeel A. Butt, MD, professor of medicine at Weill Cornell Medical College, told Medical Economics. The risk was predominantly observed in those with pre-treatment cirrhosis, he said.
The researchers published their results in the January 2017 Alimentary Pharmacology & Therapeutics.
In October 2015, the FDA had updated its guidance regarding the safety of the PrOD regimen and ombitasvir, paritaprevir and ritonavir regimen based on 26 worldwide cases of worsening liver injury, hepatic decompensation and liver failure. The guidance was focused on patients with pre-treatment advanced liver disease, specifically those with moderate to severe hepatic impairment (Child-Pugh B and C).
“Those were self-reported cases and no large scale study was available to quantify these risks. Ours is the first national study with a large population to address this question,” said Butt.
Butt and colleagues analyzed all patients treated with these three regimens in the Electronically Retrieved Cohort of HCV Infected Veterans, including 3,728 on PrOD, 1,578 on sofosbuvir/simeprevir, and 10,440 on sofosbuvir/ledipasvir. Incidence rates of hepatic decompensation per 1000 patient-years were 10.6 for PrOD, 32.4 for sofosbuvir/simeprevir and 13 for sofosbuvir/ledipasvir.
Among those with baseline cirrhosis, these rates were 36.9, 61.8 and 41.1, respectively, while among those without cirrhosis at baseline, these rates were 2.7, 7.5 and 2.7. Advanced fibrosis was associated with increased risk of hepatic decompensation in all groups.
“It’s unknown why the incidence and risk of hepatic decompensation is higher among patients treated with sofosbuvir/simeprevir. However, limited pharmacokinetic data combined with higher risk of hepatic decompensation events in our study may suggest a class risk with HCV protease inhibitors,” said Butt.
There are no data from large scale studies about the effect of newer DAAs upon the risk of renal disease. “Patients with HCV infection are at risk for progressive and advanced chronic kidney disease (CKD), which may be due to HCV infection itself or due to the differential prevalence of traditional risk factors in this population. Overall numbers of persons who developed worsening renal function in our study was quite low, and no signal associating it with presence of cirrhosis was detected,” said Butt.
The follow-up time for this outcome was from treatment initiation to the last encounter recorded in the database, which “provides reasonable assurance that progression of CKD is not a major concern with these regimens,” he said.
Butt added: “HCV is now a curable disease in over 90% of those who are treated. The new DAA regimens are much simpler to administer and the adverse effects of treatment are much lower than those encountered in the interferon/ribavirin era. It is imperative to identify patients infected with HCV and refer them for evaluation and treatment.”