Glecaprevir and Pibrentasvir Improve Extrahepatic Manifestations in Hepatitis C

Treating patients with chronic hepatitis C virus (HCV) with short-term glecaprevir and pibrentasvir improves cardiovascular and metabolic extrahepatic manifestations and results in stable renal function, according to study results published in Infectious Diseases and Therapy.

These results were especially significant in patients with severe extrahepatic manifestations at baseline.

The study included data on all participants without cirrhosis who were treated with glecaprevir and pibrentasvir for 8 weeks in two phase 3 clinical trials (n=505). In addition, a phase 3 trial was carried out to explore the effects of treatment on renal extrahepatic manifestations in participants with advanced renal impairment at baseline. The researchers included all participants with chronic HCV treated with glecaprevir and pibrentasvir for 8 or 12 weeks from five phase 3 trials as a sensitivity analysis. They adjusted for baseline demographics and clinical properties with mixed regression models in order to evaluate changes in extrahepatic manifestations through the end of treatment.

Of 505 participants, 98.4% achieved a sustained virologic response, 14.9% had a body mass index ≥30 kg/m² and 33.5% had a homeostatic model assessment-insulin resistance of ≥2 mU mmol/l².

After 8 weeks of glecaprevir and pibrentasvir treatment, participants had significant declines in triglycerides (−28.6 mg/dl; P <.0001) and glucose (−11.2 mg/dl; P <.0001). Participants did not show significant decline in estimated glomerular filtration rate (mean adjusted change of 2.1 ml/min/m²; P =.34; 95% CI, 2.4 ml/min/m²; 6.9 ml/min/m²).

The researchers found that biomarker improvements were most significant in participants who had elevated triglycerides and/or glucose at baseline.

“This analysis adds to the knowledge of the extrahepatic benefits of HCV treatment with pan-genotypic, short duration, IFN- and sofosbuvir-free [direct-acting antivirals],” the researchers wrote.

Disclosures

The current work was supported by AbbVie Inc. Design and study conduct for the study was approved by AbbVie Inc. AbbVie Inc. participated in the interpretation of data and review and approval of the manuscript. Funding for publication charges was provided by AbbVie Inc. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Reference

Tran TT, Mehta D, Mensa F, et al. Pan-genotypic hepatitis C treatment with glecaprevir and pibrentasvir for 8 weeks resulted in improved cardiovascular and metabolic outcomes and stable renal function: a post-hoc analysis of phase 3 clinical trials [published online October 27, 2018]. Infect Dis Ther. doi:10.1007/s40121-018-0218-x