Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients

• Main Authors: Matheus De Lucca Thomaz (Author), Carolina Pinto Vieira (Author), Juciene Aparecida Caris (Author), Maria Paula Marques (Author), Adriana Rocha (Author), Tiago Antunes Paz (Author), Rosamar Eulira Fontes Rezende (Author), Vera Lucia Lanchote (Author)
• Format: Book
• Published: MDPI AG, 2024-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (<i>n</i> = 15, mild to moderate liver fibrosis) or 2 (<i>n</i> = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC_0-24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61-0.93), <i>p</i> < 0.05) but not in Phase 1 (ratio 0.81 (0.66-0.98), <i>p</i> > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97-1.24), <i>p</i> > 0.05) and 2 (ratio 1.03 (0.94-1.12), <i>p</i> > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.

Item Description

10.3390/ph17070865
1424-8247