Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy

• Published in: The Journal of infectious diseases 2020-01, Vol.221 (1), p.102-109
• Main Authors: Emmanuel, Benjamin, El-Kamary, Samer S, Magder, Laurence S, Stafford, Kristen A, Charurat, Man E, Chairez, Cheryl, McLaughlin, Mary, Hadigan, Colleen, Prokunina-Olsson, Ludmila, O’Brien, Thomas R, Masur, Henry, Kottilil, Shyam
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Alanine Transaminase - blood; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; Aspartate aminotransferase; Aspartate Aminotransferases - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Female; Genotype; Genotype & phenotype; Genotypes; Hepatitis; Hepatitis C; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - metabolism; HIV; Human immunodeficiency virus; Humans; Inflammation; Interferon; Interleukins - genetics; Longitudinal Studies; Low density lipoprotein; Major and Brief Reports; Male; Metabolism; Middle Aged; Patients; Retrospective Studies; Sustained Virologic Response; Triglycerides; Triglycerides - blood
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz435

Abstract Background Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. Methods We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype. Results The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P < .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P < .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. Conclusions Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.