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

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 (HDL), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at five clinical time points and by 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<0.0001), but then decreased to 97.7 mg/dL by post-SVR year 1 (P<0.001 compared to DAA; P=0.0013 compared to 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, while only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status.

CONCLUSION: Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the IFN-λ4 protein in metabolic changes observed in HCV-infected patients.