Interferon-free therapy alters lipid metabolism, glucose homeostasis in chronic HCV patients

October 11, 2013

SAN FRANCISCO – Patients with chronic hepatitis C treated with an interferon-free regimen consisting of sofosbuvir and ribavirin experienced changes in LDL, triglycerides, hemoglobin A1C and metabolic and hepatic lipid gene expression in a study presented at ID Week 2013.

Eric Meissner, MD, PhD, and colleagues administered sofosbuvir with low- or full-dose ribavirin to 60 treatment-naive patients with chronic hepatitis C genotype 1 for 24 weeks, and periodically measured hemoglobin A1C (HbA1c) and serum lipid levels. Paired liver biopsy specimens also were collected from seven patients before and at end of treatment (EOT), and targeted quantitative RT-PCR was performed for genes related to the metabolism of glucose and lipids.

Fifty-five patients completed the study, and 38 maintained a sustained virologic response 24 weeks after EOT (SVR24), with the remainder relapsing after EOT. Investigators observed increases in LDL (91 ± 4 mg/dL to 104 ± 5 mg/dL; P=.0027) and decreases in triglycerides (137 ± 10 mg/dL to 98 ± 8 mg/dL; P<.0001) 4 weeks after treatment initiation, changes that were sustained through EOT.

Patients who relapsed had lower LDL levels than patients who achieved SVR24 at baseline (78 ± 7 mg/dL vs. 97 ± 5 mg/dL; P=.031) and at 48 weeks (82 ± 7 mg/dL vs. 109 ± 6 mg/dL; P=.005), but no difference was observed during treatment or at EOT. Regardless of outcome, glycosylated hemoglobin (HbA1c) was lower 24 weeks after EOT compared with baseline among 39 evaluable patients (P=.0033).

All seven patients who provided biopsy specimens achieved SVR24. Among them, lipid transport genes APOB, APOC3 and APOL3 had significantly up-regulated intrahepatic expression at EOT, while lipid assembly and signaling genes LEPR and MTTP were down-regulated.

“Our data demonstrate changes in lipid metabolism pathways and glucose homeostasis in CHC genotype-1 infection following interferon-free antiviral therapy,” the researchers concluded. “The early changes in LDL and triglycerides associated with treatment implicate a direct effect of viral clearance on lipid homeostasis.”