Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1–infected patients

Abstract

Hepatitis C virus (HCV) modulates intrahepatic cholesterol biosynthetic pathways to promote viral replication. Chronic HCV infection is associated with altered metabolism, including dyslipidemia and insulin resistance, which contributes to disease progression and influences response to therapy. To further understand the impact of HCV infection on host metabolism, we examined changes in serum lipid profiles and intrahepatic expression of lipid-related genes during interferon (IFN)-free treatment of chronic HCV, genotype-1 infection with sofosbuvir and ribavirin (RBV), and explored associations with treatment outcome. Serum lipids (total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides) and hemoglobin A1C (HbA1C) were measured during treatment, while gene expression of lipid-related genes was assessed using paired pre- and end of treatment (EOT) liver biopsies from 8 patients (n=7 sustained virologic response (SVR), n=1 relapse) and unpaired EOT liver biopsies from 25 patients (n= 17 SVR, n=8 relapse). Serum LDL concentration and particle size increased early in therapy, while triglyceride concentration and very low density lipoprotein (VLDL) particle size decreased concomitantly, irrespective of treatment outcome. While LDL increased in patients regardless of treatment outcome, average LDL concentration was lower at baseline and post-treatment in patients who relapsed. Analysis of paired liver biopsies revealed altered expression of genes associated with lipid transport, assembly, and signaling. In unpaired EOT liver biopsies, intrahepatic expression of fatty acid metabolism and lipid transport genes was lower in patients who experienced treatment relapse. Conclusion Clearance of HCV using an IFN-free antiviral regimen results in rapid changes in peripheral and intrahepatic metabolic pathways, implicating a direct effect of HCV replication on lipid homeostasis.

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

“…Based on these results, the role of metabolic factors as predictors of the DAAs has decreased or even ameliorated. Also, the changes in lipid profile after therapy represented an interesting finding, as recently reported with the use DAAs [12,16]. We found a significant reduction in serum triglycerides and a significant elevation of serum cholesterol, LDL, HDL, and LDL/HDL ratio at 12 weeks post-treatment.…”

“…The direct link between HCV and host lipoproteins explicates the significant interrelationship between HCV and host lipid metabolism, as proved both in vitro [17] and in clinical studies [12]. Meissner et al [12] reported a concomitant decrease in triglycerides and VLDL particle size and a marked increase in serum LDLc after 24 weeks of treating HCV genotype 1 infected patients with SOF/RBV, irrespective of the treatment outcome [12].…”

“…Meissner et al [12] reported a concomitant decrease in triglycerides and VLDL particle size and a marked increase in serum LDLc after 24 weeks of treating HCV genotype 1 infected patients with SOF/RBV, irrespective of the treatment outcome [12]. This might explain a direct effect of HCV clearance on lipid metabolism.…”

“…The highest prevalence of HCV was reported in Egypt, where genotype 4 is responsible for 91% of infections [10] and DAAs represented the main line of treatment in most centers [11]. Although the changes in lipid metabolism after treatment with DAAs were reported for other genotypes [12–14], it was not studied in genotype 4 infected patients. The aim of this study was to evaluate the outcome of using SIM/SOF in treating genotype 4 infected patients and to study the relationship of these agents with lipid profile and IR.…”

The Effect of Hepatitis C Virus Eradication with New Direct Acting Antivirals on Glucose Homeostasis in Non-Diabetic Egyptian Patients

“…Contrary to their expectation, our work showed a marked increase in IR at EOT ( Table 2). Meissner et al, also reported no improvement of IR after treatment with DAA despite lowering of HbA1c in non-diabetic patients [20].…”