Table 1.

Current Antiviral HCV Treatment Options for HCV

    IFN-α is a nonglycosylated serum protein produced by immune cells in response to foreign antigen exposure. IFN is filtered by the glomerulus and reabsorbed by the proximal tubular cells, where it undergoes proteolytic degradation. Thus, accumulation of IFN occurs in patients with renal dysfunction. Several forms of IFN are available for therapeutic use, such as α-2a, α-2b, α-n1.
    The main side effects associated with IFN include influenza-like symptoms, hematologic abnormalities, depression, confusion, anorexia, diarrhea, dermatitis, alopecia, increased infection rate, uncontrolled hypertension, heart failure, and pericarditis (60).
Pegylated IFN-α (PEG-IFN)
    A long-acting IFN-α, namely pegylated IFN or peginterferon, produced by the covalent attachment of polyethylene glycol to the IFN molecule, has been developed. Two PEG-IFN formulations are currently approved for treatment of HCV: alfa-2a (PEG-IFN alfa-2a) and alfa-2b (PEG-IFN alfa-2b). Given the increased half-life as compared with conventional IFN, PEG-IFN formulations could be administered weekly. PEG-IFN alfa-2a is metabolized in the liver and kidneys, while PEG-IFN alfa-2b is cleared only by the kidneys. These pharmacokinetic differences account for a slower onset of side effects with PEG-IFN alfa-2a than alfa-2b in the presence of renal dysfunction (128). Adverse events with PEG-IFN therapy are the same as those of IFN.
Ribavirin (RBV)
    RBV is a member of the nucleoside antimetabolite drugs that interfere with duplication of HCV RNA. Bioavailability of oral RBV is increased by 70% in coadministration with a high-fat meal. The principal route of elimination for RBV and its metabolites is the kidney. In patients with GFR less than 30 ml/min the blood area under the curve of RBV is threefold higher than in those with normal renal function. Thus, daily dosage of RBV in patients with chronic kidney disease should be adapted to GFR value and predicted according to specific formulas (129,130). RBV is not removed by hemodialysis (131). The main side effect of RBV is hemolytic anemia related to the high concentration of the drug in red blood cells when the renal clearance is markedly reduced. Indeed, ribavirin is taken up by an active cell surface transporter and phosphorylated to ribavirin triphosphate. Erythrocytes are, however, unable to dephosphorylate or secrete ribavirin triphosphate. As a result, the latter accumulates within the cell and adenosine triphosphate depletion occurs, leading to cell membrane damage. Injured red cells are then removed from the circulation by spleen cells (3). RBV is teratogenic, thus requiring reliable methods of contraception during treatment.