Many patients develop recurrent hepatitis C virus (HCV), following liver transplantation (LTx).
Although there is no completely satisfactory treatment for recurrent HCV, a combination of interferon-alpha (INF) and ribavirin remains the most widely used.
Ribavirin is eliminated through the kidneys, therefore tends to accumulate in the presence of renal dysfunction.
|Hemolysis significantly associated with high serum creatinine and decreased creatinine clearance.|
The primary side effect of ribavirin is hemolysis.
In this study, published in the November issue of Liver Transplantation, the research team compared the incidence of hemolysis with renal function in LTx patients with recurrent HCV, who were being treated with ribavirin.
The team examined the incidence of hemolysis and the renal function in 72 patients (58 male, 14 female).
All patients had recurrent HCV, and were receiving INF and ribavirin.
The team grouped the patients according to the percentage decrease of hematocrit, after the introduction of ribavirin.
The patient's baseline serum creatinine and creatinine clearance calculated using the Cockcroft-Gault formula.
Percentage decrease of hematocrit after ribavirin treatment was also compared with creatinine clearance as a continuous variable.
In addition, patients were analyzed in three groups: creatinine clearance of ≥70 ml per min (group A), creatinine clearance <70 ml per min and ≥40 ml per min (group B), and creatinine clearance <40 ml per min (group C).
The research team found that 63% of patients experienced a significant decrease (≥15%) in hematocrit after starting INF and ribavirin.
The mean serum creatinine was 1 mg/dl in this group, and the mean calculated creatinine clearance was 71 ml/min.
However, in the 27 patients, who did not show a significant decrease in hematocrit, the mean serum creatinine was 1 mg/dl, and the mean creatinine clearance was 95 ml/min.
On continuous variable of calculated creatinine clearance, the trend was a decrease in hematocrit following ribavirin treatment, compared with pretreatment.
The team found that the rate of hemolysis was significantly different in group A (54%), group B (71%), and group C (100%).
They found the incidence of hemolysis was significantly associated with higher serum creatinine and decreased creatinine clearance.
Dr Ashok Jain's team concluded, "Because ribavirin is eliminated by the kidneys, this observation points to the need for adjustments in the dose of this agent in LTx patients, who tend to have some degree of renal dysfunction, to reduce the incidence of hemolysis".
"Further pharmacokinetic studies of ribavirin in LTx patients with varying degrees of renal function may allow the development of an algorithm for the safer use of ribavirin in HCV-positive LTx patients".