By Will Boggs, MD
NEW YORK (Reuters Health) Mar 05 - In kidney transplant recipients with chronic hepatitis C, pegylated interferon plus ribavirin does not increase rejection rates and is modestly effective, researchers from Saudi Arabia report.
"Our primary concern in approaching hepatitis C-infected renal transplant patients in our clinical practice was that the evidence citing the poor outcome of interferon-based therapy was, unfortunately, of a poor grade and yet had found its way into guideline recommendations," Dr. Faisal M. Sanai from King Saud University, Riyadh, Saudi Arabia told Reuters Health.
"We believe that in an era of evidence-based practice, clinicians should be willing to challenge established dogmas if the evidence in favor of (or against) a practice is poorly supported by evidence."
Dr. Sanai and colleagues did just that, testing pegylated interferon and ribavirin in a prospective study of 32 kidney recipients with treatment-na�ve chronic HCV. They compared that group with 31 untreated controls who either declined study participation or were considered unsuitable candidates.
Treated patients received pegylated interferon alfa-2a 135-180 mcg/week, plus ribavirin 200-1200 mg/day for 48 weeks. Actual doses were adjusted for glomerular filtration rate.
Twelve patients (37.5%) had a sustained virologic response (SVR) after at least 12 weeks of treatment. Four patients (12.5%) had a rapid virologic response (i.e., within 4 weeks), and 18 (56.3%) had early virologic responses (i.e., within 12 weeks).
Among the 13 patients with end-of-treatment responses, three suffered virologic relapse during follow-up. In addition, two of five patients who stopped treatment due to nonhematological effects also relapsed.
No one developed acute rejection, but four treated patients (12.5%) and eight controls (25.8%) had allograft dysfunction with sustained increases in creatinine at week 96.
The authors say these results compare favorably with those of a recent meta-analysis in which 18% of 102 patients achieved SVR and 30% developed chronic allograft nephropathy.
Two patients had serious nonrenal adverse events, and three patients discontinued treatment - two for grade 3/4 hematological effects and one after withdrawing consent.
All hematological adverse events were transient and returned to baseline levels by week 72, according to the authors' February 19 report online in the Journal of Hepatology.
In binary logistic regression analysis, early virologic response was the only independent predictor of SVR.
"A pegylated peginterferon alpha-2a dose of 135 mcg/week and ribavirin dose of 400 mg/day may be an appropriate dosing strategy in order to improve treatment tolerance without necessarily compromising SVR rates," the researchers conclude. "The results of this study provide an impetus for conducting a larger, randomized controlled trial aiming to define the optimal dosage of peginterferon alpha-2a and ribavirin and identify predictors of graft dysfunction."
"We believe that physicians should be generally heartened to use interferon-based therapy in carefully selected patients with intense monitoring of potential side effects," Dr. Sanai concluded. "Of course, this is true only as long as there is an adequate rationale for the use of this kind of therapy."
He added, "We are now treating qualified HCV patients post renal transplantation under the stringent monitoring criteria we adopted in our study protocol. We will report the post study, real life experience in due course. We would like to see our study as an impetus and encouragement to other groups for conducting larger clinical trials in this area."
J Hepatol 2013.
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