 |
|
|
| |
| |
EFFICACY AND TOLERABILITY OF PREEMPTIVE INTERFERON (IFN) VERSUS IFN PLUS RIBAVIRIN (RBV) TREATMENT IN HEPATITIS C VIRUS (HCV) INFECTED LIVER TRANSPLANT RECIPIENTS
|
|
| |
| |
Reported by Jules Levin
Norah A Terrault and colleagues reported study results in an important oral session (University of California San Francisco, San Francisco, CA) on when to treat HCV after recurrence following liver transplantation.
Recurrent and progressive HCV disease is the most common cause of graft loss in HCV-infected liver transplant (LT) recipients. Strategies to prevent or ameliorate recurrent disease are needed. Initiation of antiviral therapy in the early post-transplant period, prior to overt evidence of HCV recurrence (i.e. preemptive therapy) may enhance rates of HCV eradication.
The aim of this study was to determine the efficacy and tolerability of preemptive IFN versus IFN/RBV in anti-HCV positive LT patients. Consecutive and eligible LT recipients from a single center were enrolled. The goal was to initiate treatment within 6 wks of LT.
Patients were randomized to IFN or IFN plus RBV (400mg daily X 2wks, then 800mg daily X 2 wks, then 1.0-1.2g daily based upon body weight 75 kg). Induction therapy with daily IFN was used for the first 8 wks (1.5MU daily X 2wks, then 3MU daily X 6 wks) followed by 3 MU TIW (N=39) or peg-IFN 1.5 ug/kg/wk (N=10) for 40 wks.
Key inclusion criteria were stable clinical status, Cr45,000 and WBC>3.0. Dose reductions for side effects, especially cytopenias were standardized. Growth factors were given for neutropenia (ANC<1000) and anemia (Hgb<9.0g/dL) beginning 7/2001.
Virological (VR) and biochemical responses (BR) were evaluated at end-of-treatment (ET) and 6 months post-treatment (sustained virological (SVR) and biochemical (SBR) responses).
Between 12/99 and 6/02, 107 LT for HCV were performed; 63 (59%) patients met eligibility criteria and 49 were enrolled (80% males, median age 50 yrs).
Treatment was initiated 5.1 weeks (median, range 1.7-9.3) post-LT. A total of 24 LT patients were randomized to treatment with IFN (71% genotype 1, 48% high viral load, VL) and 25 to IFN plus RBV (68% genotype 1, 46% high VL).
Five patients dropped out after randomization but prior to treatment, 19 discontinued treatment due to adverse events, and 25 patients completed 48 wks treatment. Five patients died during the treatment period of non-treatment related causes. Full doses of IFN and RBV were obtained in 84% and 23% respectively; the median dose of RBV was 360 mg/day.
End of treatment biochemical response (ET-BR) and sustained biochemical response (SBR) were obtained in 64% and 53% of treated patients, with higher rates of ET-BR in patients completing 48 weeks treatment (74% vs. 38%, p=0.02).
End of treatment virologic response (ET-VR) and sustained viral response (SVR) were obtained in 12% and 11% (2 ET-VRs still in follow-up). SVR was more frequent in patients with undetectable HCV RNA by quantitative assay (qHCVRNA) pre-treatment (67% vs 4% with measurable qHCVRNA, p=0. 0009).
Neither time from LT to treatment, age, receipt of full-dose IFN or RBV, genotype, nor treatment group (table below) were associated with response.
Histological disease was mild in the majority of patients at treatment end (78% stage 0 fibrosis and 72% grade 1 or less necroinflammatory activity).
The authors concluded that preemptive antiviral therapy was applicable to ~60% of transplanted patients. Biochemical responses were frequent but SVRs uncommon. Treatment discontinuation and lowering of RBV doses due to side effects likely reduced SVRs and may have limited our ability to detect differences between treatment groups.
The only predictor of SVR was a negative qHCVRNA pre-treatment, which implies that patients with low VL early post-LT may be the best candidates for preemptive therapy. Compared to historical reports, the severity of histological disease was very mild at 1-year post-LT in the majority of treated patients, suggesting preemptive antiviral therapy may provide important histological benefits.
Response By Treatment Group
|
|
| |
| |
| |
IFN |
IFN+RBV |
Pvalue |
| ET BR |
12/22 (55%) |
16/22 (73%) |
0.21 |
| ET VR |
1/21 (5%) |
4/22 (18%) |
0.17 |
| SBR |
10/17 (63%) |
7/15 (47%) |
0.38 |
| SVR |
1/15 (7%) |
2/13 (15%) |
0.46 |
| Stage=0,12 mos |
15/17 (88%) |
10/15 (67%) |
0.47 |
| Grade< or=1,12 mos |
13/17 (76%) |
10/15 (67%) |
0.52 |
|
|
| |
|
|
|
|
|
