By Liz Highleyman

Individuals with genotype 2 and 3 hepatitis C virus (HCV) respond better to interferon-based therapy than those with genotype 1, but a significant proportion still do not achieve a cure, or sustained virological response (SVR) 6 months after completion of treatment.

Two studies presented at the recent 43rd annual meeting of the European Association for the Study of the Liver (EASL) last month in Milan ooked at factors that predict sustained response in such patients.

Study 1

In the first study, Italian researchers looked at predictors of relapse after a short duration of treatment with pegylated interferon plus ribavirin among patients who experienced rapid virological response (RVR) at week 4 of therapy, as well as the response rate in relapsers who received a second, longer course of treatment.

The standard course of therapy for genotype 2/3 patients is 24 weeks, but investigators have explored shorter courses in an effort to reduce side effects and cost. The relatively high rate of relapse after a 12-16 week course of treatment is the main concern with regard to shortening treatment duration for this patient population.

The present study included 790 consecutive patients with HCV genotype 2 or 3 who underwent treatment since January 2005 using 1.5 mg/kg/week pegylated interferon alfa-2b (PegIntron) plus 1000-1200 mg/day weight-based ribavirin.

Patients who cleared HCV RNA at the end of 12-16 weeks of treatment but had detectable viral load at the end of the 24-week follow-up period underwent re-treatment with the same doses of pegylated interferon and ribavirin for 24 weeks.

Results

• Of the 790 total treated patients, 496 (63%) had undetectable HCV RNA at treatment week 4 (about 60% men, mean age 51.6 years).

• In this subgroup, the end-of-treatment (EOT) response rate was 96%.

• The SVR rate was 82%.

• Among the patients with EOT response, 14% relapsed after stopping therapy.

• Factors that predicted relapse after completion of treatment were:

• Age > 45 years;
• Body mass index (BMI) > 27 kg/m2;
• Platelet count <140.000 cells/mm3.

• In a logistic regression analysis, only platelet count (OR 2.5; P=0.001) and BMI (OR 1.7; P=0.036) were independently associated with SVR.

• In the subset of patients without these unfavorable predictors, the relapse rate was 7%.

• 43 of 67 relapsers were re-treated for 24 weeks, and 47 (70%) achieved SVR.

Based on these findings, the researchers concluded that, "Almost all genotype 2 and 3 patients who achieve RVR may be cured with only 12 weeks of pegylated interferon alfa 2b and weight based ribavirin."

Gastroenterology IRCCS, San Giovanno Rotondo, Italy; Internal Medicine Hospital Canosa, Canosa, Italy; Internal Medicine Hospital Casarano, Casarano, Italy; Gastroenterology and Infectious Disease Ospedali Riuniti Foggia, Italy; Internal Medicine Hospital Venosa, Italy.

Study 2

In the second study, Scandinavian researchers looked at the effect of ribavirin concentration on SVR rates in individuals with genotype 2/3 hepatitis C.

In the NORDynamic trial, 382 genotype 2/3 patients at 31 centers were randomized to receive 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 800 mg/day fixed-dose ribavirin for either 12 or 24 weeks. Of these patients, 355 had trough plasma concentration of ribavirin measured at day 29.

Results

• The overall SVR rates were 78% in the 24-week arm and 60% in the 12-week arm (P < 0.001).

• The median concentration of ribavirin at week 4 was 1.5 mg/l among patients who achieved SVR and 1.3 mg/l among non-SVR patients (P < 0.001).

• For the 24-week arm, the positive predictive value (PPV) for SVR at 4 weeks was 91% (41/45) for a ribavirin concentration > 2 mg/l (P = 0.02).

• For the 12-week arm, the PPV was 74% (25/34) (P = 0.12).

• In a multivariate analysis, ribavirin concentration at week 4 was an independent predictor of SVR (OR 2.3; P = 0.002).

"Although 12 weeks of treatment was inferior to 24 weeks of treatment, a higher ribavirin concentration was associated with a significantly increased SVR," the investigators concluded.

"This indicates that a treatment regiment with ribavirin dose based on plasma concentration at week 4 could significantly improve treatment outcome," they added. "We propose this to be examined in a prospective randomized trial."

Odense University Hospital, Odense, Denmark; Gothenborg University, Göteborg, Sweden; Aarhus University, Aarhus, Denmark; Helsinki University, Helsinki, Finland; Bergen University, Bergen, Norway; Uppsala University, Uppsala, Sweden

5/06/08

References

A Mangia, N Minerva, D Bacca, and others. Factors Predictive of Relapse in Genotype 2 and 3 Pts Treated for 12 Weeks with PegIFN Alfa 2b and Weight Based Ribavirin Combination. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.

PB Christensen, AA Alsio, MR Buhl, and others. Ribavirin Concentration at Week Four Is an Independent Predictor for Sustained Virological Response after Treatment of Hepatitis C Genotype 2/3 (NORDynamic Trial). EASL 2008.