VIENNA — Metabolic syndrome predicts a poor response to treatment for chronic hepatitis C viral infection, according to results from a large trial—but there's a twist.
In the 3,070-patient study, each of the individual components of metabolic syndrome was a negative predictor of sustained virologic response to 48 weeks of antiviral therapy, except one: Surprisingly, a low HDL predicted a favorable response to treatment. And a cardioprotective high HDL level was an independent predictor of treatment failure, Dr. Mark S. Sulkowski reported at the congress.
Another study presented at the congress suggested that intensified doses of the standard antiviral agents—pegylated interferon and ribavirin—could significantly improve treatment success rates in difficult-to-cure hepatitis C genotype 1 patients with metabolic syndrome.
Dr. Sulkowski noted that all of the more than 3,000 participants in the IDEAL study (Individualized Dosing Efficacy versus Flat Dosing to Assess Optimal Pegylated Interferon Therapy) had genotype 1 hepatitis C.
At baseline, 30% met the criteria for metabolic syndrome from the American Heart Association/International Diabetes Federation. Their sustained virologic response (SVR) rate of 35% after 48 weeks of pegylated interferon plus ribavirin was significantly lower than the 42% rate for patients without metabolic syndrome.
The difference was significant in both men and women, although the outcome gap was bigger in women. The SVR in women with metabolic syndrome was 35%, compared with 43% in women without metabolic syndrome. Men with metabolic syndrome had a 35% SVR, compared with 41% in those without the syndrome, reported Dr. Sulkowski, medical director of the viral hepatitis center at Johns Hopkins University, Baltimore.
For each additional component of metabolic syndrome that a patient had, the SVR dropped further. Multivariate regression analysis revealed that an elevated fasting blood glucose was the strongest negative predictor of SVR, with an odds ratio of 1.72 for missing this key end point.
Unexpectedly, a secondary analysis revealed that an HDL of at least 40 mg/dL in men or 50 mg/dL in women was another independent predictor of not attaining an SVR, with an odds ratio of 1.5. The 18% of IDEAL participants with both a high fasting blood glucose and a high HDL at baseline had a twofold increased likelihood of not achieving an SVR after 48 weeks of antiviral therapy.
Six months after completion of therapy, 56% of patients with metabolic syndrome at baseline no longer met criteria for the disorder, Dr. Sulkowski said at the congress, which was sponsored by the European Association for the Study of the Liver.
In an interim analysis of an observational study involving 2,501 German patients being treated for chronic hepatitis C, three factors were found to be independent predictors of failure to achieve an early virologic response at week 12: hypertriglyceridemia, elevated fasting blood glucose, and body mass index of 27 kg/m
The strongest predictor of an early virologic response was hepatitis C genotype 2 or 3. These genotypes were associated with a 7.6-fold greater likelihood of early virologic response compared with genotypes 1, 4, 5, or 6, Dr. Jaeckel said.
Dr. Mitchell L. Shiffman presented a retrospective analysis of 1,135 patients with chronic hepatitis C genotype 1 infection who were treated with pegylated interferon alfa-2a (Pegasys) plus ribavirin in a variety of dosing schedules. Among the 34% of patients classified as having metabolic syndrome, the relapse rate in those randomized to the most intensive treatment regimen was only about half that of patients on standard therapy—24% vs. 47%—reported Dr. Shiffman of Bon Secours Health System, Newport News, Va.
Similarly, the SVR rate at week 72 in patients assigned to the most intensive regimen was 43%, compared with 24% in patients on the standard approved regimen.
The most intensive regimen consisted of pegylated interferon alfa-2a at 360 mcg/week for the first 12 weeks followed by 180 mcg/week out to week 48, accompanied by weight-based dosing of ribavirin at either 1,400 or 1,600 mg daily. The standard regimen was pegylated interferon alfa-2a at 180 mcg/week plus ribavirin at 1,200 mg daily.
This finding, that intensified treatment increases the treatment success rate in difficult-to-cure genotype 1 patients with metabolic syndrome, must be considered hypothesis generating, and requires confirmation in prospective randomized trials, Dr. Shiffman said.
The studies presented by Dr. Shiffman and Dr. Jaeckel were funded by F. Hoffmann-La Roche Ltd.; they serve as consultants to the company. The IDEAL study was supported by Schering-Plough Corp. Dr. Sulkowski disclosed serving as an adviser to Schering-Plough and nine other pharmaceutical companies.
For each additional component of metabolic syndrome, the SVR dropped further.