Prometheus Index Predicts Hepatitis C Treatment Response

Jim Kling

March 14, 2012

March 14, 2012 (Seattle, Washington) — In patients monoinfected with hepatitis C virus (HCV), a modification of the Prometheus index reliably estimates the probability of achieving a sustained virologic response with pegylated interferon plus ribavirin therapy, according to research presented here at the 19th Conference on Retroviruses and Opportunistic Infections.

This finding, presented at a poster session by José Medrano, MD, a clinical investigator at Hospital Carlos III in Madrid, Spain, could help patients and physicians decide whether to proceed with currently available therapies or to wait for novel therapies that are in development and will likely be available in the near future.

The Prometheus index — which incorporates interleukin (IL)28B variants, HCV RNA level, HCV genotype, and liver fibrosis — has been used to successfully predict sustained virologic response in patients coinfected with HIV and HCV.

To determine the ability of the index to predict response to treatment in HCV-infected patients, Dr. Medrano and colleagues conducted a multicohort study at clinics in France and Spain. The study involved 422 interferon-naïve patients who had undergone elastometry in the previous 12 months to assess liver fibrosis, serum HCV RNA measurement, HCV genotyping, and IL28B testing. The team excluded patients who had discontinued therapy because of adverse effects or who had poor drug compliance.

Of the 422 patients, 245 were coinfected with HIV and HCV and 177 were monoinfected with HCV.

The team found that the Prometheus index was worse at predicting treatment outcome in HCV monoinfected patients (area under the receiver operating characteristic [AUROC], 0.77; 95% confidence interval [CI], 0.70 to 0.84) than in HIV/HCV coinfected patients (AUROC, 0.87; 95% CI 0.83 to 0.92; P = .01).

The team then developed a new index that incorporated HIV status and HCV-1 subtype. They confirmed that a number of variables were independently associated with a failure to achieve sustained virologic response in HCV monoinfected patients: liver stiffness; HCV RNA level; IL28B favorable allelic variants (CT/TT; odds ratio [OR] 5.241; 95% CI, 3.097 to 8.870; P < .01); HCV genotypes 1 to 4 (OR, 9.128; 95% CI, 4.156 to 20.047; P < .01); and HIV-positive status (OR, 1.554; 95% CI, 0.929 to 2.599; P = .09).

The Prometheus index can be used in its current form to predict responses in HCV monoinfected patients, but clinicians "must know that prediction will be less accurate than in HIV/HCV coinfected patients," Dr. Medrano told Medscape Medical News.

The results might find application in settings with limited resources. "You could limit antivirals, which are very expensive, to patients with a lower probability of a virologic response," Dr. Medrano said.

The Prometheus index is available for the iPhone, iPad, and Android phones, but the modified Prometheus index is still being developed and will require further validation, he explained.

The index could help physicians and patients decide whether to pursue antiviral therapy now or to wait for new drugs on the horizon, according to Dawn Fishbein, MD, medical director of SAIC-Frederick's Partnership for HIV/AIDS Progress in Washington, DC, who attended the session.

"The side-effect profile [of currently available drugs] is enormous. It's important when we talk to a patient to say: 'This is the prediction of how you're going to respond now, so perhaps you should wait for newer treatments or you should do treatment now'," Dr. Fishbein told Medscape Medical News.

Dr. Medrano and Dr. Fishbein have disclosed no relevant financial relationships.

19th Conference on Retroviruses and Opportunistic Infections (CROI): Abstract 761. Presented March 7, 2012.

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