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Aims: The current treatment of choice is a combination of pegylated interferon-alfa (PegIFN-alfa) plus ribavirin. Prediction of IFN efficacy before treatment has been mainly based on viral characteristics such as viral load and genotype. We therefore analyzed data from a large multicentric German surveillance study in order to identify additional host- related predictors of nonresponse. Methods: Between 9/2003 and 8/2008, 279 active sites treated a total of 4039 patients with weight-based PegIFN-alfa2b and ribavirin. As this is an ongoing surveillance trial, we have performed an interim analysis of formerly untreated noncirrhotic patients with HCV-genotype 1 and nonresponse defined as HCV-RNA-positivity at end of treatment (EOT) as well as at the end of follow-up (EOF) 6 months after end of treatment. Results: 455 treated patients with genotype 1 failed to achieve HCV-RNA-negativity at EOT and EOF, while 614 patients experienced sustained virological response after 6 months of follow-up (SVR). Baseline data and rapid virologic response (RVR) in both groups are shown in the table. Because data were not available in all patients the number of patients fluctuates throughout the subgroups analyzed. No dose reductions of either PegIFN-alfa2b or ribavirin were performed in 437 (71.2%) of patients with SVR and 324 (71.2%) in the nonresponder-group. Reductions of ribavirin have been made in 69 (11.2%) of SVR-patients and 31 (6.8%) of patients with nonresponse, respectively. Only 7/209 (3.3%) nonresponding patients, who were tested for HCV-RNA at week 4, experienced an RVR, while 21.4% of all SVR-patients exhibited an RVR. Conclusions: Regarding baseline predictive values, there is a significant difference in age as well as baseline viral load while other factors such as body weight and BMI seem not to predict nonresponse in noncirrhotic patients. In contrast, RVR may predict low nonresponse rates, as break through after week 4 are rare events. Data were analyzed using standard summary statistics and two-sided 95% confidence intervals.

In the course of HIV infection, the role of interferon-α (IFN-α) seems to be rather paradoxical: “It is possible to view alpha-IFN as either a therapeutical agent or as a major contributor to the pathology associated with AIDS.” (S. Krown, 1992).

with poor response to HCV therapy, or may normalize with HCV eradication. We retrospectively interrogated the IDEAL database to examine the role of MS in HCV therapy. Methods: 3070 treatment-naive, HCV genotype-1 infected adults received peginterferon (PEG) alfa-2b 1.5 or 1mg/kg/wk plus ribavirin (RBV) 800–1400mg/d or PEG alfa-2a 180mg/wk plus RBV 1000– 1200mg/d. Metabolic syndrome was defined by the IDF/AHA criteria requiring 3/5 of: 1. fasting glucose≥5.6mmol/L or use of diabetes medications, 2. elevated blood pressure (≥130/85) or use of antihypertensivemedications, 3. triglycerides >150mg/dL, 4. HDL-C 102 cm (males) or 88 cm (females). Results: 30.3% of patients had MS at baseline, with lower sustained virologic response (SVR) in those with MS (34.9% vs 41.6%, p < 0.001). This difference was greater in women (34.7% vs 43.2%, p = 0.006) than men (35.0% vs 40.5%, p = 0.024). MS was a negative predictor for response (OR=1.3) in nearly all subgroups, with a higher odds ratio in those with advanced fibrosis (OR=1.7). SVR was lower with each additional component of the MS definition present, with the largest decrease from 2 criterion (SVR = 40.0%) to 3 criterion (SVR = 35.5%), which is consistent with the MS definition. Multivariate regression including MS and each of its components shows that elevated glucose has the best negative predictive value (OR=1.72) but ‘high’ HDL is a negative predictor of SVR (OR=1.50); waist circumference and MS are no longer significant predictors of SVR. Patients with both high glucose and HDL (18.1%; 557/3070) had a low probability of SVR (OR=1.97). Removing central obesity from the MS criteria (not measured in FU), 56% of those with baseline MS no longer met diagnostic criteria six months after completion of therapy (48% if SVR, 60% if no SVR) due to normalization of one or more of the other factors. Conclusions: MS is a negative predictor of response to PEG/RBV therapy. Surprisingly, ‘high’ HDL was also a negative predictor of SVR. Independent of SVR, MS normalized in the majority of patients post-therapy.