Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
METABOLIC SYNDROME (MS) IS A NEGATIVE PREDICTOR OF TREATMENT OUTCOME IN PATIENTS WITH CHRONIC HEPATITIS C: RESULTS FROM THE IDEAL STUDY
M.S. Sulkowski1*, J.W. King2, S.A. Harrison3, L. Rossaro4, K.-Q. Hu5, E.J. Lawitz6, M.L. Schiffman7, A.J. Muir8, G.W. Galler9, J. McCone10, L.M. Nyberg10, W.M. Lee11, R. Ghalib12, J.G. McHutchison8, S. Noviello13, V.S. Goteti13, J.K. Albrecht13, C.A. Brass13
1Viral Hepatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, 2Louisiana State University Health Sciences Center, Shreveport, LA, 3Brooke Army Medical Center, Fort Sam Houston, TX, 4University of California Davis Medical Center, Sacramento, 5University of California-Irvine Medical Center, Irvine, CA, 6Alamo Medical Research, San Antonio, TX, 7Bon Secours Health System, Liver Institute of Virginia, Newport News, VA, 8Duke Clinical Research Institute, Durham, NC, 9Kelsey-Seybold Research Foundation, Houston, TX, 10Southern California Permanente Medical Group, San Diego, CA, 11University of Texas Southwestern Medical Center at Dallas, 12The Liver Institute at Methodist Dallas, Dallas, TX, 13Schering Corp., a Division of Merck & Co., Kenilworth, NJ, USA. *email@example.com
Background/aims: Small studies have suggested that metabolic syndrome and its various components are associated 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-naïve, HCV genotype-1 infected adults received peginterferon (PEG) alfa-2b 1.5 or 1 µg/kg/wk plus ribavirin (RBV) 800-1400 mg/d or PEG alfa-2a 180 µg/wk plus RBV 1000-1200 mg/d. Metabolic syndrome was defined by the IDF/AHA criteria requiring 3/5 of:
1) fasting glucose≥5.6 mmol/L or use of diabetes medications,
2) elevated blood pressure (≥130/85) or use of anti-hypertensivemedications,
3) triglycerides>150 mg/dL,
4) HDL-C< 40 mg/dL (males) or < 50 mg/dL (females),
5) central obesity with waist circumference>102cm (males) or 88cm (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.