Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
CLINICAL MARKERS OF THE METABOLIC SYNDROME ARE ASSOCIATED WITH HCV GENOTYPE 1 INFECTION AND ARE STRONG NEGATIVE PREDICTORS OF EARLY VIROLOGICAL RESPONSE
E. Jaeckel1*, E. Zehnter2, C. John3, T. Lutz4, W. Schmidt5, R. Link6, P. Geyer7, G. Teuber8, M. Stern9, H.R. Bruch10, K.H. Hey11, R. Heyne12, B. Moeller12, G. Bellmann13, A. Schober14, S. Stoll15, M.P. Manns1
1Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, 2Center of Gastroenterology, Dortmund, 3Center of Gastroenterology, Berlin, 4Infektiologikum, Frankfurt, 5MVZ-Aerzteforum Seestrasse Dres. C. Mayr / PD W. Schmidt, Berlin, 6Clinic for Internal Medicine, St. Josefs Hospital, Offenburg, 7Center of Gastroenterology, Huenfeld, 8IFS, Stresemannallee 3, Frankfurt/M, 9Center of Internal Medicine, Frankfurt, 10Center of Gastroenterology, Bonn, 11Center of Gastroenterology, Paderborn, 12Center of Gastroenterology and Livercenter, 13General Practice, Berlin, 14Center of Gastroenterology, Goettingen, 15Roche Pharma AG, Grenzach-Wyhlen, Germany. *firstname.lastname@example.org
Background: Insulin resistance (IR) has been documented in patients chronically infected with hepatitis C virus (HCV), but the association with specific genotypes is still controversial. Yet it has been observed that IR or presence of the metabolic syndrome might have a negative influence on antiviral treatment responses.
Methods: The German gastroenterologists in private practice are conducting a Germany-wide, non-interventional study in cooperation with Roche. Within this observational study markers of insulin resistance and cardiovascular risk parameters are investigated.
Results: In this Interim-analysis of 2501 patients receiving therapy with PEG-interferon alfa-2a 180 µg and ribavirin were evaluated for cardiovascular and metabolic risk markers and prospectively followed. 62.9% of patients were male. 61.8% were infected with GT1, 6.2% with GT2, 28.1% with GT3, 3.6% with GT4 and 0.2% with GT5/6. Patients infected with GT1,4,5 more often had high viral load (> 400.000 IU/ml) and longer duration of infection (12.8 vs. 10.8 years) compared with GT2,3 infected patients. At baseline GT1,4,5 patients more often presented signs of metabolic syndrome: BMI>27 kg/m2 (31% vs. 24) and elevated triglyceride levels (30% vs. 23%). Early virological response at week 12 (>2 log decline of viral load or HCV-RNA undetectable) (EVR) was observed in 89.8%. Markers of metabolic syndrome (obesity, hypertension, elevated triglycerides and blood sugar) and diabetes were predictive of initial non-response (NR). Multivariate regression analysis identified GT1,4,5 (OR 7.98), BMI>27 (OR 2.70), triglycerides>150mg/dl (OR1.82) and fasting glucose>110mg/dl (OR1.82) as independent parameters for NR, while surprisingly a total cholesterol>190mg/dl was associated with improved EVR (OR0.45). 1811 patients completed week 24 with a virological response of 80.3%. Although parameters of metabolic syndrome were negative predictive parameters for a virological response at week 24, multivariate analysis just revealed GT1,4,5 to be predictive of virological response at week 24 once EVR had been achieved.
Conclusions: Patients infected with GT1,4,5 have more often signs of metabolic syndrome. More importantly elevated BMI, triglycerides and glucose were negative, independent prognostic parameters for EVR besides viral genotype, while elevated cholesterol levels predicted a better response at week 12. IR therefore identifies difficult to treat patients who might warrant further treatment options.