provides fascinating new data and urges further studies of IL28B genotype and response to PEG-IFN in CHB. However, the association of IL28B genotype distribution with that of HBV genotype may introduce an important pitfall. Therefore, we strongly recommend that future studies of IL28B in

CHB be stratified by, or adjusted for, HBV genotype. Milan J. Sonneveld MSc*, Willem P. Brouwer MD*, Harry L.A. Janssen MD, PhD*, * Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. “
“We read with great interest the article by Romero-Gomez et al.1 They found that treating female patients infected with hepatitis C genotype 1 and who had insulin resistance with metformin on top of standard of care could improve insulin

sensitivity and double the sustained LBH589 virologic response (SVR) rate. In addition, those who reached a homeostasis model assessment of insulin resistance (HOMA-IR) score lower than 2 at week 24 of triple therapy had higher SVR rates. Their results indeed provide important data to improve our understanding about the relationship among metformin, insulin resistance, and SVR; however, several issues deserve further discussion. First, although women with triple therapy of metformin, peginterferon alfa-2a, and ribavirin had twice the SVR rate than those without (58% versus 29%), this doubling effect seemed to be confounded by the very low SVR rate in women without adding metformin. These results should thus

be cautiously interpreted, and the authors may compare the variables between female and male patients who did not receive metformin, Nutlin-3a order in order to understand more about the reasons behind this very low SVR rate. Second, it is generally believed that optimal dose of ribavirin is important to achieve SVR, especially in the early phase of therapy, and weight-based ribavirin is strongly recommended in the clinical practice.2 In this study, the dosage of ribavirin was between 1000 and 1200 mg/day, and the mean body weight was around 80 kg. Therefore, the dosage of ribavirin seemed relatively lower HAS1 in achieving the best SVR rate. In addition, metformin is known to cause more short-term weight loss in women than in men.3 Taken together, whether female patients have an improved SVR rate with metformin due to the drug itself or secondary to weight loss accompanied by higher dose of ribavirin per kilogram body weight awaits further examination. The authors may provide data regarding the change of body weight and ribavirin dose during the course of triple therapy to clarify their impact on SVR rate. Third, patients who reached a HOMA-IR score of less than 2 at week 24 of therapy had a significantly higher SVR rate, suggesting that an increase in insulin sensitivity might exert a positive effect on the SVR rate. Our previous study has shown a positive correlation between serum hepatitis C virus (HCV) RNA level and HOMA-IR.