More recently, serum vitamin D levels emerged as a new modifiable predictor of SVR.6 Vitamin D deficiency was associated with lower SVR rates in HCV-positive patients treated with IFN plus ribavirin in comparison to patients with normal serum vitamin D levels; this suggests that vitamin D supplementation could be helpful in enhancing the responsiveness to antiviral therapy. Vitamin A deficiency has been found to be an important factor in conditioning a more severe course

of viral infections such as measles.7 Vitamin A can up-regulate the expression of type I IFN receptor, enhancing the anti-HCV replication effect of IFN-α.8 In a cohort of previous nonresponder patients with HCV chronic infection,9 all-transretinoic-acid (ATRA) demonstrated a direct antiviral and a strong additive or synergistic effect with 3-MA molecular weight pegylated IFN. Nevertheless, only few studies are available regarding the prevalence of vitamin A deficiency in HCV chronically

infected patients10, 11; furthermore, the potential effect of vitamin A in modifying the antiviral action of IFN and ribavirin has never been studied. The aims of the present study were: (1) to investigate the prevalence of vitamin A deficiency among patients with chronic HCV infection; (2) to assess whether vitamin A deficiency could be associated with the absence of responsiveness to IFN plus ribavirin-based antiviral therapy; and (3) to evaluate the possible additive effect of vitamin A and vitamin D deficiency in influencing nonresponse. ATRA, all-transretinoic-acid; cEVR, complete early viral response; DAA, direct

antiviral agent; EOT, end of treatment viral response; Ponatinib HCV, hepatitis selleckchem C virus; HOMA, homeostasis model assessment; IFN, interferon; IL-28B, interleukin 28B; RVR, rapid viral response; SVR, sustained viral response. The study population included a total of 199 consecutive, HCV-positive treatment-naïve patients of Caucasian ethnicity who received antiviral therapy at one of three academic centers in northern Italy (Medical Liver Transplantation Unit, University of Udine [N = 67; 33.7%], Department of Gastroenterology, University of Verona [N = 85; 42.7%], Department of Clinical and Experimental Medicine, University of Novara [N = 47; 23.6%]) from September 2005 to October 2009. Chronic HCV hepatitis was defined by the presence of anti-HCV antibodies, serum HCV RNA positivity, and the persistent elevation of alanine aminotransferase (ALT) for at least 6 months. In addition, 131 patients had a liver biopsy performed within the 6 months preceding the start of antiviral therapy. Exclusion criteria were: (i) decompensated liver cirrhosis (Child-Pugh score >6); (ii) the presence of hepatocellular carcinoma (HCC); (iii) HIV coinfection; (iv) HBV coinfection; (v) autoimmune liver disease, defined according to validated diagnostic criteria12; (vi) genetic liver disease (e.g.