We read with great interest the article by Petta et al.1 regarding the association of 25-OH vitamin D (25[OH]D) levels with the response to interferon-based therapy in genotype 1 (G1) chronic hepatitis C (CHC). They found that low 25[OH]D levels were associated with severe fibrosis and low responsiveness to interferon-based therapy in this patient group. Although the authors discussed their findings comprehensively, we think that there are two additional issues that need to be clarified.
First, a great number of studies have indicated that low serum 25[OH]D levels are associated with metabolic syndrome and obesity.2 Ford et al.3 showed that low serum 25[OH]D levels are associated with metabolic syndrome in US adults. Additionally, insulin resistance and CHC infection are clearly linked. Moreover, insulin resistance is a parameter for the response of therapy in G1 CHC.4 However, the authors apparently did not find a similar correlation in their patient group. For that reason, we think that it would have been noteworthy if the authors had taken into consideration the potential effects of metabolic syndrome and particularly insulin resistance on their results.
Second, chronic renal failure, thyroid metabolism disorder, and longstanding immobilization might negatively effect the bone metabolism and change the 25[OH]D levels. Moreover, statin use may potentiate the interferon response in CHC.5 Also, statin therapy may alter 25[OH]D levels in favor of elevation. The inhibition of cholesterol synthesis with statin use causes an excess of 7-dehydrocholesterol, which is the precursor for vitamin D synthesis.6 From this point of view, it is obvious that the authors did not offer any exclusion criteria regarding the aforementioned parameters.
In conclusion, the study reported by Petta et al.1 undoubtedly provides valuable insight into the pathophysiological basis of the low responsiveness to interferon-based therapy in G1 CHC. However, vitamin D metabolism and metabolic syndrome are substantial confounders that make a clear-cut judgment difficult.