January 8, 2013

Bitetto D. Hepatology. 2012;doi:10.1002/hep.26186.

December 21, 2012

A large number of patients with chronic hepatitis C are vitamin A deficient, and this deficiency is associated with nonresponse to treatment, according to recent results.

In a multicenter study, researchers compared the serum vitamin A and vitamin D levels in 199 treatment-naive patients with chronic hepatitis C, before receiving interferon (IFN)-based antiviral therapy, with those of 119 healthy controls.

Median vitamin A levels were significantly lower among patients with HCV than controls (256 ng/mL compared with 742 ng/mL, P<.0001 for difference). Vitamin A deficiency (200 ng/mL or lower) was observed in 42.2% of patients, compared with none of the controls, with severe deficiency (100 ng/mL or lower) present in 19.6% of cases. Vitamin D deficiency was present in 45.8% of 190 evaluable patients; severe deficiencies in vitamin A and vitamin D (20 ng/mL or lower) existed in 9% of cases.

Patients with severe vitamin A deficiency were more likely to be nonresponsive to treatment (36.1% of cases overall vs. 18.2% of those without severe deficiency, P=.019). HCV genotype 2-3 (P<.001), cirrhosis at baseline (P=.003), IL-28B polymorphism with at least one T allele (P<.001), gGT levels greater than 60 IU/mL (P<.001) and taking 80% or less of the assigned ribavirin dose (P=.002) were predictive of nonresponse.

Among patients with more difficult-to-treat genotypes, multivariate analysis indicated associations between nonresponse to antivirals and HCV RNA levels greater than 600,000 IU/mL (OR=4.39, 1.39-13.8), severe vitamin A deficiency (OR=3.68, 1.03-13.2), IL-28B T/* genotypes (OR=26.3, 4.34-159) and elevated baseline gGT levels (OR=5.24, 1.69-16.2) (95% CI for all).

A second model indicated that patients with low levels of vitamins A and D were at particularly increased risk for nonresponse (OR=12.9, 1.73-96.7). Patients with severe vitamin A deficiency and IL-28BB CT-TT were calculated at the highest risk for nonresponse in a third model evaluating the interaction between IL-28B genotypes and vitamin deficiency(OR=26.5, 2.91-242) (95% CI for all).

“A high percentage of patients with chronic HCV infection presented serum vitamin A deficiency,” the researchers wrote. “This condition is strongly associated [with] nonresponse to antiviral therapy, suggesting that vitamin A serum levels could modulate the responsiveness to IFN-based antiviral therapy. It will be of great importance to verify if vitamin A supplementation could restore the IFN sensitivity in nonresponders, because the success of new [direct antiviral agents] is still conditioned by IFN responsiveness.”

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