Effect of Vitamin D on PEG-IFN/Ribavirin Therapy for HCV
Chronic HCV–infected patients tend to have vitamin D deficiency, suggesting that vitamin D supplementation may enhance the efficacy of treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). We therefore assessed the effects of vitamin D supplementation on viral response to PEG-IFN/RBV. Eighty-four patients with HCV genotype 1b were randomized, 42 to oral vitamin D supplementation (1000 IU/day) and 42 to nonsupplementation (control), from week 8 to the end of PEG-IFN/RBV therapy. The primary end point was undetectable HCV RNA at week 24 (viral response [VR]). VR rate at week 24 was significantly higher in the vitamin D than in the control group (78.6% vs 54.8% P = 0.037). Adverse events were similar in both groups. When patients were subdivided by IL28B SNP rs8099917 genotype, those with the TT genotype group showed a significantly higher VR rate at week 24 with than without vitamin D supplementation (86.2% vs 63.3% vs P = 0.044). Although patients with the TG/GG genotype, who were relatively resistant to PEG-IFN treatment, had similar VR rates at week 24 with and without vitamin D supplementation, the decline in viral load from week 8 to week 24 was significantly greater with than without vitamin D supplementation. Multivariate analysis showed that rs8099917 genotype and vitamin D supplementation contributed significantly to VR at week 24. SVR rates were similar in the vitamin D and control groups [64.3% (27/42) vs 50% (21/42), P = 0.19]. Vitamin D supplementation may enhance the effects of PEG-IFN/RBV in HCV genotype 1b–infected patients.
Worldwide, about 170 million people are thought to be hepatitis C virus (HCV) carriers, with about 30% developing serious liver diseases such as decompensated cirrhosis and hepatocellular carcinoma (HCC). Eradication of the virus is necessary to prevent the development of such serious conditions. The recent development of triple combination therapy, consisting of pegylated interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor, telaprevir or boceprevir, has improved the sustained virological response (SVR) rate in patients infected with genotype 1 HCV. However, the side effects of these triple therapy regimens may be too severe for patients with comorbid conditions such as anaemia and depression. Furthermore, many patients develop skin rash and appetite loss, resulting in premature termination of treatment These patients, as well as those infected with genotypes other than genotype 1, are therefore treated with PEG-IFN plus RBV.
Blood concentrations of the vitamin D metabolite 25(OH) vitamin D3 are relatively low in patients with chronic hepatitis, especially in those with advanced fibrosis, and may be related to poor responsiveness to IFN-based therapy. Vitamin D supplementation in HCV genotype 1–infected patients treated with PEG-IFN plus RBV has been reported to enhance SVR rates when compared with PEG-IFN/RBV alone (86% vs 42%). In that study, however, vitamin D supplementation was started at the beginning of PEG-IFN/RBV therapy. Some patients, however, achieve a rapid virological response (RVR), defined as undetectable HCV RNA after 4 weeks of PEG-IFN/RBV treatment, with an 80–100% likelihood of achieving SVR; in contrast, patients who do not achieve an early virological response (EVR), defined as undetectable HCV RNA or ≥2-log decrease from baseline at week 12 of therapy, have only an 8% chance of achieving SVR. Several studies have evaluated the effects of extending therapy in slow responders, with undetectable HCV RNA after 24 weeks suggested as a surrogate for SVR. To rigorously evaluate the antiviral effects of vitamin D supplementation in HCV genotype-1 infected patients being treated with PEG-IFN/RBV, we randomized patients who did not achieve RVR to receive or not receive vitamin D supplementation, beginning 8 weeks after the start of PEG-IFN/RBV, and assessed the proportions of patients with undetectable serum HCV RNA after 24 weeks of treatment.
Abstract and Introduction
Abstract
Chronic HCV–infected patients tend to have vitamin D deficiency, suggesting that vitamin D supplementation may enhance the efficacy of treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). We therefore assessed the effects of vitamin D supplementation on viral response to PEG-IFN/RBV. Eighty-four patients with HCV genotype 1b were randomized, 42 to oral vitamin D supplementation (1000 IU/day) and 42 to nonsupplementation (control), from week 8 to the end of PEG-IFN/RBV therapy. The primary end point was undetectable HCV RNA at week 24 (viral response [VR]). VR rate at week 24 was significantly higher in the vitamin D than in the control group (78.6% vs 54.8% P = 0.037). Adverse events were similar in both groups. When patients were subdivided by IL28B SNP rs8099917 genotype, those with the TT genotype group showed a significantly higher VR rate at week 24 with than without vitamin D supplementation (86.2% vs 63.3% vs P = 0.044). Although patients with the TG/GG genotype, who were relatively resistant to PEG-IFN treatment, had similar VR rates at week 24 with and without vitamin D supplementation, the decline in viral load from week 8 to week 24 was significantly greater with than without vitamin D supplementation. Multivariate analysis showed that rs8099917 genotype and vitamin D supplementation contributed significantly to VR at week 24. SVR rates were similar in the vitamin D and control groups [64.3% (27/42) vs 50% (21/42), P = 0.19]. Vitamin D supplementation may enhance the effects of PEG-IFN/RBV in HCV genotype 1b–infected patients.
Introduction
Worldwide, about 170 million people are thought to be hepatitis C virus (HCV) carriers, with about 30% developing serious liver diseases such as decompensated cirrhosis and hepatocellular carcinoma (HCC). Eradication of the virus is necessary to prevent the development of such serious conditions. The recent development of triple combination therapy, consisting of pegylated interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor, telaprevir or boceprevir, has improved the sustained virological response (SVR) rate in patients infected with genotype 1 HCV. However, the side effects of these triple therapy regimens may be too severe for patients with comorbid conditions such as anaemia and depression. Furthermore, many patients develop skin rash and appetite loss, resulting in premature termination of treatment These patients, as well as those infected with genotypes other than genotype 1, are therefore treated with PEG-IFN plus RBV.
Blood concentrations of the vitamin D metabolite 25(OH) vitamin D3 are relatively low in patients with chronic hepatitis, especially in those with advanced fibrosis, and may be related to poor responsiveness to IFN-based therapy. Vitamin D supplementation in HCV genotype 1–infected patients treated with PEG-IFN plus RBV has been reported to enhance SVR rates when compared with PEG-IFN/RBV alone (86% vs 42%). In that study, however, vitamin D supplementation was started at the beginning of PEG-IFN/RBV therapy. Some patients, however, achieve a rapid virological response (RVR), defined as undetectable HCV RNA after 4 weeks of PEG-IFN/RBV treatment, with an 80–100% likelihood of achieving SVR; in contrast, patients who do not achieve an early virological response (EVR), defined as undetectable HCV RNA or ≥2-log decrease from baseline at week 12 of therapy, have only an 8% chance of achieving SVR. Several studies have evaluated the effects of extending therapy in slow responders, with undetectable HCV RNA after 24 weeks suggested as a surrogate for SVR. To rigorously evaluate the antiviral effects of vitamin D supplementation in HCV genotype-1 infected patients being treated with PEG-IFN/RBV, we randomized patients who did not achieve RVR to receive or not receive vitamin D supplementation, beginning 8 weeks after the start of PEG-IFN/RBV, and assessed the proportions of patients with undetectable serum HCV RNA after 24 weeks of treatment.
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