Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin.
Reviewed by: Alan Gaby, MD
Author: Atsukawa M, et al
Reference: Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin. Hepatol Res 2016;46:450-458.
Design: Randomized controlled trial.
Participants: One hundred fifteen patients with chronic hepatitis C genotype 1b and the non-TT variant of the IL28B gene (i.e., the GG or TG variant).
Study Medication and Dosage: All patients received pegylated interferon alpha-2a (PEG IFN), ribavirin, and 100 mg per day of simeprevir for 12 weeks, followed by PEG IFN and ribavirin for 12 weeks. Patients were also randomly assigned to receive vitamin D or no vitamin D (control group). The vitamin D group received 2,000 IU per day of vitamin D for 4 weeks prior to the start of drug therapy; this was continued during the first 12 weeks of drug therapy.
Primary Outcome Measure: Sustained virological response, which was defined as the absence of detectable hepatitis C virus RNA at 24 weeks after the end of treatment.
Key Findings: The sustained virological response rate was significantly higher in the vitamin D group than in the control group (70.2% vs. 37.9%; p < 0.001).
Practice Implications: Protease inhibitors such as simeprevir, when used in combination with PEG IFN and ribavirin, produce a sustained virological response rate of about 90% in patients with chronic hepatitis C genotype 1b who have the rs8099917 genotype TT of the IL28B gene. However, the sustained virological response rate is only about 50% in patients with chronic hepatitis C genotype 1b who have the non-TT genotype of rs8099917. The results of the present study indicate that vitamin D supplementation increased the success rate of conventional drug therapy in the latter subset of patients.
When genetic testing is available, vitamin D should be administered to patients with hepatitis C who fit the appropriate criteria described above. Whether vitamin D should be included as a component of all hepatitis C treatment regimens is less clear. In previous research, vitamin D at a dose of 1,000-2,000 IU per day increased the response rate to PEG IFN and ribavirin in patients with hepatitis C virus genotypes 1, 2, or 3. In contrast, vitamin D tended to interfere with the response to PEG-IFN and RBV in patients with hepatitis C virus genotype 4 (which occurs primarily in the Middle East and Africa).[i] Protease inhibitors, which have recently revolutionized the treatment of hepatitis C, were not administered in those studies.
[i] Gaby AR. Hepatitis. In Gaby AR. Nutritional Medicine, Second Edition. 2017, Concord, NH, doctorgaby.com, chapter 122.