Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin.
OBJECTIVE
Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non-TT. Among such treatment-refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non-TT.


METHODS
Patients were randomly assigned to receive simeprevir (100 mg/day) for 12 weeks plus PEG IFN/ribavirin for 24 weeks (control group, n = 58), or vitamin D (2000 IU/day) for 16 weeks including a lead-in phase plus PEG IFN/ribavirin for 24 weeks (vitamin D group, n = 57). The primary end-point was sustainably undetectable viremia 24 weeks after the end of treatment (SVR).


RESULTS
SVR rates were 37.9% in the control group and 70.2% in the vitamin D group. In subgroup analysis, SVR rates of prior null responders were 11.8% and 54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the control group and 66.7% in the vitamin D group. Overall, the SVR rate was significantly higher in patients with high serum 25(OH)D3 levels at the beginning of combination therapy than in those with low serum 25(OH)D3 levels.


CONCLUSIONS
Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory factors.
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai.
Masanori
M
Atsukawa
Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo.
Akihito
A
Tsubota
Chiba Tokushukai Hospital, Funabashi.
Noritomo
N
Shimada
Machida Municipal Hospital, Tokyo.
Kai
K
Yoshizawa
Jikei University School of Medicine Katsushika Medical Center.
Hiroshi
H
Abe
Tokyo Metropolitan Bokutoh Hospital, Tokyo.
Toru
T
Asano
Saiseikai Yokohamashi Tobu Hospital, Yokohama.
Yusuke
Y
Ohkubo
Ibaraki Central Hospital, Ibaraki.
Masahiro
M
Araki
Tokyo Medical University, Ibaraki Medical Center, Ibaraki.
Tadashi
T
Ikegami
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai.
Tomomi
T
Okubo
Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai.
Chisa
C
Kondo
Hakujikai Memorial Hospital, Tokyo.
Yuji
Y
Osada
Nippon Medical School, Tokyo, Japan.
Katsuhisa
K
Nakatsuka
Tokyo Metropolitan Bokutoh Hospital, Tokyo.
Yoshimichi
Y
Chuganji
Tokyo Medical University, Ibaraki Medical Center, Ibaraki.
Yasushi
Y
Matsuzaki
Nippon Medical School, Tokyo, Japan.
Katsuhiko
K
Iwakiri
Jikei University School of Medicine Katsushika Medical Center.
Yoshio
Y
Aizawa
native vitamin D; pegylated interferon; ribavirin; simeprevir; sustained virological response