1(OH) Vitamin D3 Supplementation Improves the Sensitivity of the Immune-Response during Peg-IFN/RBV Therapy in Chronic Hepatitis C Patients-Case Controlled Trial

Kondo, Yasuteru; Kato, Takanobu; Kimura, Osamu; Iwata, Takashi; Ninomiya, Masashi; Kakazu, Eiji; Miura, Masahito; Akahane, Takehiro; Miyazaki, Yutaka; Kobayashi, Tatsuya; Ishii, Motoyasu; Kisara, Norihiro; Sasaki, Kumiko; Nakayama, Haruo; Igarashi, Toshihiro; Obara, Noriyuki; Ueno, Yoshiyuki; Morosawa, Tatsuki; Shimosegawa, Tooru

doi:10.1371/journal.pone.0063672

Cited by 26 publications

(27 citation statements)

References 41 publications

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“…In addition, increase in ISG expression in CHC patients predicted poorer responses to the treatment [30, 31]. The finding of reduction of ISG expressions in the liver and serum IP-10 levels, however, were criticized as an adaptive immune stabilizing effect of vitamin D on the out of control immune responses in CHC patients [29]. Our data showed the same evidence of IP-10 reduction within 6 weeks, however, without influences of interferon.…”

Section: Discussionsupporting

confidence: 71%

“…The link between vitamin D and IP-10 was demonstrated, in vitro , in LPS-stimulated primary human monocytes, which the expression of IP-10 was suppressed by vitamin D [13]. In CHC patients treated with vitamin D/pegylated interferon/ribavirin showed significant reduction of serum IP-10 within 4 weeks of treatment and lower interferon stimulating gene (ISG) mRNA expression in hepatocytes as compare to the control arm without vitamin D [29]. The reduction of inflammatory responses, however, seemed paradox to explain the benefit on viral eradication.…”

Section: Discussionmentioning

confidence: 99%

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Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial

et al. 2017

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Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC.Trial registration: Thai Clinical Trials Registry TCTR20160429001

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial

et al. 2017

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“…In addition to serum cytokines, the frequency of specific immune subsets including myeloid-derived suppressor cells (MDSCs) and regulatory T cells could be a useful biomarker for managing HCC [56,57]. In addition to HCC patients, chronic hepatitis B, chronic hepatitis C and NASH patients have distinct immune cell profiles [58][59][60][61][62][63]. Therefore, for HCC, we should also consider background liver diseases.…”

Section: Novel Cytokine and Protein Biomarkersmentioning

confidence: 99%

Significant biomarkers for the management of hepatocellular carcinoma

Kondo

Kimura

Shimosegawa

2015

Clin J Gastroenterol

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Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC.

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“…[118][119][120] The exact mechanism of its antiviral effect is unknown, although it was recently shown to amplify the innate antiviral immune response by upregulating the expression of interferon-b and the MxA gene and dampening IP-10 expression. 115,121 Furthermore, vitamin D has been shown to directly inhibit the proliferation and the profibrotic effect of hepatic stellate cells. 122 Studies conducted among HIV-HCV coinfected persons also show association between vitamin D and liver fibrosis.…”

Section: Hepatitis Cmentioning

confidence: 99%