PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of wjgLink to Publisher's site
 
World J Gastroenterol. 2017 February 28; 23(8): 1325–1327.
Published online 2017 February 28. doi:  10.3748/wjg.v23.i8.1325
PMCID: PMC5330816

Hepatitis C infected patients need vitamin D3 supplementation in the era of direct acting antivirals treatment

Abstract

It has been reported that the serum level of vitamin D3 (VitD3) could affect the natural course of chronic hepatitis C (CH-C) and the response to treatment with pegylated interferon (Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of VitD3 supplementation were reported, the total effect of VitD3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)VitD3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals (DAAs) without Peg-IFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of VitD3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding VitD3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD3.

Keywords: Vitamin D, Hepatitis C virus, Direct acting antivirals, Hepatocarcinogenesis, Immune response

Core tip: Although several mechanisms for the favorable effects of vitamin D3 (VitD3) supplementation were reported, the total effect of VitD3 supplementation remains unclear. Recently, the main treatment of chronic hepatitis C should be direct acting antivirals (DAAs) without pegylated interferon (Peg-IFN). Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of VitD3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding VitD3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD3.

INTRODUCTION

It has been reported that the serum level of vitamin D3 (VitD3) could affect the natural course of chronic hepatitis C (CH-C) and the response to treatment with pegylated interferon (Peg-IFN) and ribavirin (RBV)[1,2]. Although several mechanisms for the favorable effects of VitD3 supplementation were reported, the total effect of VitD3 supplementation remains unclear. It has been reported that VitD3, as synthesized in the skin by photolysis from 7-dehydrocholesterol, is transported in the blood to the liver where it is hydroxylated at the C-25-position. Then, it is hydroxylated at the C-1α-position to form the active metabolite 1,25(OH)2VitD3 in the kidney. 1,25(OH)2VitD3 is known to regulate calcium and phosphorus metabolism in skeletal homeostasis. Moreover, 1,25(OH)2VitD3 could affect various kinds of immune cells via vitamin D receptor[3,4]. Several groups reported that the amount of 25(OH)VitD3 affects the progression of CH-C and response to Peg-IFN/RBV treatment. Moreover several mechanisms for the favorable effects of VitD3 supplementation in CH-C patients have been reported[5]. Dr. Azza reported that the serum level of 25(OH)VitD3 in CH-C children was significantly lower than that in healthy children. In addition to the treatment response, the deficiency of VitD3 could affect bone density. Therefore, we should consider supplementation with VitD3 for CH-C patients even in the era of direct acting antivirals (DAAs).

DISCUSSION

After a sustained virological response, the risk of hepatocarcinogenesis remains. Previously, we reported that supplementation with 1(OH)VitD3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control[5]. The induction of a favorable immune response by adding VitD3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients lacking sufficient amounts of VitD3. Another group reported that 1,25(OH)2VitD3 could inhibit HCC development through reducing secretion of inflammatory cytokines from immune-related cells[6]. Moreover, it has been reported that reduced 25(OH)VitD3 serum levels were found to be associated with HCV-related HCC[7]. In addition to the risk of HCC development, 25(OH)VitD3 deficiency could be associated with advanced stages of HCC and it could be a prognostic indicator for a poor outcome[8]. In Japan, hepatocarcinogenesis after achieving SVR is an important issue since many CH-C patients are old and have severe fibrosis. Especially, CH-C patients with severe fibrosis might not have sufficient VitD3 since hepatocytes are necessary to metabolize VitD3. Moreover, it has been reported that there might be a relationship between carcinogenesis and insufficient VitD3[6,9]. Therefore, we should analyze the effect of VitD3 supplementation on hepatocarcinogenesis after achieving SVR[7]. Additionally, the immunological effect of VitD3 might differ between DAAs with and without Peg-IFN.

CONCLUSION

Recently, the main treatment of CH-C should be DAAs without Peg-IFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of VitD3 after treatment of DAAs without Peg-IFN.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: Japan

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

Conflict-of-interest statement: None declared.

Peer-review started: October 25, 2016

First decision: December 2, 2016

Article in press: December 21, 2016

P- Reviewer: Skaaby T, Stokes CS S- Editor: Yu J L- Editor: A E- Editor: Zhang FF

References

1. Petta S, Cammà C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, Licata G, Porcasi R, Marchesini G, et al. Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology. 2010;51:1158–1167. [PubMed]
2. Abu-Mouch S, Fireman Z, Jarchovsky J, Zeina AR, Assy N. Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naïve patients. World J Gastroenterol. 2011;17:5184–5190. [PMC free article] [PubMed]
3. Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M. Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol. 2014;5:151. [PMC free article] [PubMed]
4. Ryynänen J, Carlberg C. Primary 1,25-dihydroxyvitamin D3 response of the interleukin 8 gene cluster in human monocyte- and macrophage-like cells. PLoS One. 2013;8:e78170. [PMC free article] [PubMed]
5. Kondo Y, Kato T, Kimura O, Iwata T, Ninomiya M, Kakazu E, Miura M, Akahane T, Miyazaki Y, Kobayashi T, et al. 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. PLoS One. 2013;8:e63672. [PMC free article] [PubMed]
6. Guo J, Ma Z, Ma Q, Wu Z, Fan P, Zhou X, Chen L, Zhou S, Goltzman D, Miao D, et al. 1, 25(OH)2D3 inhibits hepatocellular carcinoma development through reducing secretion of inflammatory cytokines from immunocytes. Curr Med Chem. 2013;20:4131–4141. [PMC free article] [PubMed]
7. Lange CM, Miki D, Ochi H, Nischalke HD, Bojunga J, Bibert S, Morikawa K, Gouttenoire J, Cerny A, Dufour JF, et al. Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development. PLoS One. 2013;8:e64053. [PMC free article] [PubMed]
8. Finkelmeier F, Kronenberger B, Köberle V, Bojunga J, Zeuzem S, Trojan J, Piiper A, Waidmann O. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma - a prospective cohort study. Aliment Pharmacol Ther. 2014;39:1204–1212. [PubMed]
9. Fedirko V, Duarte-Salles T, Bamia C, Trichopoulou A, Aleksandrova K, Trichopoulos D, Trepo E, Tjønneland A, Olsen A, Overvad K, et al. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study. Hepatology. 2014;60:1222–1230. [PubMed]

Articles from World Journal of Gastroenterology are provided here courtesy of Baishideng Publishing Group Inc