Review
Copyright ©The Author(s) 2018.
World J Gastroenterol. Jan 28, 2018; 24(4): 445-460
Published online Jan 28, 2018. doi: 10.3748/wjg.v24.i4.445
Table 2 Representative studies regarding vitamin D status in chronic hepatitis C virus patients
Study populationDiagnosisSample size (n)Study objectiveStudy designLength of follow-upVitamin D cutoff (ng/mL)(%)Main resultsRef.
Italy CHC (n = 197) HCV genotype 1 controls (n = 49)Cross-sectionalNA< 30: deficiency ≥ 30: sufficiency73 27Low vitamin D linked to severe fibrosis and low SVR in IFN-based treatmentPetta et al[6], 2010
United States CHC (n = 218) LC (n = 123) Non-LC (n = 95)Prospective12 wk after cessation of antiviral therapy SVR12: defined as a viral load undetectable or below the level of detection at week 12 after cessation of antiviral treatment< 20: deficiency < 30: insufficiency ≥ 30: sufficiency43 33 24Vitamin D deficiency associated with HCV–related LC and with hepatic function No significant association between SVR12 and serum vitamin D levels at baselineBackstedt et al[18], 2017
Switzerland CHC (n = 269) HCV genotypes 1-4Case-controlNA< 30: deficiency ≥ 30: sufficiency74 26No significant association between SVR and serum vitamin D levels irrespective of genotypesLange et al[20], 2012
Spain CHC genotypes 1-4 (n = 182)Cross-sectionalNA< 20: deficiency < 30: insufficiency ≥ 30: sufficiency36 41 23Vitamin D deficiency not related to biochemical and virological variables or to the stage of fibrosis stageLadero et al[157], 2013
Northern Italy CHC ( = 211) HCV genotypes 1-5Prospective24 wk after cessation of antiviral therapy SVR24: defined as a viral load undetectable or below the level of detection at week 24 after cessation of antiviral treatment< 20: deficiency ≥ 20: sufficiency46.4 53.6SVR24 rates to IFNα therapy were 50%, 61%, and 69% in CHC patients with baseline vitamin D levels of ≤ 10 ng/mL, 10-20 ng/mL, and > 20 ng/mL, respectivelyBitetto et al[25], 2011
Multicenter study, United States Cases (histological progression or clinical decompensation; ( = 129), controls (n = 129)Nested case-control studyOver 4 yrAt baseline: cases: 44.8 controls, 44.0Not statedNo difference in vitamin D levels in patients with and without progression of HCV-associated liver diseaseCorey et al[158], 2012
Multicenter study, Japan CHC (n = 247) HCV genotype 1bCase-controlNA< 20: deficiency < 30: insufficiency ≥ 30: sufficiency At baseline: 22(6–64)Not statedNS5A Y93H and L31M resistance-associated variants associated with vitamin D deficiencyOkubo et al[159], 2016
Multicenter study, France HCV-HIV coinfection (n = 189)Cross-sectionalNA< 30: deficiency ≥ 30: sufficiency85 15Low serum vitamin D levels correlated with liver fibrosis as assessed by FibroTest No association between SVR rate to IFN-based therapy and baseline vitamin D levelsTerrier et al[7], 2011
Japan CHC (n = 619)Cross-sectionalNA< 20: deficiency < 30: insufficiency ≥ 30: sufficiency47 36.7 16.3Vitamin D levels influenced by gender, age, hemoglobin level, albumin and seasonalityAtsukawa et al[160], 2015
Egypt CHC (n = 70) controls (n = 50)Cross-sectionalNAAt baseline Cases: 18.6 Control: 56NAVitamin D decreased in HCV patientsReda et al.[161], 2015
Australia CHC (n = 274) HCV genotype 1Case-controlNA< 20: deficiency < 30: insufficiency ≥ 30: sufficiency16 48 36Baseline vitamin D levels not associated with SVR or fibrosis stage in HCV genotype 1 but deficiency associated with high activityKitson et al[16], 2013
Japan CHC (n = 177)Prospective24 wk after cessation of antiviral therapyNot statedNASVR24 rates: 65% in patients with vitamin D levels > 18 ng/mL vs 38.5% in patients with vitamin D levels of < 18 ng/mLAtsukawa et al[162], 2014
Egypt CHC (n = 101) HCV genotype 4 Vitamin D supplementation group (n = 50), controls (n = 51)Randomized prospectiveUntil 72 wk from start of antiviral therapy SVR was assessed at week 72 from initiation of antiviral treatment< 20: deficiency ≥ 20: insufficiency ≥ 30: sufficiency95 5 0No impact of vitamin D supplementation on SVR in HCV genotype 4 patients No correlation between vitamin D levels and stage of liver fibrosisEsmat et al[15], 2015
Israel CHC (n = 72) HCV genotype 1 Vitamin D supplementation group (n = 36), controls (n = 36)Randomized prospective24 wk after cessation of antiviral treatment< 10: severe deficiency < 20: insufficiency ≥ 20: sufficiency21 59 20Addition of vitamin D to Peg-IFNα/RBV therapy improves SVR24 (86% vs 42%)Abu-Mouch et al[17], 2011
Israel CHC ( = 50) HCV genotype 2 and 3 Vitamin D supplementation group (n = 20), controls (n = 30)Randomized prospective24 wk after cessation of antiviral treatment< 12: deficiency < 32: insufficiency ≥ 32: sufficiency26 54 20Addition of vitamin D to IFNα/RBV therapy improves SVR24 (95% in treated group vs 77% in controls)Nimer et al[21], 2012
France CHC (n = 516) HCV genotype 1Randomized controlledUntil 72 wk from initiation of antiviral therapyNot statedNot statedNo impact of vitamin D levels on efficacy of antiviral therapy in naïve genotype 1 HCV patientsBelle et al[24], 2017
Egypt CHC (n = 66) Vitamin D group (n = 20) controls (n = 30)Randomized prospective24 wk after cessation of antiviral treatment< 12: deficiency < 32: insufficiency ≥ 32: sufficiency33.3 43.3 23.4Addition of vitamin D to conventional Peg-IFNα/RBV therapy improved SVR24Eltayeb et al[26], 2015
Germany CHC (n = 468) HCV genotypes 1-3Retrospective24 wk after cessation of antiviral treatment< 30: deficiency ≥ 30: sufficiency66 34Vitamin D deficiency correlated with SVR in HCV genotype 2 and 3 patients (50% vs 81%: SVR24 for patients with and without severe vitamin D deficiency)Lange et al[80], 2011
Taiwan CHC (n = 132) HCV genotype 1-2RetrospectiveSVR was assessed at week 48 (HCV genotype 1) and at week 24 (HCV genotype 2) from initiation of antiviral treatmentNot statedNot statedVitamin D can suppress HCV replication in hepatic cell lines Vitamin D serum levels associated with both SRV and RVR to Peg-IFNα based therapyJee-Fu et al[13], 2017
Germany CHC (n = 398) HCV genotype 1RetrospectiveSVR was assessed at week 24 from initiation of antiviral treatmentAt baseline 18.7 (3-84.3)Not statedAddition of vitamin D to Peg-IFNα/RBV therapy for treatment-naïve patients with chronic HCV genotype 1: no significant association with SVRGrammatikos et al[94], 2014
Austria HCV-HIV coinfection (n = 65)Retrospective24 wk after cessation of antiviral treatment< 10: deficiency < 30: insufficiency ≥ 30: sufficiency57 23 20Low vitamin D levels may impair virological response to Peg-IFNα/RBV therapy, especially in difficult-to-treat patientsMandorfer et al[163], 2013
Italy CHC (n = 42) Vitamin D supplementation group (n = 15) controls (n = 27)RetrospectiveSVR was assessed at week 48 from initiation of antiviral treatment< 10: severe deficiency < 20: insufficiency ≥ 20: sufficiencyNot statedVitamin D supplementation improves SVR rate following Peg-IFNα/RBV therapy (54% in vitamin D group vs 18.5% in control group)Bitetto et al[98], 2011a
Multicenter study, United States CHC (n = 1292) HCV genotype 1Retrospective24 wk after cessation of antiviral treatment< 12: severe deficiency < 20: insufficiency ≥ 20: sufficiency19 48 33Higher vitamin D levels not associated with SVR in Peg-IFNα/RBV therapyLoftfield et al[27], 2016
Meta-analysis To assess vitamin D levels related to ALF and/or SVR (n = 3755) (11 studies for SVR, 7 studies for ALF)Meta-analysisNA< 10: severe deficiency < 20: deficiency < 30: insufficiency ≥ 30: sufficiencyNot statedLow vitamin D levels related to ALF Low vitamin D levels at baseline in CHC patients were associated with a higher likelihood of having ALF and lower odds of achieving SVRGarcia-Alvarez et al[86], 2014
Meta-analysis To clarify any association between baseline vitamin D levels and SVR (n = 2605) (11 studies)Meta-analysisNANot statedNABaseline vitamin D levels not associated with SVR in Peg-IFNα/RBV therapy, regardless of genotype Effect of vitamin D supplementation on SVR to be determinedKitson et al[95], 2014
Meta-analysis To assess the association of vitamin D levels with the severity of liver fibrosis in CHC (n = 8321) (6 studies)Meta-analysisNANot statedNALower serum vitamin D is a risk factor for severity of liver fibrosis in chronic HCV patients.Luo et al[97], 2014
Meta-analysis To evaluate the association between vitamin D levels and SVR in CHC (n = 1575) (8 observational and 3 interventional studies)Meta-analysisNAAt baseline 17-43 ng/mLNAHigh SVR rates observed in patients with vitamin D levels > 30 ng/mL High SVR rates observed in CHC patients supplemented with vitamin D, regardless of genotypeVillar et al[28], 2013
Meta-analysis To access the association between vitamin D supplementation and SVR rate to PEG-IFN/RBV in CHC (n = 548) (7 studies)Meta-analysisNANANAVitamin D supplementation significantly increased SVR rates to Peg-IFNα/RBV at 24 wkKim et al[96], 2017