Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review

Table 1 Representative studies on vitamin D deficiency in chronic hepatitis B virus patients

Study populationDiagnosisSample size (n)	Study design	Length of follow-up	Vitamin D cutoff (ng/mL)	(%)	Main results	Ref.
China CHB (n = 560)	Multicenter, randomized, controlled	104 wk from initiation of antiviral treatment	< 20: deficiency < 30: insufficiency ≥ 30: sufficiency	21 55 24	Vitamin D insufficiency highly prevalent in treatment-naïve patients with chronic hepatitis B Baseline levels predict virologic response at week 104 after treatment initiation (67% in the insufficiency group vs 82% in the sufficient group)	Yu et al[29], 2017
China CHB (n = 133)	Cross-sectional	NA	< 14: severe deficiency ≥ 14: deficiency < 30 sufficiency	27 66 7	Vitamin D deficiency significantly associated with HBV genotype B	Zhu et al[93], 2016
Vietnam CHB (n = 165) LC (n = 127) HCC (n = 108)	Cross-sectional	NA	< 10: severe deficiency < 20: deficiency < 30: insufficiency ≥ 30: sufficiency	10.4 41.5 32.4 15.7	Vitamin D insufficiency frequent among HBV patients Reduced vitamin D levels significantly associated with clinical progression of LC Vitamin D levels and HBV DNA loads strongly and inversely correlated	Hoan et al[4], 2016
China CHB (n = 115) LC ( = 115) HC ( = 115)	Cross-sectional	NA	< 10: deficiency < 20: insufficiency ≥ 20: sufficiency	83 17 0	Vitamin D levels significantly lower in LC compared to CHB and HC groups (P < 0.001) Child-Pugh score independently associated with vitamin D deficiency (cutoff < 10  ng/mL)	Zhao et al[5], 2016
South Korea CHB (n = 110) Other CLD (n = 97)	Cross-sectional	NA	< 10: deficiency < 20: insufficiency ≥ 20: sufficiency	34.8 45.4 19.8	Vitamin D deficiency independently associated with advanced liver fibrosis	Ko et al[154], 2016
Iran CHB (n = 84)	Cross-sectional	NA	< 10: deficiency < 20: insufficiency ≥ 20: sufficiency	17.9 34.5 47.6	No significant association of vitamin D levels in treated and treatment-naïve patients	Sali et al[155], 2016
Multicenter in Europe, Asia and North America CHB (n = 737)	Randomized, open-label, active-controlled clinical trial	48 wk of TDF + PegIFN 16 wk of TDF + PegIFN followed by 32 wk of TDF 48 wk PegIFN or 120 wk of TDF	< 20: deficiency < 30: insufficiency ≥ 30: sufficiency	58 35 7	Reduced vitamin D levels highly prevalent among untreated CHB patients Low baseline levels of vitamin D associated with high HBV DNA loads, abnormal ALT at week 48 independent of treatment groups Baseline vitamin D levels not associated with treatment outcomes	Chan et al[19], 2015
China CHB (n = 426)	Cross-sectional	NA	< 32 insufficiency ≥ 32 sufficiency	82 18	Vitamin D deficiency common among patients with CHB and associated with adverse clinical outcomes	Wong et al[78], 2015
China CHB (n = 242)	Cross-sectional	NA	< 20: deficiency < 30: insufficiency ≥ 30: sufficiency	8.7 31.4 60	Higher prevalence of vitamin D insufficiency in HBV genotype B patients than in genotype C patients Vitamin D levels not associated with HBV DNA levels or the stage of fibrosis in CHB patients	Yu et al[23], 2015
China CHB (n = 133)	Cross-sectional	NA	< 14: deficiency < 30: insufficiency ≥ 30: sufficiency	27 66.2 6.8	Higher prevalence of vitamin D insufficiency in HBV genotype B patients than in genotype C patients Vitamin D levels not associated with other clinical parameters	Zhu et al[93], 2016
Germany CHB (n = 203)	Cross-sectional	NA	< 10: deficiency < 20: insufficiency ≥ 20: sufficiency	34 47 19	HBV DNA viral loads as strong predictor of low vitamin D levels in CHB patients	Farnik et al[12], 2013
Egypt OBI (n = 16) CHB (n = 52)	Cross-sectional	NA	< 10: deficiency < 30: insufficiency ≥ 30: sufficiency	OBI: 12.5 CHB: 40.4 OBI: 62.5 CHB: 59.6 OBI: 25 CHB: 0	Vitamin D levels significantly higher in OBI than in CHB patients Serum level of vitamin D inversely correlated with HBV DNA loads	Mashaly et al[156], 2016
China CHB (n = 128)	Cross-sectional	NA	< 10: deficiency < 20: insufficiency ≥ 20: sufficiency	13.3 61.7 25	Vitamin D levels negatively correlated with HBV DNA loads Effective antiviral therapy might increase the level of vitamin D in CHB patients	Chen et al[11], 2015
Iran CHB (n = 173)	Cross-sectional	NA	< 10: deficiency < 20: insufficiency ≥ 20: sufficiency	58 39 3	Vitamin D levels inversely correlated with HBV DNA levels	Mohamadkhani et al[89], 2015

CHB: Chronic hepatitis B; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; CLD: Chronic liver disease; OBI: Occult hepatitis B infection; NA: Not applicable.