Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data

Table 1 Pooled data of vitamin D levels and liver fibrosis from the 12 included studies

Year	Author	Country	Design	n	HCV GT	HIV	Definition of vitamin D insufficiency (I)/deficiency (D)	Outcome (serum vitamin D and liver fibrosis)	P value/OR 95%CI	GRADE quality of evidence very low = 1, low = 2, moderate = 3, high = 4 and strength of recommendation: 2 = strong 1 = weak
2010	Petta	Italy	Prospective	197	1	No	< 30 ng/mL for low vitamin D level	Low 25(OH)D associated with severe fibrosis (F3/F4)	0.942 [0.893, 0.994] P = 0.009	GRADE 3
										Strong
2011	Terrier	France	Prospective	189	1,-4 other	Yes	< 10 ng/mL D, 10-30 ng/mL (I)	Low 25(OH)D correlate with severe fibrosis (F3/F4)	P = 0.04	GRADE 3
										Strong
2012	Lange	Sweden	Retrospective	496	1, 4	No	< 10 ng/mL D, < 20 ng/mL (I)	Advanced fibrosis stage F2-F4 vs F0-F1 associated with low 25(OH)D	0.31 [0.12, 0.82] P = 0.018	GRADE 2
										Weak
2012	Weintraub	United States	Cross-sectional	171	1	No	< 20 ng/mL or < 30 ng/mL (I)	Higher 25(OH)D predictive of milder fibrosis (F0-F2) in white patients but not in African Americans	P = 0.007	GRADE 2
										Weak
2012	Baur	Switzerland	Cohort	251	1, 3	No	< 20 ng/mL (I)	(1) 25(OH)D lower in more advanced fibrosis (F2 vs F0-1); (2) low 25-OH vitamin D associated with rapid fibrosis progression rate.	P = 0.005,	GRADE 3
									P = 0.013
										Strong
2013	El-Maouche	United States	Prospective	116	-	Yes	< 15 ng/mL (D)	(1) The prevalence of significant fibrosis (F2 ≥ 2) was similar among those with and without low	P = 0.43	GRADE 3
								Vitamin D; (2) low 25(OH)D not associated with significant fibrosis after adjusting for other confounders	1.37 [0.77, 2.44]
2013	Mandorfer	Austria	Prospective	65	1, 4	Yes	< 10 ng/mL D, 10-30 ng/mL (I)	Patients with	P = 0.009	Strong
								D-DEF displayed a higher prevalence of advanced liver		GRADE 3
2013	Kitson	Australia and New Zealand	Prospective	274	1	No	< 50 nmol/L D < 75 nmol/L (I)	Fibrosis than patients with D-NORM Baseline 25(OH)D level did not vary with fibrosis stage (F3/4 vs F0-2)	P = 0.18	Strong
										GRADE 3
2013	Amanzada	Germany	Prospective	191	1	Yes	< 30 ng/mL (I)	Low 25(OH)D associated with advance fibrosis (F0-2 vs F3/4)	P = 0.02	Strong
										GRADE 3
2014	Gerova	Bulgaria	Retrospective	296	1, 4	No	< 25 nmol/L (D), 25-50 nmol/L for profound (I), 50 –80 nmol/L for mild (I)	Lower 25OHD levels were registered in cases with advanced fibrosis compared to those with mild or absent fibrosis	P >0.05	Strong
										GRADE 2
2014	Guzman-Fulgencio	Spain	Retrospective	174	1, 4	Yes	< 10 ng/mL (D), 10-30 ng/mL (I)	Low 25(OH)D deficiency associated with advanced fibrosis (F3/4 vs F0-2)	P = 0.005	Weak
										GRADE 2
2015	Esmat	Egypt	Prospective	101	4	No	< 20 ng/mL (D), 20-30 (I)	No correlation found between vitamin D levels and stage of liver fibrosis	P = 0.26	Weak
										GRADE 3

HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; GRADE: Grading of Recommendations Assessment, Development and Evaluation.

Table 2 Selection criteria for inclusion and exclusion

Inclusion criteria

Age ≥ 18 yr

Studies including mono-infected HCV or co-infected HCV/HIV

Studies that evaluated liver fibrosis stage, only based on liver histology

Studies that reported serum or plasma 25(OH)D levels

Exclusion criteria

Age < 18 yr

Other etiologies of liver disease, other than hepatitis C

Studies that used non-invasive methods in evaluating liver fibrosis

Inadequate data

HCV: Hepatitis C virus; HIV: Human immunodeficiency virus.