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

Abstract

Aim: To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients.

Methods: Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis.

Results: The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies.

Conclusion: Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.

Keywords: Chronic hepatitis C; Hepatitis C virus; Liver fibrosis; Vitamin D.

Figure 1

Vitamin D metabolism. Vitamin D has diverse influences throughout the body as vitamin D receptors present on virtually every cell. The actions of vitamin D can be subdivided into two larger categories: Calcemic and non-calcemic actions. The non-calcemic actions of vitamin D are legion and have been reviewed elsewhere[6,54-58]. Reproduced with permission[6].

Figure 2

Flowchart of study selection process. Eighteen hundred and twelve articles were identified using PubMed (n = 468)/EMBASE (n = 1269)/Cochrane (n = 23)/Scopus (n = 42)/LILACS (n = 10) search engines. Detailed evaluation of the articles by at least two independent reviewers (total of three) narrowed the studies to twelve (n = 2521) based upon inclusion and exclusion criteria as listed in Table 1.

Figure 3

Meta-analysis of the pooled data from the 12 included studies. The odds ratio for severe fibrosis comparing low vitamin D levels was estimated by meta-analyzing studies including a total of 2521 patients. Details concerning the analytic strategy are provided in the Materials and Methods section.