Sunday, February 19, 2017

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

Systematic Review
World J Hepatol. Feb 18, 2017; 9(5): 278-287
Published online Feb 18, 2017. doi: 10.4254/WJH.v9.i5.278

Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data
Alia S Dadabhai, Behnam Saberi, Katie Lobner, Russell T Shinohara, Gerard E Mullin

Core tip: Vitamin D levels are associated with more advanced fibrosis in chronic hepatitis C

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.

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.

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.

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

Hepatitis C virus (HCV) infection remains one of the most common etiologies of liver disease worldwide. A number of epidemiological papers have addressed the global prevalence of Hepatitis C. Lanini et al[1] reported that 100 million people globally have serological evidence of current or past HCV infection causing 700000 deaths annually while others suggest that the actual occurrence is double[2]. HCV remains the most common indication for liver transplantation in the United States[3]. Chronic infection with HCV can lead to liver inflammation, liver fibrosis, cirrhosis, and hepatocellular carcinoma.

Liver fibrosis is a result of excessive accumulation of extracellular matrix proteins, as part of the wound healing response to chronic injury and chronic inflammation[4]. Various factors have been associated with progression of fibrosis including duration of infection, age, male sex, diabetes, alcohol consumption and human immunodeficiency virus (HIV) co-infection[5].

Vitamin D is a hormone that has numerous biological properties that influence host physiology by regulating epigenetic regulation of more than 2000 genes throughout the body. Vitamin D is best known for its role in maintaining bone mineralization but has diverse and profound influences which can determine disease development and outcome. Although referred to as a vitamin, this steroid hormone is synthesized in the body by a series of hydroxylation reactions that occur in skin (7-hydroxylation), the liver (25-hydroxylation) and the kidney (1-hydroxylation)[6] (Figure 1). Reduction of the enzymatic conversion of 7-dehydrocholesterol to 1.25 hydroxy vitamin D at any of the three conversion steps can result in suboptimal vitamin D status[7].

Vitamin D has a number of influences on innate and adaptive immunity which are pertinent to study in conditions that are driven by chronic inflammation and maladaptive tissue injury[8,9]. Given the ubiquitous distribution of vitamin D receptors in virtually every cell in the body-suboptimal vitamin D status has been studied for its relationship to numerous diseases[10].

For example, there is substantial evidence that vitamin D benefits rheumatoid arthritis, due to its immunomodulatory effect[11]. The role of vitamin D in various cancers has been established linked to its antiproliferative action mediated through vitamin D nuclear receptor[12]. There have been numerous reports on lower serum vitamin D levels in patients with chronic liver disease from various etiologies[13]. In chronic HCV, Low vitamin D levels have been reported in 46% to 92% of patients[10] raising suspicion of its potential contribution to disease pathogenesis.

There is growing evidence from various groups, that vitamin D levels are inversely correlated with liver inflammation and stage of liver fibrosis in patients with HCV; however, the studies are heterogeneous with occasionally the results are conflicting. Additionally, the methods of reporting liver fibrosis were variable.

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].

The aim of this study was to evaluate the relationship between vitamin D status and hepatic fibrosis based on histopathological staging in patients with chronic HCV mono-infection or co-infected HIV-HCV infection, by performing a systematic review of the scientific literature followed by a meta-analysis.

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Of Interest
January 9, 2017
Is there an association between vitamin D and liver fibrosis in patients with chronic hepatitis C?
This study aimed to evaluate the association between serum vitamin D levels and the histopathological findings in patients with chronic hepatitis C virus infection.

Of the 74 patients included in the study, 45 (60.8%) were women, mean age was 57.03±9.24 years, and 63 (85.1%) were white. No association was observed between the serum levels of vitamin D and inflammatory activity (P=0.699) nor with the degree of liver fibrosis (P=0.269).

In this study, no association was observed between vitamin D and inflammatory activity, as well as the degree of liver fibrosis, in patients with chronic hepatitis C.
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