Association between serum 25(OH) vitamin D, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case–control study

Jb, Wang; Abnet, Christian C.; Chen, Wen; Sm, Dawsey; Fan, Jin‐Hu; Ly, Yin; Yin, Jie; Jm, Major; Pr, Taylor; Qiao, You‐Lin; Freedman, Neal D.

doi:10.1038/bjc.2013.546

Cited by 43 publications

(43 citation statements)

References 37 publications

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“…Although D‑DEF marginally missed significance we could show a trend towards vitamin D status as an independent risk factor for mortality (Table 2). Therefore our results are in line with the results found in previous studies that VIT-D is a valuable predictor for survival [10–13, 27]. We could also show that D‑DEF seems to be a good cut-off for mortality given our Kaplan–Meier curve for all patients (Fig.…”

Section: Discussionsupporting

confidence: 92%

Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis

Paternostro

Wagner

Reiberger

et al. 2016

Wien Klin Wochenschr

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SummaryBackground and aimsVitamin D deficiency is frequent in patients with cirrhosis. The aims of this study were to evaluate the relation of vitamin D status to portal hypertension, degree of liver dysfunction and survival.MethodsPatients with cirrhosis who have been tested for 25-OH-vitamin D levels were retrospectively included. Vitamin D deficiency was defined as 25-OH-vitamin D levels <10 ng/ml. Child–Pugh score, model for end-stage liver disease (MELD) and available hepatic venous pressure gradient (HVPG) were recorded. Mortality was documented during follow-up.ResultsA total of 199 patients were included. Prevalence of vitamin D deficiency (<10 ng/ml) was 40% (79/199), with 14% in Child–Pugh stage A, 39% in Child–Pugh stage B and 47% in Child–Pugh stage C (p = 0.001). Vitamin D deficiency was more common in patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mm Hg) than in patients without (43.5% vs. 24.4%, p = 0.025). Significantly more deaths were observed in patients with vitamin D deficiency (32.9%, 26/79 vs. 13.3%, 16/120; p = 0.001). COX regression found presence of hepatocellular carcinoma (p < 0.001; HR: 5.763 95%CI:2.183–15.213), presence of CSPH (p = 0.026; HR: 5.487 95%CI: 1.226–24.55) and Child–Pugh stage C (p = 0.003; HR:5.429 95%CI: 1.771–16.638) as independent risk factors for mortality. Furthermore we could show a tendency towards group vitamin D deficiency being an independent risk factor (p = 0.060; HR: 1.86 95%CI:0.974–3.552).ConclusionsVitamin D levels progressively decrease in more advanced Child stages and in patients with increasing HVPG. Vitamin D deficiency might be a valuable predictor of mortality in cirrhosis.

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Section: Discussionsupporting

confidence: 92%

Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis

Paternostro

Wagner

Reiberger

et al. 2016

Wien Klin Wochenschr

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“…Collectively, the results of the Skaaby's study confirm and extend the recent work of Wang et al [4] showing an inverse, independent, association between serum 25(OH)D levels and risk of chronic liver disease mortality over 22 years of follow-up among participants of the Linxian Nutrition Intervention Trials. In addition, the results of the Skaaby's study also extend some recent observations from case-control studies suggesting that lower 25(OH)D levels are associated with the presence and severity of NAFLD, independently of several potential confounders, including obesity and other features of the metabolic syndrome [5][6][7][8].…”

supporting

confidence: 82%

Lower 25-hydroxyvitamin D3 levels and increased risk of liver diseases: is there a causal link?

Targher

Byrne

2014

Endocrine

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Vitamin D deficiency is a highly prevalent condition worldwide, reportedly present in approximately 30-60 % of the general adult population [1,2]. This worldwide pandemic remains generally unrecognized and untreated.Vitamin D is critical for bone mineralization, and numerous observational studies have assessed outcomes for skeletal health [1,2].In the past several years, however, attention has turned to non-skeletal effects of vitamin D deficiency or insufficiency. Indeed, the discovery that many extra-renal tissues also possess the vitamin D receptor(s), and the converting enzyme 1a-hydroxylase has provided new insights into the important physiologic paracrine/autocrine roles of vitamin D in various tissues and organs that are mainly dependent on the availability of serum 25-hydroxyvitamin D [25(OH)D] from the circulating plasma [1,2]. Indeed, the presence of nuclear vitamin D receptors in several cell types, including cardiomyocytes, neurons, immune cells, and hepatocytes, has stimulated considerable scientific interest in understanding the putative pleiotropic properties of vitamin D that may regulate hundreds of different genes and play an important role in regulating cell proliferation, differentiation, and apoptosis in many normal and cancer cells and also have anti-inflammatory and immuno-modulatory effects [1,2]. Evolving data indicate that vitamin D deficiency/insufficiency may be playing a role in the pathophysiology of cardiovascular disease as well as several other acute and chronic diseases, including common cancers, autoimmune diseases, osteoarthritis, mental disorders, infectious diseases, metabolic syndrome, and diabetes mellitus [1,2].To our knowledge, the paper published by Skaaby et al. [3] on this issue of the journal is one of the first prospective studies to demonstrate that lower levels of serum 25(OH)D are significantly associated with a higher incidence of fatal and non-fatal liver diseases (as combined endpoint) in a population-based sample of 2,649 middle-aged Danish individuals, who were followed for a median follow-up period of 16.5 years. Diagnosis of incident liver diseases was based on the Danish National Patient Register. Notably, the association between serum 25(OH)D levels and risk of incident liver diseases remained statistically significant after adjusting for age, sex, season measurement, daily alcohol consumption, body mass index, smoking status, leisure time physical activity, dietary habits, education, and serum alanine aminotransferase level. Notably, the number of patients with chronic viral hepatitis was negligible in this cohort (due to a low prevalence of viral hepatitis in Denmark), and the authors have excluded from analysis subjects with cirrhosis or other established liver diseases at baseline in order to reduce the possibility of reverse causation (i.e., lower serum 25(OH)D levels due to liver failure). Unfortunately, however, the authors did not report measurement of serum 1,25-dihydroxyvitamin D levels as the active moiety of vitamin D, and also did not adjust...

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“…In contrast, pooled analyses to assess potential associations between vitamin D status and the seven rarer cancers (not including HCC) found no evidence of a protective effect . Existing data on HCC are scarce, with only one epidemiologic study to date showing a nonstatistically significant inverse association with HCC risk, and a strong inverse association with chronic liver disease mortality . The study was nested within the Linxian Nutrition Intervention Trial cohorts which were conducted in China among poorly nourished and micronutrient‐depleted individuals residing in a region of elevated HCC incidence due to high prevalence of HBV/HCV infections and aflatoxin exposures.…”

mentioning

confidence: 99%

Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study

et al. 2014

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The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n 5 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR 5 0.51, 95% confidence interval [CI], 0.26 to 0.99; P trend 5 0.04; per 10 nmol/L increase: IRR 5 0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required.

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Association between serum 25(OH) vitamin D, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case–control study

Cited by 43 publications

References 37 publications

Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis

Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis

Lower 25-hydroxyvitamin D3 levels and increased risk of liver diseases: is there a causal link?

Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study

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