Prophylaxis of bacterial infections in cirrhosis: Is an optimal 25-OH vitamin D level required?
Authors: Rodolphe Anty, Quentin M. Anstee, Philippe Gual, Albert Tran
Journal: Journal of Hepatology (2014)

Bacterial infections in cirrhosis: A position statement based on the EASL Special Conference 2013Journal of HepatologyVol. 60Issue 6PreviewBacterial infections are very common and represent one of the most important reasons of progression of liver failure, development of liver-related complications, and mortality in patients with cirrhosis. In fact, bacterial infections may be a triggering factor for the occurrence of gastrointestinal bleeding, hypervolemic hyponatremia, hepatic encephalopathy, kidney failure, and development of acute-on-chronic liver failure. Moreover, infections are a very common cause of repeated hospitalizations, impaired health-related quality of life, and increased healthcare costs in cirrhosis. Full-Text PDF Open Access We read with interest the position statement based on the EASL special conference 2013 dealing with “Bacterial infections in cirrhosis” [[1]Jalan R. Fernandez J. Wiest R. Schnabl B. Moreau R. Angeli P. et al.Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013.J Hepatol. 2014; 60: 1310-1324Abstract Full Text Full Text PDF PubMed Scopus (613) Google Scholar]. Infections in cirrhotic patients are a major problem, both in terms of the high frequency and also the relative high risk of associated mortality. Whilst there has already been significant progress, greater knowledge of the pathophysiology and improvements in the management of these patients are still crucial. Among the parameters associated with a risk of infection, those that can be readily addressed during management are of particular interest. Among them gastrointestinal bleeding, the severity of the liver insufficiency, low protein ascites and a previous episode of infection are clinical situations that may justify a primary or a secondary prophylaxis [[1]Jalan R. Fernandez J. Wiest R. Schnabl B. Moreau R. Angeli P. et al.Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013.J Hepatol. 2014; 60: 1310-1324Abstract Full Text Full Text PDF PubMed Scopus (613) Google Scholar]. Randomized control trials, testing some of these strategies, are in progress (for example, the interest of norfloxacin in the primary prophylaxis against SBP in patients with ascites, NCT01037959). We also wish to highlight another recently described risk factor that should be sought by hepatologists, vitamin D deficiency (<10 ng/ml). We have recently published data that demonstrate an association between severe deficiency in vitamin D and occurrence of bacterial infection in cirrhotic patients, independent of the severity of the liver insufficiency, assessed by the Child-Pugh or MELD score [[2]Anty R. Tonohouan M. Ferrari-Panaia P. Piche T. Pariente A. Anstee Q.M. et al.Low levels of 25-hydroxy vitamin d are independently associated with the risk of bacterial infection in cirrhotic patients.Clin Transl Gastroenterol. 2014; 5: e56Crossref PubMed Scopus (39) Google Scholar]. Whilst causality could not be tested in our prospective observational study, many other studies have also suggested that vitamin D could be implicated in the interactions between the host and bacteria. The anti-bacterial effects of vitamin D may be mediated, but not only through an increase in the innate immune system defence [[3]White J.H. Vitamin D signaling, infectious diseases, and regulation of innate immunity.Infect Immun. 2008; 76: 3837-3843Crossref PubMed Scopus (278) Google Scholar]. The potential link between infections and vitamin D deficiency has also been recently suggested in patients in resuscitation units [[4]Moromizato T. Litonjua A.A. Braun A.B. Gibbons F.K. Giovannucci E. Christopher K.B. Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill.Crit Care Med. 2014; 42: 97-107Crossref PubMed Scopus (138) Google Scholar]. Vitamin D deficiency is frequent in the general population and has been associated with increased mortality [[5]Zittermann A. Iodice S. Pilz S. Grant W.B. Bagnardi V. Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies.Am J Clin Nutr. 2012; 95: 91-100Crossref PubMed Scopus (313) Google Scholar]. Prospective trials of supplementation of vitamin D with calcium in the elderly reduced osteoporotic fractures and mortality [[6]Rejnmark L. Avenell A. Masud T. Anderson F. Meyer H.E. Sanders K.M. et al.Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials.J Clin Endocrinol Metab. 2012; 97: 2670-2681Crossref PubMed Scopus (165) Google Scholar]. Cirrhotic patients also frequently exhibit a deficiency in vitamin D and are exposed to osteoporosis [[7]Guanabens N. Pares A. Liver and bone.Arch Biochem Biophys. 2010; 503: 84-94Crossref PubMed Scopus (52) Google Scholar]. In order to increase bone health in patients with advanced liver disease, experts (including the European Association for the Study of the Liver guidelines for the management of patients suffering from cholestatic liver diseases) suggest a balanced diet and a supplementation with calcium (1000–1500 mg/day) and vitamin D (400–800 IU/day), but little clinical data are available to support this [7Guanabens N. Pares A. Liver and bone.Arch Biochem Biophys. 2010; 503: 84-94Crossref PubMed Scopus (52) Google Scholar, 8European Association for the Study of the Liver EASL Clinical Practice Guidelines: management of cholestatic liver diseases.J Hepatol. 2009; 51: 237-267Abstract Full Text Full Text PDF PubMed Scopus (1388) Google Scholar]. Moreover, alcoholic cirrhotic patients with a severe deficiency in vitamin D (<10 ng/ml) have been suggested to have a higher risk of death [[9]Trepo E. Ouziel R. Pradat P. Momozawa Y. Quertinmont E. Gervy C. et al.Marked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease.J Hepatol. 2013; 59: 344-350Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar]. Vitamin D supplementation in cirrhotic patients could be particularly beneficial in term of morbidity, quality of life and mortality. In conclusion, we suggest that the potential association between vitamin D deficiency and infection in cirrhotic patients should be tested in independent large cohorts to confirm these preliminary data. If validated, a new strategy of supplementation of vitamin D in cirrhotic patients (particularly those with 25-OH vitamin D <10 ng/ml), both to reduce fracture risk and to reduce intercurrent infections, should be tested in randomized control trials. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.