RESUMO
Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.
RESUMO
INTRODUCTION: The objective of the study was to determine the association of host human leukocyte antigen (HLA) class II genotype DRB1 alleles with the response to interferon therapy, viral loads and extent of liver fibrosis in a group of Romanian patients diagnosed with chronic hepatitis C, with different clinical outcomes. Class II HLA genes, particularly the HLA-DRB1 and DQB1 genes, have been shown to have an important role in self-limiting or persistent viral infection, in different genetic populations. In chronic hepatitis C both susceptible and protective alleles have been described, influencing the development of autoimmunity and progression to cirrhosis and hepatocellular carcinoma. METHODS: The study included 54 patients diagnosed with chronic hepatitis C, registered and monitored from January 2014 to January 2015 at the Clinical Hospital of Infectious Diseases, Constanta, Romania. The selected patients were positive for anti-HCV antibodies and HCV-RNA, with screening laboratory results indicating HCV genotype 1b. The method used for the assignment of alleles at HLA-DRB1 and DQB1 loci was molecular genotyping, by the sequence specific oligonucleotide (SSO) hybridization method, and when required, by the sequence specific primers method (SSP). The presence of different alleles in patients has been analyzed for statistical significance. RESULTS: The presence of HLA-DRB1*0301 had a high frequency (14.8%) in null-responders (NR) while alleles DRB1*0701 (11.1%), DRB1*11# (22.2%) and DRB1*0101 (16.7%) were prevalent in sustained virologic responders (SVR). No significant correlation was found between the presence of HLA-DRB1* alleles and viral loads or liver fibrosis with p values not statistically significant after the Bonferroni correction. CONCLUSION: The presented data suggest that in this group of Romanian patients, certain HLA alleles influence the therapeutic response in HCV infection and genetic predisposition may play a role in hepatitis C virus infection in those patients.
