Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study

Contains fulltext : 89639.pdf (publisher's version ) (Open Access)BACKGROUND: Alpha-1 antitrypsin (A1AT) deficiency, caused by the Z allele (p.E342K) and S allele (p.E264V) in the SERPINA1 gene, can induce liver and pulmonary disease. Different mechanisms appear to be responsible for the pathogenesis of these divergent disease expressions. The c.-1973T >C polymorphism located in the SERPINA1 promoter region is found more frequent in A1AT deficiency patients with liver disease compared to patients with pulmonary disease, but data are lacking regarding contribution to the development of liver diseases caused by other aetiologies. AIM: To study the prevalence of c.-1973T >C, Z allele and S allele in a cohort of patients with liver disease of various aetiologies compared with healthy controls and to evaluate its effect on disease progression. METHODS: A total of 297 patients with liver disease from various aetiologies and 297 age and gender matched healthy controls were included. The c.-1973T >C polymorphism and Z and S alleles of the SERPINA1 gene were analyzed by real-time PCR. RESULTS: c.-1973T >C was similarly distributed between patients with liver disease of various origins and healthy controls. Furthermore, the distribution of c.-1973T >C was independent from aetiology subgroup. In patients with liver disease mean ages at of onset of liver disease were 44.4, 42.3 and 40.7 years for the c.-1973 T/T, T/C and C/C genotype respectively (NS). S allele heterozygosity was increased in patients with drug induced liver injury (DILI), (OR 4.3; 95%CI 1.1-17.2). CONCLUSION: In our study, c.-1973T >C polymorphism was not a risk factor for liver disease of various aetiologies. In addition, S allele heterozygosity might contribute to the development of DILI

Postoperative infections in cirrhotic patients

An overview of the impairments of immune function present and the type as well as frequency of infections seen in individuals with advanced liver disease is presented. Where data are available, the use of antibiotic prophylaxis to prevent these complications is identified. Physicians and surgeons caring for individuals with advanced liver disease need to be aware of these issues and be vigilant to the recognition, early detection and aggressive treatment of infections in patients with advanced liver disease and particularly cirrhosis of any etiology

Dawn-to-dusk dry fasting decreases circulating inflammatory cytokines in subjects with increased body mass index

Background: The circadian rhythm involves numerous metabolic processes, including sleep/awakening, body temperature regulation, hormone secretion, hepatic function, cellular plasticity, and cytokine release (inflammation), that appear to have a dynamic relationship with all the processes above. Studies have linked various cytokines to the chronic state of low-grade inflammation and oxidative stress in obesity. Dawn-to-dusk dry fasting (DDDF) could alleviate the adverse effects of obesity by decreasing inflammation. This study examined the effects of DDDF on circulating inflammatory cytokines in subjects with increased body mass index (BMI). Methods: The current observational prospective study included adult subjects with a BMI equal to or greater than 25 kg/m2 who practiced the annual religious 30-day DDDF. Individuals with significant underlying medical conditions were excluded to limit confounding factors. All subjects were evaluated within two weeks before 30-day DDDF, within the fourth week of 30-day DDDF, and within two weeks after 30-day DDDF. Multiple cytokines and clinical health indicators were measured at each evaluation. Results: Thirteen subjects (10 men and three women) with a mean age of 32.9 years (SD = 9.7 years) and a mean BMI of 32 kg/m2 (SD = 4.6 kg/m2) were included. An overall associated decrease in the levels of multiple cytokines with DDDF was observed. A significant decrease in the mean interleukin 1 beta level was observed within the fourth week of 30-day DDDF (P = 0.045), which persisted even after the fasting period (P = 0.024). There was also a significant decrease in the mean levels of interleukin 15 (IL-15) (P = 0.014), interleukin 1 receptor antagonist (P = 0.041), macrophage-derived chemokine (MDC) (P = 0.013), and monokine induced by interferon gamma/chemokine (C-X-C motif) ligand 9 (P = 0.027) within the fourth week of 30-day DDDF and in the mean levels of fibroblast growth factor 2 (P = 0.010), interleukin 12 p40 subunit (P = 0.038), interleukin 22 (P = 0.025) and tumor necrosis factor alpha (P = 0.046) within two weeks after 30-DDDF. In terms of anthropometric parameters, there was a decrease in mean body weight (P = 0.032), BMI (P = 0.028), and hip circumference (P = 0.007) within the fourth week of 30-day DDDF and a decrease in mean weight (P = 0.026), BMI (P = 0.033) and hip circumference (P = 0.016) within two weeks after 30-day DDDF compared with the levels measured within two weeks before 30-day DDDF. Although there was no significant correlation between changes in weight and changes in circulating inflammatory cytokines, there was a significant positive correlation between changes in waist circumference and changes in specific inflammatory cytokines (e.g., IL-15, MDC, platelet-derived growth factor, soluble CD40L, vascular endothelial growth factor A) within the fourth week of 30-day DDDF and/or two weeks after 30-day DDDF. A significant decrease in mean average resting heart rate within the fourth week of 30-day DDDF was also observed (P = 0.023), and changes between average resting heart rate and changes in interleukin-8 levels within the fourth week of 30-day DDDF compared with baseline levels were positively correlated (r = 0.57, P = 0.042). Conclusion: DDDF appears to be a unique and potent treatment to reduce low-grade chronic inflammation caused by obesity and visceral adiposity. Further studies with more extended follow-up periods are warranted to investigate the long-term anti-inflammatory benefits of DDDF in individuals with increased BMI