Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis

AIM: To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis. METHODS: We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFR(Cr)) and cystatin C (GFR(Cys)) was calculated. RESULTS: We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (r(s) = 0.527, P lt 0.001). More patients with decreased glomerular filtration rate were identified based on GFR(Cys) than on GFR(Cr) (P lt 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P lt 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (r(s) = 0.607, P lt 0.001). Renal resistive index correlated significantly with cystatin C (r(s) = 0.283, P = 0.028) and showed a negative correlation with GFR(Cys) (r(s) = -0.31, P = 0.016). CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis

The clinical importance of biochemical bone markers in patients with alcoholic and viral liver cirrhosis

Background: Metabolic bone disease in patients with chronic liver disease is called hepatic osteodystrophy and is primarily a sequel to osteopenia/osteoporosis, and rarely secondary to osteomalacia: The aim of this work was to define the influence of vitamin D-3 and parathyroid hormone (PTH) in the pathogenesis of hepatic osteodystrophy, as well as the predictive significance of biochemical bone markers. Methods: This prospective study included 58 male patients with alcoholic (49) and viral (9) cirrhosis. The concentrations of serum vitamin D-3, PTH, osteocalcin and beta-carboxy-terminal cross-linked telopeptide of type I collagen (beta-CTX) were determined. Bone density was measured by dual energy X-ray absorptiometry in the L1 -L4 spinal segment and the femoral neck. Results: Lower bone mineral density (BMD) was measured in 41 patients (70.7%). There was no significant correlation between PTH and vitamin D3 values and T score in the femoral neck (p=0.51; p=0.063) and lumbar spine (p=0.49; 0.064). Also, no significant correlation was found between the osteocalcin values in lumbar spine BMD (p=0.944) and femoral neck (p=0.161), or with beta-CTX values and BMD in the lumbar spine (p=0.347) and femoral neck (p=0.73). Statistically significant difference was confirmed between the stage A osteocalcin (p=0.000) and beta-CTX (p=0.008) values in relation to advanced stages B and C. Conclusions: PTH and vitamin D3 do not influence the development of hepatic osteodystrophy. In patients with cirrhosis, osteocalcin and beta-CTX are not valid indicators of decreased BMD, but their values correlate with the degree of liver insufficiency

Precision Medicine for Hepatocellular Carcinoma: Clinical Perspective

Hepatocellular carcinoma (HCC) is one of the major malignant diseases worldwide, characterized by growing incidence and high mortality rates despite apparent improvements in surveillance programs, diagnostic and treatment procedures, molecular therapies, and numerous research initiatives. Most HCCs occur in patients with liver cirrhosis, and the competing mortality risks from the tumor and the cirrhosis should be considered. Presently, previously identified risk factors, such as hepatitis virus infection, hepatic inflammation and fibrosis, and metabolic syndrome, may be used as chemoprevention targets. The application of precision medicine for HCC management challenges the one-size-fits-all concept; moreover, patients should no longer be treated entirely according to the histology of their tumor but based on molecular targets specific to their tumor biology. Next-generation sequencing emphasizes HCC molecular heterogeneity and aids our comprehension of possible vulnerabilities that can be exploited. Moreover, genetic sequencing as part of a precision medicine concept may work as a promising tool for postoperative cancer monitoring. The use of genetic and epigenetic markers to identify therapeutic vulnerability could change the diagnosis and treatment of HCC, which so far was based on Barcelona clinic liver cancer (BCLC) staging. In daily clinical practice, the shift from a stage-oriented to a therapeutic-oriented approach is needed to direct the choice of HCC treatment toward the potentially most effective option on an individual basis. The important factor in precision medicine is the promotion of patient management based on the individual approach, knowing that the final decision must be approved by a multidisciplinary expert team

MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear. Therefore, the aim of this study was to investigate the association of three MDR1 polymorphisms, C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642), with Serbian IBD patients.A total of 206 IBD patients, 107 Crohn's disease (CD) and 99 ulcerative colitis (UC), and 255 healthy controls were included in the study. All subjects were genotyped using TaqMan SNP genotyping assays. Comparisons between the groups were performed using the Pearson Chi-square test. False discovery rate according to Benjamini-Hochberg procedure was applied to adjust for multiple comparisons.Carriers of T allele of all three MDR1 SNPs were more common in UC patients compared to healthy controls, suggesting predisposing role of T allele of these SNPs in UC pathogenesis. Consistently, TT genotype of C1236T and TTT haplotype were also found more frequently in UC patients. On the other hand, C allele and CC genotype of C1236T and C3435T, as well as G allele and GG genotype of G2677T/A were more frequent in healthy subjects, implying protective role of these variants in UC. Likewise, CGC haplotype and CGC/CGC diplotype were more frequent in controls. Contrary to UC, no statistical difference was observed between CD patients and controls in any of the SNPs analyzed.MDR1 gene variants and haplotypes were associated with UC in Serbian IBD patients, further supporting their potential role in susceptibility to UC

Molecular Aspects of MAFLD—New Insights on Pathogenesis and Treatment

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications

The Importance of Artificial Intelligence in Upper Gastrointestinal Endoscopy

Recently, there has been a growing interest in the application of artificial intelligence (AI) in medicine, especially in specialties where visualization methods are applied. AI is defined as a computer’s ability to achieve human cognitive performance, which is accomplished through enabling computer “learning”. This can be conducted in two ways, as machine learning and deep learning. Deep learning is a complex learning system involving the application of artificial neural networks, whose algorithms imitate the human form of learning. Upper gastrointestinal endoscopy allows examination of the esophagus, stomach and duodenum. In addition to the quality of endoscopic equipment and patient preparation, the performance of upper endoscopy depends on the experience and knowledge of the endoscopist. The application of artificial intelligence in endoscopy refers to computer-aided detection and the more complex computer-aided diagnosis. The application of AI in upper endoscopy is aimed at improving the detection of premalignant and malignant lesions, with special attention on the early detection of dysplasia in Barrett’s esophagus, the early detection of esophageal and stomach cancer and the detection of H. pylori infection. Artificial intelligence reduces the workload of endoscopists, is not influenced by human factors and increases the diagnostic accuracy and quality of endoscopic methods

Allele and genotype frequencies of <i>MDR1</i> SNPs in controls, CD and UC groups.

<p>Allele and genotype frequencies of <i>MDR1</i> SNPs in controls, CD and UC groups.</p

Main clinical characteristics of CD and UC patients.

<p>Main clinical characteristics of CD and UC patients.</p

The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome