Background: Constipation is a common problem in gastroenterological practice. The prevalence of constipation is about 16%. Constipation can be primary or secondary. Summary: The diagnostic and therapeutic approach to patients with constipation begins with a detailed history and physical examination. In selected cases, the use of additional diagnostic procedures is very important. This includes the use of laboratory, endoscopic, and radiological examinations, as well as advanced physiological testing (anorectal manometry, balloon expulsion test, colonic transit studies, and defecography). Constipation therapy can be both nonoperative and operative. Nonoperative therapy includes the application of a lifestyle measures, pharmacotherapy and biofeedback therapy. Key Messages: Two key things when taking a medical history and physical examination are to rule out the existence of alarm symptoms/signs and to rule out secondary constipation (primarily drug-induced). Therapy begins with lifestyle modification, and in case of failure, bulk or osmotic laxatives are used. In case of failure, the use of lubiprostone is indicated, as well as linaclotide. Surgical treatment of constipation is reserved for cases of refractory constipation, with delayed intestinal transit.

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.

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.

Background: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. Summary: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. Key Messages: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

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.

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.