Martin Janicko

Background: The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. Objectives: The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Design: Cross-sectional observational study. Methods: Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The control group was sampled, matched for age and sex, from the general population obtained from nation wide SIRIUS database, which aims to screen the general population for liver disease. Liver stiffness as a surrogate marker of liver fibrosis was the primary outcome, while achieving complete biochemical response (CBR) was a secondary outcome of our research. Results: Prevalence of MASLD was 42.3% in the PBC group and 41.9% in the control group (NS). Prevalence of MetS was 38.9% in PBC and 60.7% in the control group ( p < 0.001). Advanced liver fibrosis was present significantly more often in the PBC group (21.5%), even after stratification by CBR (9.8%), than in age and sex matched general population (2%; p = 0.003). MetS (odds ratio (OR) 4.561, 95% confidence interval (CI): 1.852–11.398) and the number of fulfilled MetS criteria (1.901, 95% CI: 1.239–2.915), but not MASLD (OR 3.956, 95% CI: 0.730–21.422) were associated with advanced fibrosis. Out of individual MetS criteria hyperglycemia/diabetes mellitus had the strongest association with advanced fibrosis, followed by high-density lipoprotein cholesterol criterion. Neither MASLD nor MetS was associated with CBR. Conclusion: Patients with PBC appear to have a lower prevalence of MetS than age and sex matched general population, despite the same prevalence of MASLD in both groups. MetS but not MASLD was associated with the presence of advanced fibrosis in patients with PBC.

Covert hepatic encephalopathy is a highly prevalent complication of liver failure or portosystemic shunting. However, the current diagnostic methods have not been widely adopted in routine clinical practice due to their time-consuming or technically complex nature. This study aimed to develop and evaluate a clinically feasible machine learning model capable of detecting covert hepatic encephalopathy using features extracted from sustained vowel phonation recordings. The XGBoost model achieved the highest AUROC of 81.20 (95% CI 73.03–89.73) and showed reasonable calibration across the full spectrum of predicted probabilities (Hosmer–Lemeshow p = 0.66). The most influential features indicated that patients with covert hepatic encephalopathy tended to have reduced variation in volume, maintaining more constant and harsher vocal quality.

Fecal microbiota transplantation (FMT) seems to be a promising approach in ulcerative colitis (UC) management with the aim of repopulating a patient’s dysbiotic microbiota with beneficial bacteria and restore its metabolic activity to its healthy characteristics. Metabolites present after FMT may improve the function and integrity of the intestinal barrier, reduce inflammation, and thus induce remission in an UC patient. In this study we evaluated whether the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model may be a suitable non-invasive alternative for studying and modifying the dysbiotic microbiota in UC by FMT application. SHIME® model was used to investigate microbial and metabolic changes in the gut microbiota of UC patient induced by FMT application. FMT-modified metabolites from SHIME® were applied to an in vitro model of the intestinal barrier (differentiated Caco-2 and HT-29-MTX-E12 cell lines) compromised by pro-inflammatory cytokines to study the effect of FMT on the intestinal barrier. Qualitative and quantitative microbial analyses showed that FMT increased the diversity and variability of the microbiota in UC patient associated with a significant increase in total bacteria, Bacteroidota and Lactobacillus, as well as an increase in butyrate levels. In addition, an increase in the relative abundance of some important species such as Faecalibacterium prausnitzii and Bifidobacterium longum was observed, and there was also an enrichment of the microbiota with new species such as Blautia obeum, Roseburia faecis, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans and Eubacterium rectale. Furthermore, microbial metabolites modulated by FMT from the SHIME® model prevented intestinal barrier damage and inhibited interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) secretion when cell barriers were pretreated with FMT medium for 24 h. In summary, this study confirmed that a single dose of FMT beneficially modulated the composition and metabolic activity of the UC microbiota in the SHIME® model. FMT favorably modulates the gut microbiota of UC patient cultured in the SHIME® model. FMT-modulated SHIME-derived microbial metabolites improve intact and inflamed intestinal barrier properties in vitro. Repeated applications are necessary to maintain the beneficial effect of FMT in SHIME® model.

Objectives: The aim of this study was to confirm the effectiveness of FMT on the basis of optimum composition of the faecal microbiota of the donor for support therapy in patients with ulcerative colitis, and to observe the viability of the microbiota in frozen and lyophilised administration forms of FMT under various storage conditions. Methods: The bacterial microbiota composition of the FMT samples was assessed using amplicon sequencing via next-generation sequencing (NGS) technology, conducted on the Illumina MiSeq platform. The BD FACS Canto flow cytometer was used to analyse the metabolic activity of FMT samples. Results: FMT analysis confirmed the presence of key butyrate-producing organisms, specifically highlighting species such as Bifidobacterium adolescentis, Faecalibacterium prausnitzi, Coprococcus catus, Eubacterium rectale, alongside contributions from genera Roseburia and Blautia. These organisms play a crucial role in maintaining intestinal health in humans. The viable microorganism counts were significantly higher (p < 0.001) in the frozen form of FMT (−70 °C) in comparison to lyophilised forms (−70 °C, 4 °C and 20 °C) throughout the storage period. Conclusion: The conducted NGS analyses allowed us to confirm the suitability of our FMT donor as a potential candidate for the target group of patients diagnosed with ulcerative colitis. From the point of view of optimum utilisation of FMT at its highest metabolic activity for the purpose of transplantation, its storage for a maximum of 2 months under specified conditions was confirmed as the most suitable for the frozen and all lyophilised FMT forms.

In this review article, we summarize the most common clinical manifestations of Primary biliary cholangitis (PBC): pruritus, fatigue, osteoporosis, and dyslipoproteinemia and discuss their impact of the patients’ quality of life. More than half of PBC patients suffer from pruritus or fatigue at the time of diagnosis. We discuss the pathophysiological aspects of the PBC clinical manifestations and treatment options. The pathophysiology of pruritus and fatigue is not adequately elucidated, but IL-31 is associated with the severity of pruritus and could be used to objectify the subjective reporting by questionnaires. Although PBC patients suffer from atherogenic dyslipidemia, they do not seem to have a higher cardiovascular risk; however, this observation needs to be clarified by further clinical studies. The second-line of PBC treatment affects pruritus severity: Obeticholic acid (OCA) worsens pruritus while fibrates improve it. Itching can be alleviated by both non-pharmacological and pharmacological approach, however the are multiple barriers to pharmacological treatment. There is no adequate treatment for fatigue today. Treatment of osteoporosis and dyslipidemia is similar for non-PBC patients; stage of liver disease should be considered in treatment. Further research to clarify the pathophysiology and to eventually discover an effective treatment to improve survival and quality of life (especially pruritus and fatigue) in PBC patients is needed.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease characterized by the destruction of the small intrahepatic bile ducts, which can progress to liver cirrhosis. The gold standard in the treatment of PBC is ursodeoxycholic acid (UDCA), which is indicated in all patients with PBC because it improves not only biochemical parameters but also patients’ survival. An important milestone in the identification of patients at risk is the assessment of biochemical response to UDCA. Patients who respond to treatment have a lower incidence of hepatic events and better prognosis than patients who do not. Several scoring systems can be used to assess the response and identify non-responders who will benefit from second-line treatment. Obeticholic acid (OCA) is currently the only approved second-line treatment for PBC, which is effective for non-responders to UDCA therapy or patients, who have not tolerated UDCA therapy. However, OCA is contraindicated in advanced liver cirrhosis and portal hypertension. Moreover, pruritus may be a limiting factor for the administration of OCA. Fibrates have shown promising data supporting their use in non-responders to UDCA because they improve the biochemical parameters and elastographic findings and have possible antipruritic effects. Therefore, the idea of a triple treatment seems interesting. Clinical research is focusing on several other groups of drugs: peroxisome proliferator-activated receptor (PPAR) δ- and α/δ agonists, non-steroidal farnesoid X receptor agonists, fibroblast growth factor 19 modulators, and inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4.

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.

The overall prevalence of hyponatremia in cirrhotics is around 50%. Hypovolemic hyponatremia is a result of excessive fluid loss caused mostly by diuretic treatment or diarrhea. More common is hypervolemic hyponatremia, which results from excessive activation of water and sodium-retaining mechanisms caused by effective arterial hypovolemia. This review focuses on the associations of hyponatremia with clinical outcomes and reviews the available data on its management. Hyponatremia is a strong predictor of mortality and is also associated with an increased probability of hepatorenal syndrome, disturbance of consciousness, infections, and unfavorable post-transplant outcomes. In the management of hyponatremia, it is crucial to distinguish between hypovolemic and hypervolemic hyponatremia. The treatment of hypervolemic hyponatremia should be started only in symptomatic patients. The cessation of the treatment with traditional diuretics and fluid restriction may prevent further decrease in natremia. Pharmacological treatment is directed towards cirrhosis itself, precipitating factor, or hyponatremia directly. Currently, only albumin infusions can be recommended routinely. Other possibilities, such as vaptans, splanchnic vasoconstrictors, niravoline, or osmotic diuretics, are restricted to specific use cases (e.g., imminent liver transplantation) or need more research to determine their efficacy. We tried to summarize the management of hyponatremia into a concise flowchart.

Hepatocellular carcinoma (HCC) has multiple molecular classes that are associated with distinct etiologies and, besides particular molecular characteristics, that also differ in clinical aspects. We aim to characterize the clinical aspects of alcoholic liver disease-related HCC by a retrospective observational study that included all consequent patients diagnosed with MRI or histologically verified HCC in participating centers from 2010 to 2016. A total of 429 patients were included in the analysis, of which 412 patients (96%) had cirrhosis at the time of diagnosis. The most common etiologies were alcoholic liver disease (ALD) (48.3%), chronic hepatitis C (14.9%), NAFLD (12.6%), and chronic hepatitis B (10%). Patients with ALD-related HCC were more commonly males, more commonly had cirrhosis that was in more advanced stages, and had poorer performance status. Despite these results, no differences were observed in the overall (median 8.1 vs. 8.5 months) and progression-free survival (median 4.9 vs. 5.7 months). ALD-HCC patients within BCLC stage 0–A less frequently received potentially curative treatment as compared to the control HCC patients (62.2% vs. 87.5%, p = 0.017); and in patients with ALD-HCC liver function (MELD score) seemed to have a stronger influence on the prognosis compared to the control group HCC. Systemic inflammatory indexes were strongly associated with survival in the whole cohort. In conclusion, alcoholic liver disease is the most common cause of hepatocellular carcinoma in Slovakia, accounting for almost 50% of cases; and patients with ALD-related HCC more commonly had cirrhosis that was in more advanced stages and had poorer performance status, although no difference in survival between ALD-related and other etiology-related HCC was observed.