Aim of the study:It has long been a focus of research to differentiate among the various causes of neonatal cholestasis, particularly biliary atresia (BA) from non-BA. The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome's role in the pathophysiology of BA is becoming increasingly clear. However, animal models served as the foundation for most of this research. As it is important to diagnose BA as early as possible for a favorable prognosis, the current investigation aimed to investigate the function of NLRP3 rs10754558 and NLRP3 gene expression level in distinguishing BA from non-BA. Material and methods:The study included 21 patients with BA, 24 patients with neonatal cholestasis due to causes other than BA, and 20 healthy infants as the control group. A clinical evaluation and standard laboratory testing were conducted on each participant. NLRP3 rs10754558 and NLRP3 gene expression level were measured using TaqMan allelic discrimination assay and quantitative real-time polymerase chain reaction (PCR), respectively. Results:A significant difference in NLRP3 rs10754558 was observed between the BA and non-BA groups in the general genotype model (p = 0.048) and the overdominant model (p = 0.012). However, there was no discernible variation in the levels of NLRP3 gene expression between the two groups. In non-BA patients, there was a negative association between the international normalized ratio (INR) and expression of the NLRP3 gene. No correlation was found between NLRP3 expression and liver inflammation and fibrosis, nor between NLRP3 rs10754558 and NLRP3 expression. Conclusions:In conclusion, NLRP3 rs10754558 may contribute to non-BA neonatal cholestasis in ways other than by influencing gene expression levels. However, in non-BA patients, NLRP3 expression levels may improve coagulation.
This review paper discusses the pathogenesis, classification, and principles of prevention and treatment of portal hypertension, with particular emphasis on gastric varices. Gastric varices are less common than esophageal varices, but have distinct pathophysiology, classification, and management strategies, which justifies presenting them separately from other varices. The topics covered are based on the Baveno VII consensus, recommendations and findings from studies conducted in other countries, as well as on the authors’ own clinical experience. This paper is an expanded and updated version of the article published in Hepatologia (2025; 25: 96-101).
Aim of the study:Alpha-fetoprotein (AFP) is the most widely used marker of hepatocellular carcinoma (HCC). Betatrophin is a hormonal protein secreted by the liver and adipose tissue, with metabolic and antiproliferative functions. The aim of this study was to evaluate the betatrophin concentration in patients with HCC and liver cirrhosis. Material and methods:The study enrolled 96 patients with HCC (group 1), 81 with cirrhosis (group 2), and 13 with non-advanced liver disease (group 3, control). Betatrophin levels were tested using the ELISA test (AVISCERA BIOSCIENCE). The Mann-Whitney U-test, the Kruskal-Wallis test, and Spearman's correlation were used in the statistical analysis. Results:Group 1 comprised 71 men and 25 women with a mean age of 61.5 years. Group 2 consisted of 57 men and 24 women with a mean age of 58.5 years. The control group included 7 men and 6 women, with a mean age of 46 years. The median AFP level in group 1 was 393 ng/ml and the betatrophin level was 25 ng/ml. In group 2, AFP averaged 4.5 ng/ml, and betatrophin was 21.9 ng/ml. In group 3, AFP was 3.6 ng/ml, and betatrophin was 7.6 ng/ml. The optimal betatrophin threshold for predicting HCC was established at 30.23 ng/ml, with sensitivity of 64.0%, specificity of 62.5%, PPV of 37.2%, and NPV of 83.3%. ROC curves were assessed using the DeLong method. Betatrophin (AUC = 0.642, p = 0.0326) showed significantly better performance than AFP (AUC = 0.584, p = 0.117) in detecting HCC in women. Conclusions:Betatrophin is a promising diagnostic marker for HCC in cirrhotic patients, particularly women.
The Visegrad Group - the Czech Republic, Hungary, Poland and Slovakia - face shared challenges in preventing and controlling viral hepatitis. A regional meeting convened by the Viral Hepatitis Prevention Board evaluated health systems, epidemiology, and national policies, revealing accomplishments and needs for prevention, screening, diagnosis, and linkage to care of viral hepatitis. Universal hepatitis B (HBV) vaccination exists, yet vaccine hesitancy and incomplete coverage threaten progress, while surveillance and registries remain fragmented. Access to hepatitis C (HCV) treatment has improved recently, but remains centralized, with limited engagement of marginalized populations. Elimination of HCV by 2030 is unlikely due to insufficient screening, COVID-19-related healthcare disruptions, and weak political commitment, whereas HBV control depends on maintaining high vaccination coverage and robust monitoring. Participants called for harmonized national guidelines, strengthened regional collaboration, and sustainable action plans backed up by political commitment. Urgent, coordinated efforts are needed to achieve the WHO 2030 elimination goals.
Aim of the study:Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advances in therapy, the prognosis remains poor, highlighting the need for novel, low-toxicity therapeutic strategies. Campesterol, a naturally occurring dietary phytosterol, has been reported to exert anti-proliferative and pro-apoptotic effects in various cancers, yet its activity in liver cancer cells remains underexplored. Material and methods:The anticancer potential of campesterol was evaluated in human hepatocellular carcinoma (HepG2) cells. Cells were treated with increasing concentrations of campesterol (10, 50, 100, and 200 μg/ml) for 24 h. Cell viability and proliferation were assessed by MTT and crystal violet assays, while cell death was quantified by trypan blue exclusion. Data were analysed using one-way ANOVA followed by Tukey's post-hoc test, with p < 0.05 considered significant. Results:Campesterol exhibited a dose-dependent effect on HepG2 cells. No significant change in viability was observed at lower concentrations (10-100 μg/ml), whereas a marked reduction in cell viability and increase in cell death were detected at 200 μg/ml (p < 0.05). Findings were consistent across MTT, crystal violet, and trypan blue assays, supporting the concept of apoptosis-associated cytotoxicity. Conclusions:These findings demonstrate that campesterol reduces viability and promotes apoptosis in HepG2 cells, suggesting its potential as a low-toxicity adjunct in HCC therapy. Further mechanistic investigations and in vivo studies are warranted to validate its translational applicability.
Aim of the study:Delays in diagnostic paracentesis for suspected spontaneous bacterial peritonitis (SBP) contribute to preventable mortality in cirrhosis. This study aimed to develop and internally validate a pragmatic bedside score using routinely available admission variables to stratify the risk of SBP at hospital presentation. Material and methods:In this retrospective single-center cohort study, 1,312 consecutive adults with cirrhosis and ascites admitted between January 2020 and January 2025 were screened. A total of 1,000 unique patients met the eligibility criteria and were randomly divided into derivation (n = 700) and validation (n = 300) cohorts. SBP was defined as an ascitic polymorphonuclear leukocyte count ≥ 250/mm3. Multivariable logistic regression was used to identify independent predictors, which were incorporated into a four-component bedside score (SCAN: serum sodium, C-reactive protein, age, and neutrophil-to-lymphocyte ratio). Model discrimination and calibration were assessed. Results:Spontaneous bacterial peritonitis was diagnosed in 185 patients (18.5%). In the validation cohort, the SCAN score demonstrated good discriminatory performance (AUROC 0.91, 95% CI: 0.87-0.94) and acceptable calibration (slope 0.96, Brier score 0.06). The probability of SBP increased progressively from 2.2% at a score of 0 to 75.0% at scores of 5-6. A prespecified cut-off of ≥ 3 points yielded a sensitivity of 88.1% and a specificity of 91.7%. Conclusions:The SCAN score is a simple bedside tool that stratifies the risk of spontaneous bacterial peritonitis using routine admission variables. It may assist clinicians in prioritizing timely diagnostic evaluation, complementing guideline-recommended management. Prospective multicenter validation studies are warranted.
Aim of the study:Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in developed countries. Older adults may be prone to symptomatic disease due to age-related vulnerability or underlying conditions. Limited data exist regarding risk factors, clinical outcomes, and liver fibrosis markers in elderly populations. Material and methods:We conducted a single-center retrospective review between January 1, 2016, and March 31, 2025. Patients diagnosed with acute HEV infection were included. The FIB-4 index was calculated 3-6 months after clinical recovery and used as a descriptive, exploratory indicator rather than a diagnostic test. Results:Eight patients met the inclusion criteria, with a median age of 68 years (IQR: 63.5-70.5); six (75%) were male. One asymptomatic case was identified through routine blood donor screening. Comorbidities included hypertension (n = 3) and diabetes mellitus (n = 1). Two patients reported regular alcohol consumption. Among symptomatic patients, the median FIB-4 index was 2.00 (IQR: 1.65-3.08), compared to 1.61 in the asymptomatic patient. Six patients required hospitalization for a median of 17.5 days (IQR: 12-27). One patient received steroid pulse therapy. All patients recovered, with no progression to chronic hepatitis. Conclusions:In this small cohort, most HEV cases occurred in older men. Post-recovery FIB-4 values were numerically higher among symptomatic cases, but this observation is descriptive and hypothesis-generating; the FIB-4 index should not be used during the acute phase. HEV should be considered in older adults presenting with acute liver dysfunction, regardless of dietary or travel history, and fibrosis assessment - when clinically indicated - should rely on comprehensive noninvasive approaches rather than a single score.
Infections with the liver flukes Clonorchis sinensis and Opisthorchis viverrini are currently endemic in Southeast and East Asia. Their limited ecological and geographical distribution is caused by environmental factors and culinary habits of the human population. Climate change, globalization, increasing human mobility, and environmental changes affecting the reservoir of zoonotic infections may change the epidemiology of trematodes. The species C. sinensis and O. viverrini have been recognized as biological carcinogens leading to the development of biliary tract cancer. This paper presents the epidemiology of infections with the above species, and summarizes the known mechanisms of cholangiocarcinogenesis induced by parasitic invasion.
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by immune-mediated injury to the small intrahepatic bile ducts, culminating in impaired bile flow and, over time, progressive cholestasis, ductopenia, and biliary cirrhosis. Osteoporosis is a systemic skeletal disorder characterized by increased bone fragility, decreased bone mineral density, deterioration of bone microarchitecture, and increased fracture risk. In PBC, the most important risk factor for osteoporosis is disease stage. Elevated serum bilirubin and bile acids observed in PBC exert deleterious effects on osteoblasts, leading to cellular dysfunction and promoting osteoporotic change. The predominant pathogenic mechanism appears to be osteoblast dysfunction with reduced bone formation, although increased bone resorption may also occur in some cases. Management of osteoporosis in PBC includes vitamin D and calcium supplementation, with bisphosphonates commonly employed. Ursodeoxycholic acid may attenuate bone loss indirectly by improving cholestasis and has been reported to enhance osteoblast activity and survival.
Aim of the study:For centuries, silver has been used to combat diseases and to extend the shelf life of food. Today, it is applied in nearly every branch of industry. This study demonstrates the effects of nanosilver on oxidative stress parameters in the liver of rats. Material and methods:The in vivo experiment was conducted on 10-week-old male Fischer 344p rats with initial body weight of 206.0 ±1.65 g. Rats from the control group were administered 0.9% NaCl solution intravenously in the same way as a single dose (group IK), or per os for 28 days (group PK). Results:The route of administration significantly affected glutathione peroxidase activity in both the experimental intervention and control groups (p = 0.0000). When nanoparticles are administered per os, the activity of the enzyme is significantly higher. Glutathione peroxidase (GPx) activity following a single intravenous administration was statistically significantly higher (p ≤ 0.005) in the experimental group compared with the control group. No such relationship was observed for the oral (per os) route of administration. A statistically significant difference in the concentration of carbonyl groups was observed following oral administration, with higher levels in the control group than in the experimental group (p ≤ 0.001). Conclusions:Experimental animal studies indicate that silver nanoparticles are not biologically neutral for living organisms. Depending on the route of administration and the applied dose, nanosilver affects specific enzymes forming the antioxidant barrier, which may lead to disturbances in oxidative balance between reactive oxygen species (ROS) and antioxidants.
The link between lifestyle-related conditions and fatty liver disease has attracted considerable attention in recent years. The number of patients with metabolic dysfunction-associated steatotic liver disease (MASLD), often co-occurring with obesity, diabetes, and dyslipidemia, continues to rise. Accumulating evidence suggests that these conditions synergistically increase the risk of progression to cirrhosis and hepatocellular carcinoma (HCC). Consequently, there is a growing need for testing to identify high-risk liver disease patients based on lifestylerelated conditions, distinct from chronic viral hepatitis or alcohol-induced liver disease, and to determine the most appropriate treatments for these conditions, especially obesity, diabetes, and dyslipidemia. This review outlines the strategy for treating fatty liver disease currently being used in community hospitals, with the goal of reducing HCC and preventing cardiovascular disease.
Aim of the study: Liver fibrosis (LF), cirrhosis, and hepatocellular carcinoma (HCC) are strongly correlated and impose a heavy burden on the global healthcare system. Currently, there are no effective treatments, and thus we performed dual-omics analysis to identify new targets and regulatory mechanisms. Material and methods: A two-sample Mendelian randomization (MR), with cis-expression quantitative trait locus (cis-eQTL) as the genomic variables and cis-protein quantitative trait locus (cis-pQTL) as the proteomic variables, was performed to identify candidate therapeutic targets for LF, cirrhosis, and HCC at the gene and protein levels. Colocalization analysis was performed to screen for significant candidate targets. Moreover, the results were validated using summary-data-based MR (SMR) analysis. To further explore the downstream regulatory mechanisms of the targets, we performed two-step MR, with circulating metabolites, immune cells, gut microbiota, and inflammatory proteins as mediating variables. Results: Through the two-sample MR, we identified 9 candidate targets for LF, 6 targets for cirrhosis, and 12 targets for HCC. Two significant therapeutic targets for LF, 3 targets for cirrhosis, and 1 target for HCC were identified through colocalization analysis. Among them, DMWD, CDK13, ATRAID, SLC5A6, and CD300LD were validated through SMR. Further analysis revealed that ATRAID might inhibit cirrhosis by upregulating threonine levels. In contrast, CDK13 was predicted to promote LF by suppressing CD20 on naive-mature B cells. Conclusions: In this study, dual-omics analysis identified new therapeutic targets for LF, cirrhosis, and HCC, as well as potential regulatory mechanisms; these results lay the foundation for further investigations into the disease mechanisms and new drug development.
The recently observed increase in cardiovascular disease incidence in patients with chronic hepatitis C has contributed to hepatitis C virus (HCV) being considered a new, non-classical risk factor. HCV infection may also lead to the development of metabolic disorders, which play an important role in the development of cardiovascular diseases. The notable impact of HCV on the development of obesity, insulin resistance, diabetes, lipid disorders and fatty liver has led to metabolic disorders in the course of HCV infection being referred to as metabolic-viral syndrome. On the other hand, modern treatment of HCV infection with direct-acting antiviral drugs is extremely effective and safe, while drug interactions are the main potential limitation. This article presents expert recommendations for the diagnosis and treatment of heart disease and lipid disorders in HCV-infected patients.
