Chronic Liver Pathology Research Articles

A functional genomic framework to elucidate novel causal metabolic dysfunction-associated fatty liver disease genes.

Metabolic dysfunction-associated fatty liver disease (MASLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for MASLD have been hampered by the relative paucity of human data from gold-standard magnetic resonance quantification of hepatic fat. To overcome insufficient sample size, genome-wide association studies using MASLD surrogate phenotypes have been used, but only a small number of loci have been identified to date. In this study, we combined GWAS of MASLD composite surrogate phenotypes with genetic colocalization studies followed by functional in vitro screens to identify bona fide causal genes for MASLD. We used the UK Biobank to explore the associations of our novel MASLD score, and genetic colocalization to prioritize putative causal genes for in vitro validation. We created a functional genomic framework to study MASLD genes in vitro using CRISPRi. Our data identify VKORC1, TNKS, LYPLAL1 and GPAM as regulators of lipid accumulation in hepatocytes and suggest the involvement of VKORC1 in the lipid storage related to the development of MASLD. Complementary genetic and genomic approaches are useful for the identification of MASLD genes. Our data supports VKORC1 as a bona fide MASLD gene. We have established a functional genomic framework to study at scale putative novel MASLD genes from human genetic association studies.

Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling.

The primary cilium, an organelle that protrudes from cell surfaces, is essential for sensing extracellular signals. With disturbed cellular communication and chronic liver pathologies, this organelle's dysfunctions have been linked to disorders, including polycystic liver disease (PLD) and Cholangiocarcinoma (CCA). The goal of this study was to elucidate the relationship between primary cilia and the crucial regulator of cellular proliferation, the epidermal growth factor receptor (EGFR) signaling pathway, which has been associated with various clinical conditions. The study identified aberrant EGFR signaling pathways in cholangiocytes lacking functional primary cilia. Using liver-specific IFT88 knockout mice, a Pkhd1 mutant rat model, and human cell lines that didn't have functional cilia. Cilia-deficient cholangiocytes showed persistent EGFR activation because of impaired receptor degradation, in contrast to their normal counterparts, where EGFR localization to the cilia promotes appropriate signaling. Using HDAC6 inhibitors to restore primary cilia accelerates EGFR degradation, thereby reducing maladaptive signaling. Importantly, experimental intervention with the HDAC6 inhibitor tubastatin A in an orthotopic rat model moved EGFR to cilia and reduced ERK phosphorylation. Concurrent administration of EGFR and HDAC6 inhibitors in cholangiocarcinoma and polycystic liver disease cells demonstrated synergistic anti-proliferative effects, which were associated with the restoration of functioning primary cilia. This study's findings shed light on ciliary function and robust EGFR signaling with slower receptor turnover. We could use therapies that restore the function of primary cilia to treat EGFR-driven diseases in PLD and CCA.

NAFLD is a predictor of high risk of development and a co-factor in the progression of cardiovascular diseases

To date, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver pathology and already at the stage of steatosis causes a high risk of developing cardiovascular diseases (CVD). Convincing evidence has been obtained that CVD is the most common cause of death in patients with NAFLD. Common risk factors (insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease and type 2 diabetes mellitus) and similar pathophysiological mechanisms (endothelial dysfunction, changes in lipid metabolism, systemic inflammation, plaque formation/instability, oxidative stress) of NAFLD and CVD, allow us to consider NAFLD not only as a key risk factor for the development of CVD, but also as a co-factor in the progression of cardiac pathology. The progression of NAFLD itself leads to a more severe course of CVD.

IMPORTANCE OF PHYTOTHERAPY IN CHRONIC NON-INFECTIOUS DISEASES OF THE LIVER

Currently, in the countries of Central Asia, as in most countries, 15-20% of the adult population suffers from acute and chronic liver pathology. Today, non-alcoholic fatty liver disease (NAFLD) is the most common non-communicable liver disease, accounting for approximately 70% of all chronic liver diseases. The complexity and versatility of the pathogenetic mechanisms of lipid metabolism disorders in the body requires effective pharmacological correction aimed at normalizing the composition, structure and ratio of various classes of lipoproteins. In this regard, the most harmless and therapeutically effective herbal remedies of natural origin, metabolic products of plant and animal cells, which have low toxicity and a wide spectrum of action, are of great importance. The advantage of phytotherapy is that it allows the use of plants for a long time without significant side effects, due to their compatibility with many drugs and with each other. KEYWORDS: phytotherapy, herbal remedies, lipid metabolism.

Biophysics-Guided Lead Discovery of HBV Capsid Assembly Modifiers.

Hepatitis B virus (HBV) is the leading cause of chronic liver pathologies worldwide. HBV nucleocapsid, a key structural component, is formed through the self-assembly of the capsid protein units. Therefore, interfering with the self-assembly process is a promising approach for the development of novel antiviral agents. Applied to HBV, this approach has led to several classes of capsid assembly modulators (CAMs). Here, we report structurally novel CAMs with moderate activity and low toxicity, discovered through a biophysics-guided approach combining docking, molecular dynamics simulations, and a series of assays with a particular emphasis on biophysical experiments. Several of the identified compounds induce the formation of aberrant capsids and inhibit HBV DNA replication in vitro, suggesting that they possess modest capsid assembly modulation effects. The synergistic computational and experimental approaches provided key insights that facilitated the identification of compounds with promising activities. The discovery of preclinical CAMs presents opportunities for subsequent optimization efforts, thereby opening new avenues for HBV inhibition.

Insights into the Management of Chronic Hepatitis in Children-From Oxidative Stress to Antioxidant Therapy.

Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60-80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants.

Effect of lipoic acid on the expression of nonalcoholic fatty liver disease-associated genes in the liver of rats fed a hypercaloric choline-deficient diet

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver pathologies. Molecular mechanisms of NAFLD pathogenesis are complex and still require further clarification. Thus, this study aimed to investigate the impact of lipoic acid (LA), widely used as an antioxidant, on the development of different links of NAFLD, including de novo lipogenesis, antioxidant and xenobiotic-metabolizing enzymes by gene expression analysis. The experiment was carried out on three groups of male Wistar rats received control diet, hypercaloric choline-deficient diet (HCCD) or HCCD with LA (HCCD+LA). In the liver of rats the expression of acetyl-CoA carboxylase 1 (Acaca), fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd) and transcriptional regulators sterol-regulatory element-binding protein SREBP (Srebf1), carbohydrate response element-binding protein ChREBP (Mlxipl), peroxisome proliferator-activated receptor alpha PPARα (Ppara), heme oxygenase-1 HO-1 (Hmox1) and nuclear erythroid 2-related factor 2 Nrf2 (Nrf2), cytochrome P450 1A1 CYP1A1 (CYP1A1) and aryl hydrocarbon receptor AhR (AhR), cytochrome P450 2E1 CYP2E1 (CYP2E1) genes were evaluated. Supplementation of HCCD with LA led to an even greater than in HCCD group decrease in Scd gene expression by 88% (p<0.05), as well as a marked suppression of Ppara and Mlxipl by 37% (p<0.05) and 27% (p<0.05), to an 80% (p<0.05) elevation of Hmox1 gene expression relative to the HCCD group, had no pronounced effect on CYP1A1 and AhR gene expression but resulted in a 38% (p<0.05) suppression of CYP2E1 expression compared with that slightly elevated by HCCD. In conclusion, the current study showed that LA reduces lipogenesis de novo, restores the expression of Hmox1 gene of the antioxidant enzyme HO-1, diminished by the HCCD diet, and decreases HCCD-induced level of the expression of CYP2E1 gene of CYP2E1 enzyme, a potential source of free radicals.

Current Understanding of Marginal Grafts in Liver Transplantation.

End-stage liver disease (ESLD), stemming from a spectrum of chronic liver pathologies including chronic liver failure, acute cirrhosis decompensation and hepatocellular carcinoma, imposes a significant global healthcare burden. Liver transplantation (LT) remains the only treatment for ESLD. However, the escalating mortality on transplant waitlists has prompted the utilization of marginal liver grafts in LT procedures. These grafts primarily encompass elderly livers, steatotic livers, livers from donation after circulatory death, split livers and those infected with the hepatitis virus. While the expansion of the donor pool offers promise, it also introduces concomitant risks. These encompass graft failure, biliary and cardiovascular complications, the recurrence of liver disease and reduced patient and graft survival. Consequently, various established strategies, ranging from improved donor-recipient matching to surgical interventions, have emerged to mitigate these risks. This article undertakes a comprehensive assessment of the current landscape, evaluating the viability of diverse marginal liver grafts. Additionally, it synthesizes approaches aimed at enhancing the quality of such marginal liver grafts. The overarching objective is to augment the donor pool and ameliorate the risk factors associated with the shortage of liver grafts.

The importance of nutritional status analysis in the view of dietary aspect in patients with chronic liver diseases

Introduction. Currently, the analysis of the nutritional status represents a rather important topic in the view of various chronic pathologies, especially liver diseases, which currently present a global issue of contemporary medicine. The regulation of eating behavior,and energetic and metabolic disorders present some of the main risk factors for the progression of existing liver disease with evolutionary progression and the development of complications and comorbidities. Materials and methods. A series of scientific publications devoted to the research topic from international databases PubMed, NCBI, etc. were analyzed. Keywordswere created with the adjustment of the selection criteria of the obtained scientific sources written in English, after selecting the filter. Exclusion criteria were proposed with the exclusion of sources without scientific content. Results. The relevant scientific studies of the last 10 years have shown an increased interest in the analysis of the nutritional status of people with chronic liver pathologies. The scientific data analyzed confirms an interrelationship between inadequate food intake and the occurrence of malnutrition. Dysfunctional eating behavior can lead to a number of nutritional problems, which can range from clinical eating disorders such as decreased appetite and others to protein-calorie imbalances that are more pronounced in patients with liver diseases. Conclusions. The analysis of the data demonstrates the need for the non-invasive method, which allows the identification and monitoring of the nutritional status in patients with chronic liver pathologies under the dietary aspect.

Implementation of new technologies in the nutritional assessment of chronic hepatic patients

Introduction. In liver pathology, lipid metabolism is significantly affected. Along with the use of routine laboratory methods for diagnosing nutritional stare and metabolic disorders including dislipidemia, there is a need for simple, accurate and non-invasive methods for assessing body composition, such as bioelectrical impedance analysis (BIA). Materials and methods. There were examined 282 patients with chronic liver pathology, 75 patients with chronic viral hepatitis (HVC group), 96 patients with hepatic steatosis (SH group), 111 patients with liver cirrhosis (CH group). BIA indicators: BMI, percentage of body fat (PBF), indicator of the proportion of visceral fat (PVF) and total cholesterol, HDL, LDL and triglycerides (TG) in serum were determined. Results. BMI in the SH-G was found 30.29±0.50, in the HVC-G - 28.13±0.65, in the CH-G - 22.69±0.16 kg/m². PBF: 36.02±1.06 (SH-G), 34.16±1.33 (HVC-G), 22.90±0.85% (CH-G). PVF in the SH-G was 12.03±0.50, in the HVC-G it was 10.60±0.58, in the CH-G it was 7.06±0.28%. LDL: 3.73±0.13 (SH-G), 3.02±0.14 (HVC-G), 2.35±0.15 mmol/l (CH-G). TG in the SH-G - 1.87±0.11, in the HVC-G - 1.48±0.22, in the CH-G - 0.80±0.04 mmol/l. Conclusion. The highest rates of both biochemical and BIA are observed in patients with SH, and the lowest in the CH. To study lipid metabolism and evaluate the nutrition stare of patients with chronic liver disease, noninvasive methods such as BIA can be recommended.

Evaluation of the effectiveness of the proposed therapy on energy metabolism parameters in patients with chronic liver lesions on the background of secondary immunodeficiency state

Objective: to study the effect of a combination of azoximer bromide (AB) and human placenta hydrolysate (HPН) on metabolic processes in patients with chronic liver lesions on the background of secondary immunodeficiency. Materials and methods: 95 patients with chronic liver pathology on the background of secondary immunodeficiency (VIDS) aged 35 to 56 years were examined. The main group is 45 people, and the comparison group is 50 people. After a general clinical and bacteriological examination, all patients were subjected to the study of metabоlic processes. The assessment of metabolic disorders was carried out by the level of macroergic compounds in the hemolysate of the washed suspension of erythrocytes of patients by thin-layer chromatography. In addition to treatment with conventional methods, patients who were under observation were additionally prescribed a combination of drugs — bromine azoximer and human placenta hydrolysate. Patients of the comparison group received milk thistle preparations as a hepatoprotector and did not use any immunoactive drugs. Results: when studying the state of indicators of metabolic disorders after the completion of treatment, it was found that patients in the main group who received AB and HPН had almost complete normalization on the part of the studied indicators, which cannot be said about patients from the comparison group who received only conventional drugs in average therapeutic doses in the treatment complex. Conclusions: from the data obtained, it is possible to judge the positive effect of AB and HPН on the indicators of the state of energy homeostasis and consider it pathogenetically justified and clinically promising to include their combination in the complex of treatment of patients with CLP against the background of VIDS.

Prognostic mathematical models of the development of chronic non-viral liver diseases

Chronic non-viral liver diseases are one of the most pressing problems of modern internal medicine. Over the past two decades, there has been a steady increase in diseases of this group due to the widespread prevalence of major risk factors, such as obesity, diabetes mellitus, physical inactivity, alcohol abuse, irrational use of medications, etc. Since most of the patients represent the most able-bodied and active part of the population, this circumstance inevitably leads to significant financial, economic and humanitarian losses, which gives the problem acute social significance. The purpose of the study. To develop mathematical prognostic models of the development of the most common chronic non-viral liver pathology using the most important predictors of these diseases. Material and methods. The contingent included in the study consisted of 412 young and middle-aged men, 138 of them with non-alcoholic fatty liver disease, 50 with alcoholic liver disease, 157 with alcoholic-metabolic fatty liver disease and 67 people without pathology. The subjects were measured anthropometric indicators (height, body weight, calculation of body mass index, waist circumference), determination of the type of alcohol consumption according to the AUDIT questionnaire, the level of physical activity according to the IPAQ questionnaire. In the biochemical study of blood serum, the parameters of alanine and aspartate aminotransferase, total and direct bilirubin, alkaline phosphatase, gamma-glutamyltranspeptidase, glucose, insulin, and lipid spectrum were determined. The study of the qualitative and quantitative composition of the intestinal microbiome was carried out by sowing feces on nutrient media, followed by the determination of the species of microorganisms and the assessment of their quantitative content using microscopy. Ultrasound examination of the hepatobiliary zone included measuring the main sizes of the right and left lobes of the liver, as well as identifying the main signs of diffuse liver damage. To assess steatosis and liver fibrosis, a FibroScan 530 device was used with the functions of evaluating the parameter of controlled attenuation of ultrasound and transient elastography by controlled vibration. Statistical processing and analysis of the results obtained were performed using the StatTech 2.8.8 program. Results. Mathematical prognostic models have been developed to determine the probability of developing non-alcoholic fatty liver disease, alcoholic fatty liver disease and alcoholic-metabolic fatty liver disease. All the regression models obtained were statistically significant with sensitivity and specificity of more than 90%. AUROC diagnostic accuracy values exceeded 0.9 units, which characterizes the quality of diagnostic models as excellent. Conclusions. The use of mathematical prognostic models using publicly available data from objective and laboratory research methods allows optimizing the diagnosis of chronic non-viral liver diseases.

Influenza vaccine coverage in 6months-64 years-old patients affected by chronic diseases: A retrospective cohort study in Italy

ABSTRACT At the beginning of each flu season, the Italian Ministry of Health defines the categories at higher risk of influenza complications, for which vaccination is actively and freely offered. The vaccine coverage (VC) of the influenza vaccine in subjects from 6 months to 64 years of age suffering from diseases that increase the risk of complications from influenza during the 2020–2021 season was evaluated. Our study wants to evaluate the VCs of the influenza vaccine in these subjects during the 2020/2021 season in Apulia. The digital archives relative to the Apulian population were used. A retrospective cohort study design was performed. 484,636 Apulian residents aged between 6 months and 64 years suffered from at least one chronic disease; 139,222 of 484,636 subjects received the influenza vaccine (VC: 28.7%) from October 2020 to January 2021. Considering the single comorbidities, the greatest values are found for pathologies for which major surgical interventions are planned and chronic renal failure/adrenal insufficiency patients, while the worst for chronic liver diseases and pathologies for which major surgical interventions are planned. In any case, it would seem that better VC is achieved in subjects with more than one chronic condition. Influenza vaccination must be promoted as a central public health measure, also because by reducing the burden on hospitals, it can greatly benefit the management of COVID-19 patients. Greater efforts by public health institutions must be implemented in order to achieve better VC in the target categories, including chronic patients.

Mortality of the Penza region population from diseases of the liver and biliary tract in 2021-2022

A study was made of the structure of mortality of the population of the Penza region from diseases of the liver and biliary tract in 2021-2022. Data on registered deaths were analyzed, the main cause of which was non-tumor diseases of the liver and biliary tract (excluding hepatitis B, C). Statistical calculations were carried out using the STATISTICA program. Between April 2021 and April 2022, 285 deaths from diseases of the liver and biliary tract were identified. The proportion of the male population prevails over the female and is 57.5%. The largest number of deaths occurs in persons aged 45 to 59 years, the smallest - in people over the age of 90 years. There were no deaths from diseases of the liver and bile ducts among minors. Among the initial causes of death in the studied sample, cirrhosis of the liver (K74.6) is in the lead - 75.4%, in second place are gallbladder stones with acute cholecystitis (K80.0) - 4.9%, then - chronic hepatitis (K73.8) - 4.2%. The categories of the population that are at risk for mortality from diseases of the liver and biliary tract have been identified. Among males, the risk group is people aged 45-59 years, among women - 18-44 years. The risk of death among men is 14% higher than among women. The most likely cause of death is cirrhosis of the liver (the terminal stage of chronic liver pathology).

Pathophysiology of hepatic insufficiency

The liver is a unique and complex functioning organ, which is central in the metabolism of proteins, carbohydrates, fats and plays an important role in digestion, hematopoiesis, hemocoagulation, and detoxification processes. The pathology of the liver is complex and diverse, often accompanied by the pathology of other organs. Liver diseases are often encountered by doctors of various specialties, and for the clinician, knowledge of this pathology of this organ is essential. Currently, there is a steady increase in the number of patients with liver diseases, mostly people of working age. The development of acute and chronic liver pathology in the vast majority of cases is accompanied by the occurrence of various complications, up to the appearance of liver failure. The lecture contains up-to-date information about the etiology and pathogenesis of hepatic pathology. Pathological processes in the liver are considered taking into account the complexity of its structural and functional organization. The main symptoms and syndromes of liver pathology are described, their pathophysiological assessment is given. Modern classifications of jaundice, hepatitis, liver failurea regiven.

Connexin-Based Channels in the Liver.

Connexin proteins oligomerize in hexameric structures called connexin hemichannels, which then dock to form gap junctions. Gap junctions direct cell-cell communication by allowing the exchange of small molecules and ions between neighboring cells. In this way, hepatic gap junctions support liver homeostasis. Besides serving as building blocks for gap junctions, connexin hemichannels provide a pathway between the intracellular and the extracellular environment. The activation of connexin hemichannels is associated with acute and chronic liver pathologies. This article discusses the role of gap junctions and connexin hemichannels in the liver. © 2022 American Physiological Society. Compr Physiol 12:1-17, 2022.

The efficacy of drug resistant tuberculosis treatment in patients with different comorbidity status

Introduction. The efficacy of multidrug resistant (MDR) and extensive drug resistance (XDR) tuberculosis (TB) therapy is not yet resolved up to now. New regimens including tioureidoiminomethylpyridinium perchlorate (Tpp) and bedaquiline (Bq) can improve the efficacy of treatment, but due to the growing comorbidities and lack of comprehensive assessment of their severity it is difficult to define the impact of such comorbidities on the efficacy of treatment in this cohort of patients. Ма-terials and methods. Retrospective study has been conducted to review the efficacy of therapy in MDR and XDR TB patients from 18 years of age and with bacteri-al excretion (n=303), who received therapy from 2016 tо 2019. Patients were divided into two main groups: Group I — patients with MDR TB (n=153); Group II — pa-tients XDR TB (n=150). Statistical analysis of the results was carried out via Statistica 10.0 and SPSS 16.0 & Graph-Pad Prism 6 software. Spearman’s correlation coefficient was applied, with meaningful p≤0.05. Results. Theeffi-cacy of therapywas statistically significant higher in MDR TB patients (66.7% vs 40.7%, where χ2=20.6, р<0.01), meanwhile XDR TB patients on the background of low efficacy of treatment show significantly high percent of defaulted treatment (16.7% vs 3.9%, where χ2=13.4, р<0.01). Comorbidity impacts of therapy in XDR TB pa-tients’ treatment especially chronic liver pathology and gastrointestinal diseases (GIT). However, applying Tpp and Bq in scheme of therapy, the treatment outcomes in XDR TB patients with Charlson comorbidity index (ChI) from 3 to 4 improved in 44,8 и 41,1% of cases respec-tively. Conclusions. XDR TB patients are the most severe group of patients in terms of comorbidities that contrib-ute to the low efficacy of treatment. Applying of Tpp and Bq in scheme of therapy allows to efficacy of treatment in 44,8 и 41,1% of cases respectively in severe comorbid-ity patients. It is recommended to use in scheme of ther-apy new anti-TB drugs (Tpp and Bq) after examination of chronic liver pathology and GIT diseases.

Ablation of Tumor Necrosis Factor Alpha Receptor 1 Signaling Blunts Steatohepatitis in Peroxisome Proliferator Activated Receptor α-Deficient Mice.

Tumor necrosis factor -alpha (TNFα) is strongly associated with fatty liver disease (i.e, hepatosteatosis). Cytokine production has been thought of as a consequence of hepatic lipid accumulation which becomes a critical factor in the development of chronic liver pathologies as well as insulin resistance. The purpose of this study was to test the hypothesis that TNFα directly regulates lipid metabolism in liver in the mutant peroxisome-proliferator activated receptor-alpha (PPARα-/-) mouse model with robust hepatic lipid accumulation. At 10 weeks of age, TNFα and TNF receptor 1 expression are increased in livers of PPARα-/- mice compared to wild type. PPARα-/- mice were then crossed with mice lacking the receptor for TNFα receptor 1 (TNFR1-/-). Wild type, PPARα-/-, TNFR1-/-, PPARα-/- x TNFR1-/- mice were housed on ad-libitum standard chow diet for up to 40 weeks. Increases in hepatic lipid and liver injury and metabolic disruption associated with PPARα ablation were largely blunted when PPARα-/- mice were crossed with TNFR1-/- mice. These data support the hypothesis that TNFR1 signaling is critical for accumulation of lipid in liver. Therapies that reduce pro-inflammatory responses, namely TNFα, could have important clinical implications to reduce hepatosteatosis and progression of severe liver disease.

Diagnosis of liver fibrosis: an emphasis on elastography

In the strategy of managing patients with chronic diffuse liver diseases, the priority areas are the determination of the diagnosis with the determination of the main risk factors, the activity of the process (steatosis, steatohepatitis), as well as the degree of fibrous transformation. The rate of progression of liver fibrosis is a decisive factor that will determine the prognosis, treatment tactics and the likelihood of severe complications. The “gold standard” for diagnosing chronic liver pathology is a puncture liver biopsy with morphological examination of the liver tissue. At the same time, potential complications, contraindications to the procedure, low patient compliance, as well as errors in the interpretation of the results obtained due to various reasons are significant limitations of this diagnostic method. These shortcomings were the reason for the search for reliable non-invasive methods for diagnosing liver fibrosis both during the initial examination and during subsequent monitoring in dynamics. Modern methods of liver elastography are widely used for non-invasive assessment of fibrosis, demonstrating good diagnostic capabilities and significantly reducing the need for liver biopsy. Various elastography methods, which have their own advantages and disadvantages, effectively complement each other, which is successfully used in clinical practice in the diagnosis of fibrous transformation. The combined use of elastographic methods and commercial predictive diagnostic panels will increase the diagnostic accuracy in the determination of liver fibrosis.

Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment.

Liver cancer is a leading cause of death worldwide, and hepatocellular carcinoma (HCC) is the most frequent primary liver tumour, followed by cholangiocarcinoma. Notably, secondary tumours represent up to 90% of liver tumours. Chronic liver disease is a recognised risk factor for liver cancer development. Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration. The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota, its metabolites and the liver through the portal flow. The interplay between the immune system and gut microbiota is also well-known. Although primarily resulting from experiments in animal models and on HCC, growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours. Despite the curative intent of “traditional” treatments, tumour recurrence remains high. Therefore, microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment. Furthermore, microbiota could represent a non-invasive biomarker for early liver cancer diagnosis. This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development, focusing on the potential therapeutic implications.